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A fundamental understanding of the design of polymer ligands of proximal enzymes is essential for the precise targeting of cancer cells, but it is still in its infancy. In this study, we systematically investigated the contribution of the chain length, ligand density, and ligand ratio of proximal enzyme-targeted polymers to the efficacy, synergy, and selectivity for the inhibition of cancer cell proliferation. The results revealed that employing a moderate chain length as a scaffold allowed for an intrinsically high efficacy and synergy of proximal enzyme-targeted polymers, in contrast to single enzyme-targeted polymers that prefer longer chain length for efficacy. The synergy obtained in proximal enzyme targeting was not provided by the combination of the corresponding small molecules. Moreover, the maturation of the synergistic efficacy of the proximal enzyme-targeted polymers also improved selectivity. This study proposes a rational design for polymer inhibitors and/or ligands for cancer cells with a high efficacy and selectivity.

We herein report a case of bacterial meningitis and bacteremia in a 3-month-old boy caused by Streptococcus pneumoniae serotype 35B multidrug resistance. Intravenous ampicillin was administered on admission. However, when pneumococcal meningitis was suspected, the antibiotic treatment was changed to ceftriaxone (CTRX) and vancomycin (VCM). However, owing to difficulties in achieving sufficient serum trough levels of VCM, this treatment was again switched to linezolid (LZD). The patient recovered without complications after 16 days of CTRX and LZD treatment. This case suggests that LZD is a viable treatment option for bacterial meningitis.

Oral frailty (OF) is a form of frailty. Laughter and social communication such as talking and participating in community activities, contribute to extending healthy life expectancy by reducing stress and increasing physical activity. However, limited research exists on the association between laughter and social communication and OF. This cross-sectional study aimed to explore the association of laughter and social communication with the risk of developing OF using the eight-item OF Index among Fukushima residents. In 2020-2021, 916 residents aged 60-79 were surveyed regarding OF and psychosocial factors. Binomial logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for psychosocial factors associated with the OF prevalence. The OF prevalence was 41.5%. The sex- and age-adjusted ORs (95% CIs) for psychosocial factors associated with OF prevalence were 0.38 (0.26-0.57) for daily laughter, 0.51 (0.35-0.76) for laughter 1-5 times/week, 0.42 (0.20-0.89) for daily talking, 0.40 (0.22-0.72) for participating in community activities more than once/week, and 0.29 (0.20-0.43) for no depressive symptoms. After multivariate adjustment, only daily laughter and no depressive symptoms were associated with OF. As a public health strategy, increasing laughter and social communication frequencies, along with reducing depressive symptoms, may enhance healthy life expectancy through improved frailty., (© 2024. The Author(s).)

Background: The incidence of pancreatic cancer is on the rise, and its prognosis remains poor. Recent reports have established a link between the gut and oral microbiome and pancreatic cancer. However, the intricacies of this association within the Japanese population remain unclear. In this study, we investigated the gut and oral microbiomes of Japanese patients with pancreatic cancer, comparing them with those of healthy individuals., Methods: We recruited 30 patients with untreated pancreatic cancer and 18 healthy controls at Kyoto University Hospital (2018-2022). We performed a comprehensive 16S rRNA gene sequencing to analyze their gut and oral microbiomes., Results: Analysis revealed that the diversity of the gut and oral microbiomes of patients with pancreatic cancer was reduced compared to that of the healthy controls. Specifically, we observed an increase in the genus Streptococcus in both the gut and oral microbiomes and a significant decrease in several butyrate-producing bacteria in fecal samples. Moreover, bacteria such as Streptococcus mitis and Holdemanella biformis were present in pancreatic cancer tissues, suggesting that they might influence the carcinogenesis and progression of pancreatic cancer., Conclusions: The gut and oral microbiome differed between patients with pancreatic cancer and healthy controls, with a notable decrease in butyrate-producing bacteria in the gut microbiome of the patients. This suggests that there may be a distinct microbial signature associated with pancreatic cancer in the Japanese population. Further studies are required to elucidate the microbiome's causal role in this cancer and help develop prognostic markers or targeted therapies., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: To evaluate the efficacy and safety of oral semaglutide for type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)., Materials and Methods: This was a single-arm, multicentre, prospective study. Among 80 consecutive patients with MASLD and T2DM who newly received oral semaglutide, 70 completed 48-week oral semaglutide treatment as scheduled and were included in an efficacy analysis. Dose adjustments of oral semaglutide were determined by each physician while monitoring efficacy and adverse events., Results: Significant improvements in body weight, liver enzymes, lipid profile, and glycaemic control were found at 48 weeks compared with baseline values (all p < 0.01). Controlled attenuation parameter values significantly decreased from baseline to 48 weeks (p < 0.01). Changes in alanine aminotransferase concentrations (r = 0.37, p < 0.01) and controlled attenuation parameter values (r = 0.44, p < 0.01) were significantly correlated with changes in body weight. Liver fibrosis markers, such as type IV collagen 7S, Wisteria floribunda agglutinin-positive Mac-2-binding protein, fibrosis-4 index, and liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.01). The most common adverse events were Grades 1-2 transient gastrointestinal symptoms, such as nausea (23 patients, 28.8%), dyspepsia (12, 15.0%) and appetite loss (4, 5.0%)., Conclusions: Oral semaglutide treatment for T2DM in patients with MASLD leads to an improvement in liver steatosis and injury, surrogate markers of fibrosis, diabetic status, and lipid profile, and reduces body weight., (© 2024 John Wiley & Sons Ltd.)

Background: This study aimed to examine postoperative recurrence after curative pancreatic resection following neoadjuvant chemoradiotherapy (NACRT) in patients with resectable (R-) and borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC), focusing on its relationship with the standardized uptake value (SUV) on 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET)., Method: The postoperative initial recurrence patterns were examined in patients with R- and BR-PDAC who underwent NACRT followed by curative pancreatic resection. Data collected from three prospective clinical trials were retrospectively analysed., Results: After a median follow-up of 29 months, 91 (60 %) of 151 patients experienced postoperative recurrence. The median recurrence-free survival (RFS) for all patients was 18 months. The sites of first recurrence were lung-only in 24 (26 %) patients, liver-only in 23 (25 %), local-only in 11 (12 %), peritoneum-only in 10 (11 %), other single site in 5 (5 %), and multiple sites in 19 (21 %) patients. Multivariate analysis identified the maximum standardized uptake value (SUVmax) on FDG-PET at diagnoses ≥5.40 (hazard ratio [HR], 1.62; 95 % confidence interval [CI], 1.01-2.61; p = 0.045) and node-positive pathology (HR, 2.01; 95 % CI, 1.32-3.08; p = 0.001) as significant predictors of RFS. Furthermore, the SUVmax at initial diagnosis and after NACRT correlated with liver metastasis., Conclusion: R- and BR-PDACs with high SUV on FDG-PET at diagnosis are risk factors for postoperative recurrence. Among patients who undergo surgery after NACRT, those with a high SUVmax at diagnosis or post-NACRT require careful attention for postoperative liver recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Polymer self-assemblies driven by enthalpic interactions, such as hydrogen bonding and electrostatic interactions, exhibit distinct properties compared to those driven by hydrophobic interactions. Carbohydrate-carbohydrate interactions, which are observed in physiological phenomena, also fall under enthalpic interactions. Our group previously reported on self-assemblies of methacrylate-type glycopolymers carrying mannose units in the presence of calcium ions; however, a detailed study of these interactions was lacking. In this work, we investigated the interactions between glycopolymers using the quartz crystal microbalance (QCM) method. Our quantitative analysis revealed that the interactions between the glycopolymers were influenced by the carbohydrate structures in the side chains, the types of divalent metal ions, and the structures of the polymer main chains. Notably, the strongest interaction was observed in the combination of methacrylate-type glycopolymers carrying mannose units and calcium ions, demonstrating their potential as a driving force for polymer self-assembly.

Background: Stage B heart failure (HF) refers to structural heart disease without signs or symptoms of HF, so that early intervention may delay or prevent the onset of overt HF. However, stage B HF is a very broad concept, and risk stratification of such patients can be challenging., Methods and Results: We conducted a prospective study of data for 1646 consecutive patients with HF from the KUNIUMI (Kobe University Heart Failure Registry in Awaji Medical Center) registry chronic cohort. The definition of HF stages was based on current guidelines for classification of 29 patients as stage A HF, 761 as stage B HF, 827 as stage C HF, and 29 patients as stage D HF. The primary end point was the time-to-first-event defined as cardiovascular death or HF hospitalization within 2.0 years of follow-up. A maximum of 6 adjustment factor points was assigned based on Cox proportional hazards analysis findings for the hazard ratio (HR) of independent risk factors for the primary end point: 1 point for anemia, estimated glomerular filtration rate <45 mL/min per 1.73 m 2 , brain natriuretic peptide ≥150 pg/mL, and average ratio of early transmitral flow velocity to early diastolic mitral annular velocity >14, and 2 points for clinical frailty scale >3. Patients with stage B HF were stratified into 3 groups, low risk (0-1 points), moderate risk (2-3 points), and high risk (4-6 points). Based on this scoring system (BEEAF 2 [brain natriuretic peptide, estimated glomerular filtration rate, ratio of early transmitral flow velocity to early diastolic mitral annular velocity, anemia, and frailty]), the outcome was found to become worse in accordance with risk level. High-risk patients with stage B HF and patients with stage C HF showed similar outcomes., Conclusions: Our scoring system offers an easy-to-use evaluation of risk stratification for patients with stage B HF.

Background: Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers., Methods: We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort., Results: The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%)., Conclusions: We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer., (© 2024. The Author(s).)

Background: We investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years old with moderate-to-severe atopic dermatitis not adequately controlled with existing therapies., Methods: In this randomized, double-blind, phase 3 study, patients received dupilumab (n = 30) or placebo (n = 32) with concomitant topical corticosteroids for 16 weeks, then all patients received dupilumab from 16 to 52 weeks. The primary endpoint was the proportion of patients with ≥75% improvement in Eczema Area and Severity Index (EASI) score from baseline (EASI-75) to Week 16. Key secondary endpoints included changes in EASI score, proportion of patients with investigator global assessment (IGA) scores of 0/1, and changes in worst daily itch numerical rating scale (NRS) scores (evaluated in patients aged ≥6 to <12 years [n = 35])., Results: At Week 16, more patients achieved EASI-75 with dupilumab than placebo (43.3% vs 18.8%; P = 0.0304), and the least squares mean (LSM) difference in percent change in EASI scores at Week 16 of dupilumab vs placebo was -39.4% (P = 0.0003). However, no significant difference in the proportion of patients achieving IGA scores of 0/1 at Week 16 with dupilumab versus placebo were seen (10.0% vs 9.4%; P = 0.8476). The percent change in worst daily itch NRS scores at Week 16 was higher with dupilumab (LSM difference: -33.3%; nominal P = 0.0117). Dupilumab was well tolerated; no new safety signals were identified., Conclusions: Dupilumab showed consistent efficacy and was well tolerated in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis previously insufficiently controlled with existing therapies., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: The semitendinosus tendon is one of the most used autografts in anterior cruciate ligament reconstruction. Although recent evidence indicates that young patients, especially in females, may experience high rates of revision and residual instability, the reasons for the inferior outcomes in these patients remain unclear. To address this issue, we aimed to compare the mechanical properties of the semitendinosus tendon used for anterior cruciate ligament reconstruction in male and female patients of various ages., Methods: The semitendinosus tendons harvested from 31 male and 29 female patients who underwent anterior cruciate ligament reconstruction surgery using the semitendinosus tendon autografts were used in this study. Using the distal part of the harvested semitendinosus tendon, the extent of cyclic loading-induced elongation (i.e., the extent of the increase in slack length) and the Young's modulus were measured during cyclic tensile testing., Findings: Spearman correlation analyses revealed that the Young's modulus (|ρ| = 0.725, P < 0.001), but not elongation (|ρ| ≤ 0.036, P ≥ 0.351) positively correlated with the patient age in male tendon samples. In contrast, for female tendon samples, the elongation (|ρ| ≥ 0.415, P ≤ 0.025), but not the Young's modulus (|ρ| = 0.087, P = 0.655) negatively correlated with the patient age., Interpretation: These results indicate that the semitendinosus tendon used for anterior cruciate ligament reconstruction in young male patients is compliant, whereas that in young female patients is susceptible to elongation induced by cyclic loading., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A 31-year-old Japanese man presented with cerebral and pulmonary cryptococcosis. Cryptococcus gattii (C. gattii) genotype VGIIb was detected in the patient's sputum and cerebrospinal fluid specimens. The serum levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies were elevated in this patient, which has been associated with pulmonary alveolar proteinosis and is considered a risk factor for C. gattii infection. After undergoing >12 months of antifungal treatments, the patient showed improvements in symptoms and findings on brain and lung imaging. Several Japanese patients who develop C. gattii infection have also been reported; however, most of these patients have been infected outside Japan, as C. gattii infection is rare in Japan. Only one patient with C. gattii genotype VGIIb infection has been reported in Japan, and it is believed that this patient contracted the infection in China. In the present case, our patient has never been outside Japan, indicating that the infection originated in Japan. Our findings suggest that C. gattii might be spreading in Japan. Therefore, patients with positive serum anti-GM-CSF antibodies should be thoroughly monitored for C. gattii infection, even those living in Japan., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Left atrial (LA) plication is a procedure used to correct an LA that expands posteriorly due to remodeling. This study aimed to determine the efficacy of additional LA plication in reducing postoperative cardiovascular events (CVEs) after mitral valve (MV) repair in atrial functional mitral regurgitation (MR) patients., Methods: Between October 2008 and August 2023, MV repair with or without LA plication in 74 patients was studied. This study examined the efficacy of concomitant LA plication during MV repair., Results: All patients underwent mitral annuloplasty. Of these, 26 underwent additional LA plication. In the mid-term periods, protruding posterior LA length in patients with LA plication was shorter than those without LA plication (2.8±0.49 vs . 3.3±0.72 cm, P=0.01). The percentage change in aortomitral angle from preoperative to mid-term periods in patients with LA plication was bigger than those without LA plication (1.04°±0.102° vs . 0.98°±0.084°, P=0.01). Posterior leaflet coaptation angle in patients with LA plication was smaller than those without LA plication (42°±15° vs . 76°±30°, P<0.001). A postoperative posterior leaflet coaptation angle of 101° had the maximum sum of sensitivity and specificity in predicting postoperative CVEs (96.9% and 76.9%, respectively). Patients with a postoperative posterior leaflet coaptation angle of 101° or higher had a poorer prognosis than those with an angle less than 101°, with an event-free rate of 18% vs . 80% at 7 years after surgery (P<0.0001)., Conclusions: Additional LA plication might be useful in reducing postoperative CVEs in atrial functional MR patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-593/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Extracellular hydrolysis of the phosphate esters of B vitamins (B1, B2, and B6) is crucial for their cellular uptake and metabolism. Although a few zinc-dependent enzymes have been implicated in these processes, their exact mechanisms of action remain largely unknown. This study investigated the potential involvement of phosphate group hydrolyzing enzymes in the hydrolysis of B vitamin phosphate esters. We evaluated enzyme activity in membrane lysates prepared from cells transiently transfected with these enzymes or those endogenously expressing them. Specifically, we investigated how zinc deficiency affects the rate of hydrolysis of B vitamin phosphate esters in cellular lysates. Assessment of the activities of zinc-dependent ectoenzymes in the lysates prepared from cells cultured in zinc-deficient conditions and in the serum of rats fed zinc-deficient diets revealed that zinc deficiency reduced the extracellular hydrolysis activity of B vitamin phosphate esters. Furthermore, our findings explain the similarities between several symptoms of B vitamin and zinc deficiencies. Collectively, this study provides novel insights into the diverse symptoms of zinc deficiency and could guide the development of appropriate clinical strategies., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Objective: Quantifying and managing the matches and training loads of players is important for injury prevention. As rugby union is a full-contact sport and frequent contact injuries occur, it might also be important to quantify and manage players' contact loads. This study aimed to clarify the relationship between contact load and injury incidence in elite rugby union players., Methods: Forty-eight elite rugby union players (27.0 ± 3.5 years) in Japan were monitored during one season (8 months). The contact load, an index of training load, was evaluated as collision count and collision load measured using a global positioning system device, and then calculated using the acute:chronic workload ratio (ACWR) based on the exponentially weighted moving average (EWMA). The association between the EWMA-ACWR of contact load and injury incidence was analyzed using generalized estimating equations., Results: Of the 58 injuries during one season, 70.7% were contact injuries. Collision counts and collision load calculated by EWMA-ACWR were associated with the risk of injury ( p  < 0.01 both), with the odds ratios were 4.20 [95% confidence interval (CI): 1.74-10.11] and 4.44 (95% CI: 1.95-10.13), respectively., Conclusion: Contact load calculated using EWMA-ACWR was associated with injury in elite rugby union players., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Iwasaki, Someya, Nagao, Nozu, Shiota and Takazawa.)

Aim: The unique feature of Fontan circulation is elevated central venous pressure, which causes Fontan-associated liver disease (FALD). FALD is associated with a high incidence of hepatocellular carcinoma (HCC). Performing biopsies in patients with FALD is difficult as a result of warfarinization; gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), a noninvasive examination, is useful for characterizing liver disease and detecting HCC. However, few studies have reported the detailed features of Gd-EOB-DTPA MRI, and the association between these findings and prognosis. Thus, this study aimed to investigate the utility of Gd-EOB-DTPA MRI to predict HCC development in patients with FALD., Methods: This study enrolled 44 patients with FALD (mean age 25 years) who underwent Gd-EOB-DTPA MRI. The hepatobiliary phase images were scored semiqualitatively, and the patients were classified into the mild (0-1 point) or severe group (≥2 points). The endpoint was HCC, and event-free survival was analyzed using Kaplan-Meier and log-rank tests., Results: The severe group included 19 patients. During a mean follow-up of 58 months, HCC developed in six patients. Kaplan-Meier analysis revealed that patients in the severe group had a significantly poorer prognosis than those in the mild group (p = 0.0053). The Fibrosis-4 index and liver-to-spleen ratio of patients with HCC were moderate., Conclusions: Gd-EOB-DTPA MRI can be used to classify disease severity and predict the prognosis of patients with FALD., (© 2024 Japan Society of Hepatology.)

Background: The coronary sinus type of atrial septal defect is rare. Standard treatment typically involves intracardiac repair using conventional sternotomy or thoracotomy incisions; however, robotic technology can offer a feasible alternative due to its ability to provide a high-quality surgical view of this anomaly., Case Presentation: A 72-year-old man presented with asymptomatic atrial septal defect. Echocardiography revealed a direct communication between the left atrium and CS with left-to-right shunt flow and a Qp/Qs ratio of 2.1:1. The coronary sinus type of atrial septal defect was indicated for the totally endoscopic robotic repair considering few comorbidities. We present a successful robotic repair of coronary sinus atrial septal defect with concomitant tricuspid annuloplasty via the right atrium, properly identifying the boundary between the mitral annulus and coronary sinus through a high-quality surgical view., Conclusion: Robotic repair can serve as a viable and therapeutically effective alternative for cases of coronary sinus atrial septal defect with concomitant tricuspid annuloplasty., (© 2024. The Author(s).)

Objectives: This 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., Methods: From 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., Results: The 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., Conclusions: Preoperative 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Takahashi, Morisaki, Sakon, Nishiya, Inno, Kawase, Nishimoto, Nagao, Kishimoto, Noda and Shibata.)

Aim: The Fukushima Daiichi Nuclear Power Plant accident caused lifestyle changes and psychological distress in residents living near the plant. This study clarified the associations between changes in residents' lifestyles and psychological factors with the onset of metabolic syndrome (METs) after the accident., Methods: This longitudinal study included 10,373 residents who underwent the Comprehensive Health Check and Mental Health and Lifestyle Survey in Fiscal Year (FY) 2013. Follow-up surveys were conducted between FY 2014 and FY 2017. Lifestyle changes and the METs incidence were evaluated using a logistic regression model., Results: METs developed in 14.0% of subjects. In addition to metabolic factors, such as the body mass index, hypertension, dyslipidemia, and diabetes mellitus, there were differences in physical activity, fast walking, eating fast, eating habits before bedtime, skipping breakfast, current smoking, and alcohol intake between subjects with and without new-onset METs. Eating fast, current smoking, and drinking alcohol were positively associated with new-onset METs, whereas starting physical activity and fast walking were inversely associated with new-onset METs., Conclusions: Disaster-related lifestyle changes, such as eating fast, starting to smoke, and continued alcohol intake, were risk factors for new-onset METs after the Fukushima Daiichi Nuclear Power Plant accident.

Background: Sacubitril/valsartan (SV) is recommended for patients with heart failure (HF). In addition, a combination of 4 HF medications, including SV, is recommended in patients with HF with reduced ejection fraction (HFrEF). However, evidence on the characteristics of patients who could continue SV and its initiation methods is limited., Objective: To investigate the factors associated with SV continuation and methods of combining HF medications., Methods: This retrospective cohort study included HF patients who initiated with SV at our institution. The endpoint was SV continuation for 6 months after its initiation. Multivariate analysis was used to extract factors associated with SV continuation. The relationship between the methods of combining HF medications (renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, or sodium-glucose cotransporter 2 inhibitors), including the number of HF medications, their combination patterns, and the timing of their initiation, and SV continuation was examined in patients with HFrEF., Results: Of 186 eligible patients, 68.8% had HFrEF, and 79.0% continued SV for 6 months. Significant factors associated with SV continuation were albumin ≥ 3.5 g/dL (odds ratio, 4.81; 95% confidence interval, 2.19-10.59), body mass index (BMI) ≥ 18.5 kg/m 2 (4.17; 1.10-15.85), and systolic blood pressure (SBP) ≥ 110 mmHg (2.66; 1.12-6.28). In patients with HFrEF, the proportion of HF medications not initiated simultaneously with SV was significantly higher in the continuation group than in the discontinuation group (67.3% vs 33.3%, P = 0.002). The number of HF medications and their combination patterns were not significantly associated with SV continuation., Conclusion and Relevance: Albumin, BMI, and SBP are useful indicators for selecting patients who are likely to continue SV. In addition, initiating only SV without simultaneously initiating other HF medications in patients with HFrEF may lead to SV continuation., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The pathophysiology of variant transthyretin (TTR) amyloidosis (ATTRv) is associated with destabilizing mutations in the TTR tetramer. However, why TTR with a wild-type genetic sequence misfolds and aggregates in wild-type transthyretin amyloidosis (ATTRwt) is unknown. Here, we evaluate kinetic TTR stability with a newly developed ELISA system in combination with urea-induced protein denaturation. Compared with that in control patients, endogenous TTR in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) exhibited thermodynamic instability, indicating that circulating TTR instability may be associated with the pathogenesis of ATTRwt as well as ATTRv. Our findings provide new insight into the underlying mechanisms of ATTRwt., (© 2024. The Author(s).)

Cyclic polymers, which are found in the field of biopolymers, exhibit unique physical properties such as suppressed molecular mobility. Considering thermodynamics, the suppressed molecular mobility of cyclic polymers is expected to prevent unfavorable entropy loss in molecular interactions. In this study, we synthesized cyclic glycopolymers carrying galactose units and investigated the effects of their molecular mobility on the interactions with a lectin (peanut agglutinin). The synthesized cyclic glycopolymers exhibited delayed elution time on size exclusion chromatography and a short spin-spin relaxation time, indicating typical characteristics of cyclic polymers, including smaller hydrodynamic size and suppressed molecular mobility. The hemagglutination inhibition assay revealed that the cyclic glycopolymers exhibited weakened interactions with peanut agglutinin compared to the linear counterparts, attributable to the suppressed molecular mobility. Although the results are contrary to our expectations, the impact of polymer topology on molecular recognition remains intriguing, particularly in the context of protein repellent activity in the biomedical field., (© 2024 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

Background: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis., Methods: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019., Results: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis., Conclusion: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents., Competing Interests: Declaration of Competing interest Tokimatsu I. received scholarship donations from Shionogi Pharmaceuticals, Inc. and Daiichi Sankyo Co. Ltd. Ukimura A. received scholarship donations from Shionogi Pharmaceuticals, Inc. Hiroshige Mikamo received speaker honoraria from MSD K.K., FUJIFILM Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Shionogi & Co., Ltd. Japan, Kowa Co. Ltd., Gilead Sciences K.K., GSK Group of Companies, Saraya Co. Ltd., Tsumura & Co. Japan, Nippon Becton Dickinson Company, Ltd., and FUKOKU Co., Ltd., grant supports from Asai Kasei Pharma Co., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., and FUKOKU Co., Ltd. Mitsutake K, Shinya N, Seki M, Ohara T, Uemura K, Fukunaga M, Sakai J, Nagao M, Sata M, Hamada Y, Kawasuji H, Yamamoto Y, Nakamatsu M, Koizumi Y, Aoyagi T, Sawai T, Tanaka T, Izumikawa K, Takayama Y, Nakamura K, Kanemitsu K, Nakajima K, and Akine D have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population., (© 2024 The Author(s). Microbiology and Immunology published by The Societies and John Wiley & Sons Australia, Ltd.)

Background: Thyroid ultrasound examinations using a cohort study design (from the Fukushima Health Management Survey [FHMS]) were conducted after the nuclear power plant accident caused by the Great East Japan Earthquake in 2011. This study investigated the association between radiation exposure and the detection of thyroid cancer in children and adolescents., Methods: The cohort study has been conducted in Fukushima prefecture in Japan since 2011. The primary outcome was the external dose. We enrolled 253346 examinees who lived in Fukushima at the time of the accident (Dataset A), including 113120 examinees who had data on external radiation exposure (ERE) (Dataset B). The median dose in the examinee's district was used for missing dose. The association between ERE and detection of thyroid cancer or suspected thyroid cancer was analyzed using Poisson regressions with two types of explanatory variables: sex, age, overweight status, and district (Model 1), and past medical history, family history of thyroid cancer, frequency of seafood consumption, and frequency of seaweed consumption in addition to Model 1 (Model 2)., Findings: During the second and third rounds of examinations, a total of 97 thyroid patients were detected, for a detection rate of 10.328 [ 10 5 year - 1 ] (95% confidence interval: 8.464-12.602 [ 10 5 year - 1 ]). Multivariate Poisson regression showed that the detection rate ratio of the ERE (1+ mSv) to <1 (mSv) was 1.577 (0.715-3.394) in Model 1 and 1.596 (0.726-3.512) in Model 2, for Dataset A; and 1.677 (0.746-3.773) in Model 1 and 1.669 (0.743-3.748) in Model 2, for Dataset B., Interpretation: Our study showed no association between radiation exposure with extremely low dose which were more than 99.9% of all the exposure was less than 5 mSv, and thyroid cancer detection, when the follow-up period was an average of 3.7 years at the present, using the cohort study design., Funding: The National Health Fund for Children and Adults Affected by Nuclear Incidents in Japan., Competing Interests: The study was supported by grants from the National Health Fund for Children and Adults Affected by the Nuclear Incident., (© 2024 The Authors.)

The 88 th Annual Scientific Meeting of the Japanese Circulation Society (JCS2024) was held from Friday, March 8 th to Sunday, March 10 th in Kobe, Japan. The main theme of this 3-day meeting was "The Future of Cardiology: Challenges in Overcoming Cardiovascular Disease". As COVID-19 has been finally conquered, with revision of its categorization under the Infectious Disease Control Law and relaxation of infection prevention measures, it was once again possible to have face-to-face presentations and lively discussion. JCS2024 was a major success, with 19,209 participants and attendees, thanks to the greatly appreciated cooperation and support from all affiliates.

Background: This study evaluated right ventricular (RV) volume, strain, and morphology using cardiac 4-dimensional computed tomography (4D-CT) to detect pulmonary hypertension (PH) in adults with repaired tetralogy of Fallot (TOF) scheduled for transcatheter pulmonary valve implantation (TPVI)., Methods and Results: Using cardiac 4D-CT data, we calculated RV strain in 3 different geometries and RV outflow tract (RVOT) mass in 42 patients with repaired TOF. We compared RV strain and RVOT mass between patients with and without PH. Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance of these measurements for identifying PH. Four-chamber (4ch) strain was significantly smaller for patients with (n=10) than without (n=32) PH (8.8±1.7% vs. 11.1±2.4%, respectively; P<0.01), whereas RVOT mass was significantly larger in the PH group (12.5±3.5 vs. 9.2±3.2 cm 2 ; P<0.01). ROC analysis of the diagnostic performance revealed that the respective sensitivity and specificity was 70% and 84% (area under the curve [AUC]=0.784) for 4ch strain of 8.8%; 80% and 69% (AUC=0.766) for RVOT mass of 10.7 cm 2 ; and 80% and 81% (AUC=0.844) for a 4ch strain/RVOT mass ratio of 0.97., Conclusions: RVOT mass and 4ch strain obtained from cardiac 4D-CT may be helpful for identifying PH in patients with repaired TOF.

Objectives: On 18 F-Fludeoxyglucose (FDG) PET/CT, active sarcoid lesions are often difficult to differentiate from malignant lesions. We investigated the potential of the glucose metabolic rate (MR glc , mg/min/100 mL), a new quantification of glucose metabolic kinetics derived from direct reconstruction based on linear Patlak analysis, to distinguish between sarcoidosis and malignant lesions., Materials and Methods: A total of 100 patients with cardiac sarcoidosis (CS) and 67 patients with cancer who underwent four-dimensional FDG PET/CT were enrolled. The lesions with a standardized uptake value (SUV) ≥ 2.7 on the standard scan were included as active lesions in the analysis. SUV and MR glc were derived using data acquired between 30 min and 50 min on four-dimensional FDG PET/CT. The mean value in the volume of interest (size 1.5 cm 3 ) was measured. The diagnostic performance of sarcoidosis using MR glc and SUV was evaluated using receiver-operating-characteristic (ROC) analysis., Results: A total of 90 sarcoidosis lesions from 44 CS patients (18 males, 63.4 ± 12.2 years) and 87 malignant lesions from 57 cancer-bearing patients (32 males, 65 ± 14 years) were analyzed. SUV and MR glc for sarcoid lesions were significantly lower than those for malignant lesions (SUV, 4.98 ± 2.00 vs 6.21 ± 2.14; MR glc , 2.52 ± 1.39 vs 3.68 ± 1.61; p < 0.01). ROC analysis indicated that the ability to discriminate sarcoid patients from those with malignancy yielded areas under the curves of 0.703 and 0.754, with sensitivities of 64% and 77% and specificities of 75% and 72% for SUV 5.025 and MR glc 2.855, respectively., Conclusion: MR glc was significantly lower in sarcoid lesions than malignant lesions, and improved sarcoid lesions identification over SUV alone., Clinical Relevance Statement: MR glc improves sarcoid lymph node identification over SUV alone and is expected to shorten the examination time by eliminating delayed scans., Key Points: Active sarcoid lesions are sometimes associated with FDG accumulation and should be differentiated from malignant lesions. SUV and metabolic rate of glucose (MRglc) strongly positively correlated, and MRglc could differentiate sarcoid and malignant lesions. MRglc allows for accurate evaluation and staging of malignant lesions., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

The respiratory effects of particulate matter (PM) in subway station platforms or tunnels have attracted considerable research attention. However, no studies have characterized the effects of subway PM on allergic immune responses. In this study, iron oxide (α-Fe 2 O 3 and Fe 3 O 4 ) particles-the main components of subway PM-were intratracheally administered to BALB/c mice where ovalbumin (OVA) induced allergic pulmonary inflammation. Iron oxide particles enhanced OVA-induced eosinophil recruitment around the bronchi and mucus production from airway epithelium. The concentrations of type 2 cytokines, namely, interleukin (IL)-5 and IL-13, in bronchial alveolar lavage fluids were increased by iron oxide particles. Iron oxide particles also increased the number of type 2 innate lymphoid cells and CD86 + cells in the lung. Moreover, phagocytosis of particles in lung cells was confirmed by Raman spectroscopy. In a subsequent in vitro study, bone marrow-derived antigen-presenting cells (APCs) isolated from NC/Nga mice were exposed to iron oxide particles and OVA. They were also exposed to outdoor ambient PM: Vehicle Exhaust Particulates (VEP) and Urban Aerosols (UA) as references. Iron oxide particles promoted the release of lactate dehydrogenase, C-X-C motif chemokine ligand 1 and IL-1α from APCs, which tended to be stronger than those of VEP. These results suggest that iron oxide particles enhance antigen presentation in the lungs, promoting allergic immune response in mice; iron oxide particles-induced death and inflammatory response of APCs can contribute to allergy exacerbation. Although iron oxide particles do not contain various compounds like VEP, iron oxide alone may have sufficient influence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Primary ciliary dyskinesia (PCD) is a hereditary disease caused by genes related to motile cilia. We report two male pediatric cases of PCD caused by hemizygous pathogenic variants in the OFD1 centriole and centriolar satellite protein ( OFD1 ) gene. The variants were NM&#95;003611.3: c.[2789&#95;2793delTAAAA] (p.[Ile930LysfsTer8]) in Case 1 and c.[2632&#95;2635delGAAG] (p.[Glu878LysfsTer9]) in Case 2. Both cases had characteristic recurrent respiratory infections. Neither case had symptoms of oral-facial-digital syndrome type I. We identified a variant (c.2632&#95;2635delGAAG) that has not been previously reported in any case of OFD1 -PCD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Yifei Xu et al.)

Background: Tacrolimus is an immunosuppressant administered to patients undergoing lung transplantation. Itraconazole is often concomitantly used with tacrolimus to prevent fungal infections and increase tacrolimus concentration. However, the pharmacokinetics of tacrolimus in Japanese lung transplant recipients and the effect of itraconazole on its pharmacokinetics have not been adequately evaluated. Population pharmacokinetic analysis was conducted to develop an optimal dose adjustment method for use upon itraconazole initiation in Japanese lung transplant recipients., Methods: This study comprised Japanese lung transplant recipients whose blood tacrolimus and itraconazole concentrations were measured between January 2017 and December 2019. A nonlinear mixed-effects modeling program was used to explore the covariates of tacrolimus pharmacokinetics and effects of concomitant itraconazole use. Using the model, the optimal initial tacrolimus dose was calculated and a dose adjustment method comprising concomitant itraconazole use was developed., Results: A total of 1693 tacrolimus trough blood concentrations and 85 itraconazole trough plasma concentrations were obtained from 43 patients. Postoperative day, albumin level, and administration route were extracted as covariates for tacrolimus pharmacokinetics. The drug-drug interaction between tacrolimus and itraconazole could be predicted more accurately by considering the concentration-dependent inhibition of itraconazole. The optimal initial tacrolimus dose was 2.0 mg twice daily for tube and 1.5 mg twice daily for oral administration. To maintain the target concentration, the tacrolimus dose was reduced by 60% upon itraconazole initiation., Conclusions: This study is the first to use population pharmacokinetic analysis to assess the interaction between tacrolimus and itraconazole in patients who underwent lung transplantation. These results provide useful insights for optimizing the initial tacrolimus dose for concomitant itraconazole use., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Blood vessels show various COVID-19-related conditions including thrombosis and cytokine propagation. Existing in vitro blood vessel models cannot represent the consequent changes in the vascular structure or determine the initial infection site, making it difficult to evaluate how epithelial and endothelial tissues are damaged. Here, we developed a microphysiological system (MPS) that co-culture the bronchial organoids and the vascular bed to analyze infection site and interactions. In this system, virus-infected organoids caused damage in vascular structure. However, vasculature was not damaged or infected when the virus was directly introduced to vascular bed. The knockout of interferon-related genes and inhibition of the JAK/STAT pathway reduced the vascular damage, indicating the protective effect of interferon response suppression. The results demonstrate selective infection of bronchial epithelial cells and vascular damage by cytokines and also indicate the applicability of MPS to investigate how the infection influences vascular structure and functions.

Rationale and Objectives: This study investigated the use of deep learning-generated virtual positron emission tomography (PET)-like gated single-photon emission tomography (SPECT VP ) for assessing myocardial strain, overcoming limitations of conventional SPECT., Materials and Methods: SPECT-to-PET translation models for short-axis, horizontal, and vertical long-axis planes were trained using image pairs from the same patients in stress (720 image pairs from 18 patients) and resting states (920 image pairs from 23 patients). Patients without ejection-fraction changes during SPECT and PET were selected for training. We independently analyzed circumferential strains from short-axis-gated SPECT, PET, and model-generated SPECT VP images using a feature-tracking algorithm. Longitudinal strains were similarly measured from horizontal and vertical long-axis images. Intraclass correlation coefficients (ICCs) were calculated with two-way random single-measure SPECT and SPECT VP (PET). ICCs (95% confidence intervals) were defined as excellent (≥0.75), good (0.60-0.74), moderate (0.40-0.59), or poor (≤0.39)., Results: Moderate ICCs were observed for SPECT-derived stressed circumferential strains (0.56 [0.41-0.69]). Excellent ICCs were observed for SPECT VP -derived stressed circumferential strains (0.78 [0.68-0.85]). Excellent ICCs of stressed longitudinal strains from horizontal and vertical long axes, derived from SPECT and SPECT VP , were observed (0.83 [0.73-0.90], 0.91 [0.85-0.94])., Conclusion: Deep-learning SPECT-to-PET transformation improves circumferential strain measurement accuracy using standard-gated SPECT. Furthermore, the possibility of applying longitudinal strain measurements via both PET and SPECT VP was demonstrated. This study provides preliminary evidence that SPECT VP obtained from standard-gated SPECT with postprocessing potentially adds clinical value through PET-equivalent myocardial strain analysis without increasing the patient burden., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: Fungal infection after lung transplantation can lead to poor clinical outcome, for which lung transplant recipients require prophylaxis. One of the antifungal agents used after lung transplantation is nebulized amphotericin B (AMB). Nebulized AMB causes adverse events such as dyspnea and airway irritation, and long-term use leads to high economic costs. So far, prophylactic regimens employing AMB deoxycholate (AMB-d) and liposomal AMB (L-AMB) have been developed. This study compared the efficacy, safety, and cost of AMB-d and L-AMB., Patients and Methods: Patients who underwent lung transplantation at Kyoto University Hospital from January 2021 to May 2023 were included in this study. Thirty-three patients received nebulized AMB-d, whereas 29 received nebulized L-AMB., Results: Both regimens maintained comparable prophylactic efficacy regarding the development of fungal infection in the AMB-d and L-AMB groups (3.0% vs. 3.4%, P = 0.877). Patients treated with nebulized L-AMB experienced fewer respiratory-related adverse reactions than those treated with nebulized AMB-d (6.9% vs. 30.3%, P < 0.05), leading to a longer treatment duration with L-AMB than with AMB-d. Additionally, the daily cost of administering L-AMB was lower than that of administering AMB-d (3609 Japanese yen vs. 1792.3 Japanese yen, P < 0.05)., Discussion: These results suggest that nebulized L-AMB is safer and more cost-effective than nebulized AMB-d, with comparable efficacy., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background/aim: 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is reportedly associated with the malignant potential of cancer. This study aimed to evaluate the association between FDG accumulation and tumor metabolism in pancreatic ductal adenocarcinoma (PDAC)., Patients and Methods: A prognostic analysis of data from 131 patients with PDAC who underwent FDG-PET/CT before curative-intent pancreatic surgery was performed. Capillary electrophoresis-mass spectrometry (CE-MS) was used to analyze the metabolome of tumor and non-neoplastic pancreas from 80 patients. These patients were divided into two groups: low SUVmax group (SUVmax <6.09) and high SUVmax group (SUVmax ≥6.09)., Results: Carbohydrate antigen 19-9 (CA19-9), maximum standardized uptake value (SUVmax) of PET, N stage, and postoperative chemotherapy were identified as significant prognostic factors by univariate analysis. SUVmax emerged as an independent prognostic factor for overall survival [hazard ratio (HR)=1.88, p<0.05] and disease-free survival (HR=2.01, p<0.05) in multivariate analysis. Metabolic analyses confirmed that 43 metabolites significantly differed depending on the accumulation of SUV in tumors. Metabolites involved in the removal of reactive oxygen species (e.g., hypotaurine, glutathione, Met), treatment resistance (UDP-N-acetylglucosamine), and proliferation (e.g., choline, leucine, isoleucine) were increased in the high SUVmax group., Conclusion: FDG accumulation is an important independent prognostic factor reflecting tumor activity associated with metabolic changes in cancer cells., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To assess right heart diastolic energy loss (EL) as a cardiac workload and evaluate its association with major cardiac events (MACE) in adult patients with pulmonary atresia with an intact ventricular septum (PAIVS)., Methods: We retrospectively enrolled and compared 30 consecutive adult patients (18 with PAIVS and 12 with pulmonary stenosis [PS] as controls) who underwent right ventricular (RV) outflow tract reconstruction and 4D flow MRI. EL, conventional parameters on MRI, and the severity of tricuspid regurgitation (TR) on echocardiography were assessed. We also evaluated the association between MACE including arrhythmias, heart failure, surgical intervention, and imaging parameters in adults with PAIVS., Results: Patients with PAIVS were younger, had a higher diastolic EL/cardiac output (CO) ratio, and had a more significant TR than those with PS (controls). However, RV volume, ejection fraction (EF), and pulmonary regurgitation (PR) severity did not differ between the two groups. Higher RV end-diastolic pressure (EDP) and lower cardiac index (CI) correlated with the diastolic EL/CO in patients with PAIVS. Univariate logistic analysis demonstrated that older age and a higher diastolic EL/CO ratio were important factors for MACE in adults with PAIVS (P = 0.048, 0.049)., Conclusion: A higher diastolic EL/CO ratio was associated with a higher RV EDP and lower CI. A high diastolic EL/CO ratio is also associated with MACE in adults with PAIVS. Even in adults with normal RV volume and EF, the right heart EL was elevated, suggesting an excessive right-sided cardiac workload that integrated both afterload and preload beyond the RV size in adult patients with PAIVS.

Staphylococcus epidermidis is a member of the human skin microbiota as a commensal organism but could be an important opportunistic pathogen for immunocompromised individuals. Here, we report the complete genome sequence of three S . epidermidis strains isolated from patients with skin diseases., Competing Interests: The authors declare no conflict of interest.

The optimal structure of synthetic glycopolymers for GM1 mimetics was determined through Bayesian optimization. The interactions of glycopolymers carrying galactose and neuraminic acid units in different compositions with cholera toxin B subunit (CTB) were assessed by an enzyme-linked immunosorbent assay (ELISA). Gaussian process regression, using the ELISA results, predicted the composition of glycopolymers that would exhibit stronger interactions with CTB. Following five cycles of optimization, the glycopolymers carrying 60 mol% galactose and 25 mol% neuraminic acid demonstrated an IC 50 value of 75 μM for CTB, representing the lowest value among the synthesized glycopolymers.

A quantitative understanding of thermodynamic effects of avidity in biomolecular interactions is important. Herein, we synthesized discrete glycooligomers and evaluated their interactions with a model protein using isothermal titration calorimetry. The dimeric glycooligomer exhibited higher binding constants compared to the glycomonomer, attributed to the reduced conformational entropy loss through local presentation of multiple carbohydrate units. Conversely, divalent glycoligands with polyethylene glycol linkers, aiming for multivalent binding, showed enhanced interactions through increased enthalpy. These findings emphasize the importance of distinguishing between the "local avidity" and the "multipoint avidity".

Background: The number of football teams in senior categories has increased. As outdoor sports entail players being exposed to sunlight, playing football may contribute to maintaining vitamin D stores and body mineral density while preventing osteoporosis. This study aimed to determine the bone mineral density and vitamin D levels in middle-aged premenopausal female football players., Methods: Participants were premenopausal females in their 40s. We evaluated bone mineral density of the second to the fourth lumbar vertebrae and femoral neck, serum 25-hydroxy vitamin D (25-OHD) levels, which is an indicator of vitamin D stores, and body composition. In addition, we administered a questionnaire survey on exercise habits and lifestyle. Ninety-two participants were categorised into three groups: the football group (n = 27), volleyball group (n = 40), and non-exercise group (n = 25)., Results: Bone mineral density was higher in the football and volleyball groups than in the non-exercise group (P < 0.01). The volleyball group had a significantly higher bone mineral density of the lumbar spine and femoral neck than the non-exercise group (P < 0.01). The football group had a significantly higher bone mineral density of the femoral neck than the non-exercise group (P < 0.01). Although the football group had played fewer years than the volleyball group (P < 0.01), serum 25-OHD levels were the highest in the football group and were significantly higher than those in the volleyball and non-exercise groups (P < 0.01)., Conclusions: Middle-aged premenopausal football players had higher body vitamin D levels and bone mineral densities than non-active females. These results suggest that playing football may contribute to the prevention of osteoporosis., Trial Registration: UMIN Clinical Trials Registry UMIN000054235. 2024/04/23. Retrospectively registered., (© 2024. The Author(s).)

Objective: Widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in the number of reported cases of immunotherapy-related endocrinopathies. This study aimed to analyze and compare human leukocyte antigen (HLA) signatures associated with ICI-induced type 1 diabetes (ICI-T1D) and isolated adrenocorticotropic hormone deficiency (ICI-IAD) in patients with both conditions., Methods: HLA signatures were examined for their frequencies of occurrence in 22 patients with ICI-T1D without concurrent IAD, including 16 patients from nationwide reports (ICI-T1D group) and 14 patients with ICI-IAD without concurrent T1D (ICI-IAD group). The HLA signatures were also compared for their respective frequencies in 11 patients with ICI-T1D and ICI-IAD, including eight from nationwide reports (ICI-T1D/IAD group)., Results: In the ICI-T1D group, HLA-DRB1*09:01-DQB1*03:03 and DQA1*03:02, which are in linkage disequilibrium with DRB1*09:01-DQB1*03:03 and DRB1*13:02-DQB1*06:04, were susceptible to ICI-T1D, whereas DRB1*15:02-DQB1*06:01 was protective against ICI-T1D. In the ICI-IAD group, DPB1*09:01, C*12:02-B*52:01, and DRB1*15:02-DRB1*06:01, which are in strong linkage disequilibrium, were associated with susceptibility to ICI-IAD. Moreover, DRB1*15:02-DRB1*06:01 was not detected in the ICI-T1D/IAD group., Conclusions: This study revealed specific HLA signatures associated with ICI-T1D and ICI-IAD. Moreover, HLA-DRB1*15:02-DRB1*06:01, an ICI-IAD-susceptible HLA haplotype, coincides with the ICI-T1D-protective HLA haplotype, suggesting that the presence of DRB1*15:02-DRB1*06:01 may protect against the co-occurrence of T1D in patients with ICI-IAD., Competing Interests: Conflict of interest: The authors declare no conflicts of interest associated with this manuscript., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: The accurate age estimation of cadavers is essential for their identification. However, conventional methods fail to yield adequate age estimation especially in elderly cadavers. We developed a deep learning algorithm for age estimation on CT images of the vertebral column and checked its accuracy., Method: For the development of our deep learning algorithm, we included 1,120 CT data of the vertebral column of 140 patients for each of 8 age decades. The deep learning model of regression analysis based on Visual Geometry Group-16 (VGG16) was improved in its estimation accuracy by bagging. To verify its accuracy, we applied our deep learning algorithm to estimate the age of 219 cadavers who had undergone postmortem CT (PMCT). The mean difference and the mean absolute error (MAE), the standard error of the estimate (SEE) between the known- and the estimated age, were calculated. Correlation analysis using the intraclass correlation coefficient (ICC) and Bland-Altman analysis were performed to assess differences between the known- and the estimated age., Results: For the 219 cadavers, the mean difference between the known- and the estimated age was 0.30 years; it was 4.36 years for the MAE, and 5.48 years for the SEE. The ICC (2,1) was 0.96 (95 % confidence interval: 0.95-0.97, p < 0.001). Bland-Altman analysis showed that there were no proportional or fixed errors (p = 0.08 and 0.41)., Conclusions: Our deep learning algorithm for estimating the age of 219 cadavers on CT images of the vertebral column was more accurate than conventional methods and highly useful., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Although low high-density lipoprotein cholesterol (HDL-C) levels are a common metabolic abnormality associated with insulin resistance, their role in cardiovascular risk stratification remains controversial. Recently, we developed a simple, high-throughput, cell-free assay system to evaluate the "cholesterol uptake capacity (CUC)" as a novel concept for HDL functionality. In this study, we assessed the CUC in patients with hypertriglyceridemia and diabetes mellitus., Methods: The CUC was measured using cryopreserved serum samples from 285 patients who underwent coronary angiography or percutaneous coronary intervention between December 2014 and May 2019 at Kobe University Hospital., Results: The CUC was significantly lower in diabetic patients (n = 125) than in nondiabetic patients (93.0 vs 100.7 arbitrary units (A.U.), P = 0.002). Patients with serum triglyceride (TG) levels >150 mg/dL (n = 94) also had a significantly lower CUC (91.8 vs 100.0 A.U., P = 0.004). Furthermore, the CUC showed a significant inverse correlation with TG, hemoglobin A1c (Hb A1c), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Finally, the HDL-C/Apolipoprotein A1 (ApoA1) ratio, calculated as a surrogate index of HDL particle size, was significantly positively correlated with the CUC (r2 = 0.49, P < 0.001), but inversely correlated with TG levels (r2 = -0.30, P < 0.001)., Conclusions: The CUC decreased in patients with hypertriglyceridemia and diabetes mellitus, and HDL particle size was a factor defining the CUC and inversely correlated with TG levels, suggesting that impaired CUC in insulin-resistant states was partially due to the shift in HDL towards smaller particles. These findings provide a better understanding of the mechanisms underlying impaired HDL functionality., (Published by Oxford University Press on behalf of Association for Diagnostics & Laboratory Medicine 2024.)

Objectives: Disaster evacuation increases the risk of becoming overweight or obese owing to lifestyle changes and psychosocial factors. This study evaluated the effect of evacuation on becoming overweight during a 7-year follow-up among residents of Fukushima Prefecture during the Great East Japan Earthquake., Study Design: This was a prospective cohort study., Methods: We analysed data collected from 18,977 non-overweight Japanese participants who completed the 'Comprehensive Health Checkup Program' and 'Mental Health and Lifestyle Survey', as part of the Fukushima Health Management Survey, between July 2011 and November 2012. An evacuation was defined as the moving out of residents of municipalities designated as an evacuation zone by the government or having a self-reported experience of moving into shelters or temporary housing. Follow-up examinations were conducted in March 2018 to identify patients who became overweight. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using a Cox proportional hazards regression model., Results: Among 15,875 participants (6091 men and 9784 women; mean age 63.0 ± 11.1 years) who received follow-up examination (mean follow-up, 4.29 years), 2042 (856 men and 1186 women) became overweight. Age-, baseline body mass index-, lifestyle-, and psychosocial status-adjusted HRs (95% CIs) for becoming overweight after evacuation were 1.44 (1.24-1.66) for men and 1.66 (1.47-1.89) for women., Conclusion: Evacuation was associated with the risk of becoming overweight 7 years after the disaster. Thus, maintaining physical activity, healthy diet, and sleep quality and removing barriers to healthy behaviour caused by disasters, including anxiety concerning radiation, may prevent this health risk among evacuees., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: A chronic expanding hematoma is an uncommon entity described as an organized blood collection that increases in size after the initial hemorrhagic event without histological neoplastic features. The standard treatment is complete resection. To our knowledge, this is the first report of a chronic expanding hematoma mimicking a pancreatic cystic tumor that has been successfully resected utilizing a laparoscopic approach., Case Presentation: We report the case of a 32-year-old man with a 10-cm chronic expanding hematoma that was preoperatively diagnosed as a cystic pancreatic tumor. Dynamic computed tomography revealed a cyst at the inferior part of the uncinate process of the pancreas without contrast enhancement. His blood biochemical data were within normal limits. The operation initially utilized a laparoscopic approach; however, the procedure was converted to hand-assisted laparoscopic surgery due to capsule adherence to surrounding organs and finally, enucleation of the tumor was performed. Pathological findings revealed a chronic expanding hematoma in the retroperitoneal space., Conclusion: Chronic expanding hematoma in the retroperitoneal space is so rare and sometimes adheres to the surrounding tissue. It is difficult to distinguish hematoma attaching pancreas and pancreatic cyst preoperatively. In rare cases such as this, hand-assisted laparoscopic surgery is a feasible, less invasive procedure for facilitating complete resection and preventing recurrence., (© 2024. The Author(s).)

Introduction: Methadone is used to treat intractable cancer pain when other opioid analgesics are ineffective. Methadone tablets may be difficult to administer in cases of gastrointestinal passage obstruction. However, changing the route of methadone tablet administration is possible. Case Description: The patient, diagnosed with esophagogastric junction cancer with multiple metastases, continued to receive methadone tablets even after not being longer able to take oral medication. Method: Methadone tablets were administered using a simple suspension method via gastrostomy. We measured the respiratory rate during sleep daily. We also measured weekly QTc values using a 12-lead electrocardiogram and methadone blood concentration periodically. No side effects were observed. Conclusion: Using a simple suspension method to administer methadone is a safe pain management method when accompanied by careful monitoring. To date, no study has examined the tube administration safety of methadone tablets. Thus, this case report is of important clinical significance.

Background: Ganciclovir and its prodrug, valganciclovir, are first-line agents for cytomegalovirus infection prophylaxis after lung transplantation. Although valganciclovir prophylaxis is known to result in severe leukopenia as an adverse effect, dosage adjustment based on therapeutic drug monitoring (TDM) of ganciclovir concentration is not generally implemented in clinical practice., Case Presentation: In this report, we describe the case of a female in her fifties after lung transplantation who successfully maintained valganciclovir prophylaxis under TDM with a minimal occurrence of severe leukopenia. Valganciclovir administration was initiated at a conventional dose of 450 mg/day on postoperative day 43 but was reduced to 450 mg/2 days on postoperative day 69 because of a decrease in white blood cell count and an increase in trough ganciclovir concentration. Subsequently, the valganciclovir dose adjustment was switched from label-indicated renal function-guided dosing to TDM-based dosing, targeting a trough level of 300-800 ng/mL. This target range was determined through deliberations with infectious disease specialists and pharmacists based on previously reported data. The TDM-based dose adjustment successfully prevented cytomegalovirus reactivation without causing significant adverse effects. Valganciclovir prophylaxis was completed on postoperative day 256, and the patient was transferred to another hospital for rehabilitation., Conclusions: The findings of the present case suggest that TDM-based dosing could be helpful for clinicians in optimizing the prophylactic administration of valganciclovir in patients undergoing lung transplantation., (© 2024. The Author(s).)

The crystallinity, solubility, and physical properties of polyhedral oligomeric silsesquioxane (POSS) compounds are highly dependent on their organic substituents. We previously synthesized a series of isobutyl-substituted star-shaped POSS derivatives with aliphatic chain linkers of different length. In this study, we prepared C3- and C6-linked phenyl-substituted star-shaped POSS derivatives ( 3 Ph-C3 and 3 Ph-C6 ) by the hydrosilylation of heptaphenylallyl- and hexenyl-POSS ( 1a and 1b M 8 -silsesquioxane (Q 8 M 8 H ) ( 2 ), respectively, and their properties were compared with those of the corresponding isobutyl-substituted derivatives ( 5 iBu-C3 and 5 iBu-C6 ). Although 3 Ph-C6 was only soluble in chloroform and insoluble in tetrahydrofuran (THF) and toluene, 3 Ph-C3 was soluble even in THF and toluene, suggesting that the shorter linkers of the derivative afford a wider range of solvents for dissolution. Differential scanning calorimetry analysis showed that 3 Ph-C3 exhibited a baseline shift at 190 °C and an endothermic peak at 316 °C. However, no clear baseline shift was observed for 3 Ph-C6 . Thermogravimetric analysis showed that the shorter linker in the phenyl-substituted star-shaped POSS derivative significantly increased the decomposition temperature compared with the longer linker. The annealed cast film of 3 Ph-C3 at 340 °C above its melting temperature formed a transparent film even after cooling to room temperature. However, an opaque whitish film was formed in the case of 3 Ph-C6 . Poly(methyl methacrylate) (PMMA) films containing 2 wt % 3 Ph-C3 and 3 Ph-C6 were prepared by casting their chloroform solutions onto glass substrates overnight at room temperature. The static water contact angle measurements and XPS analysis for the castings film containing 3 Ph-C3 and 3 Ph-C6 suggested that degree of the segregation amount of 3 Ph-C3 was larger than that of 3 Ph-C6 . The shorter linker length in the phenyl-substituted star-shaped POSS derivative, 3 Ph-C3 , with its greater predicted solubility in PMMA, exhibited entropy-driven surface segregation.