Search

Background: The uncertainty including accuracy and precision is the most vital factor that determines the overall quality of quantitative analysis. The uncertainty has been, however, evaluated relatively within the same analytical technique. Given this background, the present study evaluates the uncertainty on quantitative elemental analysis with a quasi-absolute approach. The objectives of this study are (1) to investigate the analytical uncertainty of prompt gamma-ray analysis (PGA), a chemical interference-free method in principle, on the quantitative analysis of boron and (2) to evaluate the applicability of inductively coupled plasma optical emission spectrometry (ICP-OES), a common technique for quantitative elemental analysis including boron., Results: PGA provided analytical quantity that is equivalent to the true quantity. The quantity values determined for a series of boron-containing samples are all well above the detection limit of the PGA system, the quantity resolution of which is also much smaller than the minimum difference in quantity among the samples. These facts confirm that the evaluation of analytical uncertainty with the present PGA system is statistically meaningful. The analytical uncertainty in both methods was adequately evaluated by comparing the results from PGA and ICP-OES for a series of boron-containing materials with different physical/chemical properties (i.e. CrB 2 , B 4 C, and solidified products of stainless steel-B 4 C melt) and the major sources of uncertainty in both methods are specified. The conditions for sample preparation/pretreatment were optimized to lower the uncertainty., Significance and Novelty: This study proposes a new concept to perform the quasi-absolute evaluation of analytical uncertainty by employing a chemical interference-free technique. The proposed concept is not limited to the combination of PGA and ICP-OES as demonstrated in this study, but it is applicable to any combination of any analytical methods for any element. Hence, the concept demonstrated in this study could be beneficial to a wide range of analytical chemistry., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Takehiro Sumita reports financial support was provided by Japan Society for the Promotion of Science. Takehiro Sumita reports financial support was provided by Iketani Science and Technology Foundation. If there are other authors, they 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: In recent years, dental implant treatment has become an option for prosthetic treatment for missing teeth and is often performed in older patients. However, the complex oral functional decline in old age presents challenges in terms of frailty prevention, making oral function management after prosthetic treatment crucial. Nonetheless, the actual status of oral function in older patients seeking dental implant treatment remains unclear. In this study, we aimed to assess the oral function status of older patients seeking dental implant treatment., Methods: Among patients receiving prosthetic treatment for missing teeth, 227 older patients (111 in the pre-dental implant group and 116 in the pre-bridge/denture group) who underwent a thorough examination of their oral function were included in this study. Age, sex, comorbidities, smoking status, number of functional teeth, and occlusal support status were obtained from the medical records. Statistical analyses were performed using the t-test, chi-square test, and logistic regression (p < 0.05)., Results: Compared with the pre-bridge/denture group, the pre-dental implant group had significantly better oral hygiene, occlusal force, tongue-lip motor function, tongue pressure, masticatory function, and swallowing function and a significantly lower prevalence of oral hypofunction. Older age and decreased occlusal support were associated with the diagnosis of oral hypofunction, even after adjusting for confounding factors including prosthetic treatment., Conclusions: Although older patients seeking dental implant treatment have a higher oral function than those seeking general prosthetic treatment, older age and a lower number of occlusal supports suggest that appropriate oral function management is needed., (© 2024. The Author(s).)

Objective: To evaluate comorbidities in Japanese testicular cancer (TC) survivors in a multi-institutional, cross-sectional study., Methods: This study enrolled TC survivors who visited any of the eight high-volume institutions in Japan from 2018 to 2019. After obtaining informed consent, participants answered questionnaires about their comorbidities. We analyzed the impact of treatment on comorbidities rate in TC survivors., Results: A total of 509 TC survivors responded to the comorbidity questionnaires. Median age at the time of response was 43 years (IQR 35-51 years) and median follow-up period after treatment was 5.1 years (IQR 2.1-9.2 years). TC survivors were divided according to the number of cycles of chemotherapy into the following groups: None (n = 153); 1-2 cycles (n = 34); 3-4 cycles (n = 234); or ≥5 cycles (n = 88). The prevalence of kidney disease increased significantly with increasing number of cycles of chemotherapy (p < 0.05). The relative risk of cardiovascular disease in the groups with three or more cycles was 2.6 compared to the group without chemotherapy., Conclusion: The present study showed that the prevalence of kidney disease in TC survivors was increased with increasing number of cycles of chemotherapy., (© 2024 The Japanese Urological Association.)

Linalool is anticipated to have significant ecological roles. In this study, linalyl 6-O-α-arabinopyranosyl-β-D-glucopyranoside (linalyl β-vicianoside: LinVic) was synthesized, and a linalool diglycoside purified from soybean leaves was identified as LinVic by using liquid chromatography-mass spectrometry. High levels of LinVic were detected in leaves and sepals during soybean plant growth. The LinVic content did not significantly increase following methyl jasmonate treatment of the leaves, indicating that its synthesis is independent of the jasmonic acid signaling pathway. In addition to LinVic, soybean also contains 1-octen-3-yl primeveroside. We treated soybean leaves with vaporized linalool and 1-octen-3-ol to determine whether the glycosylation system discriminates between these two volatile alcohols. Linalool treatment resulted in the accumulation of LinVic, while 1-octen-3-ol treatment caused little change in the amount of 1-octen-3-yl primeveroside, suggesting discrimination between these compounds. Linalool-treated soybean leaves exhibited increased resistance against common cutworms, indicating that LinVic may contribute to herbivore resistance., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: Significant sac shrinkage after endovascular aortic aneurysm repair (EVAR) is generally considered a positive outcome indicative of durable clinical success. However, its impact on endograft configuration is rarely addressed. Sac remodeling and volume loss due to shrinkage can potentially cause deformation of endograft components, resulting in limb angulation and compression. We investigated the hypothesis that significant sac shrinkage could affect endograft tortuosity at 5 years post-EVAR., Methods: We retrospectively reviewed patients who underwent elective EVAR for infrarenal abdominal aortic aneurysm between June 2007 and December 2018. Patients with early postoperative and 5-year follow-up computed tomography images were included. Patients treated with modular bifurcated endografts (Zenith, Endurant, Excluder, and Incraft) were analyzed. The "shrinkage" group comprised patients with >10 mm diameter reduction, while the "stable" group had ± 5 mm diameter change at 5 years. Tortuosity index (TI) was calculated as the ratio of centerline distance to straight-line distance between proximal and distal endograft edges. The association between sac shrinkage and ≥5% increase of TI (≥5%ΔTI) was analyzed for both ipsilateral and contralateral sides., Results: Of 136 patients enrolled, 80 were in the shrinkage group and 56 in the stable group. On the ipsilateral side, ≥5%ΔTI was observed in 24 cases (17.6%). The patients with ipsilateral ≥5%ΔTI had significantly shorter median neck lengths (22 mm vs. 30 mm, P = 0.030). Sac shrinkage ≥15 mm was negatively associated with ≥5%ΔTI compared to stable sac (P = 0.027). Logistic regression showing sac shrinkage ≥15 mm had a significant negative correlation with ≥5%ΔTI (P = 0.025, hazard ratio [95% confidence interval]: 0.218 [0.057-0.824]). On the contralateral side, ≥5%ΔTI (19 cases, 14.0%) was associated with shorter neck length but not with sac shrinkage. In the shrinkage group, cross-leg positioning resulted in a significant increase in ipsilateral TI at 5 years compared to straight positioning (median ΔTI: 1.8% vs. 0.0%, P = 0.013). No reinterventions for leg-related events were necessary during the 5-year follow-up period., Conclusions: Contrary to our initial hypothesis, significant sac shrinkage does not adversely affect endograft configuration and may help stabilize tortuosity on the ipsilateral side. However, in patients with crossed-leg configuration, continued vigilant observation may be warranted even after achieving sac shrinkage, as it could exacerbate tortuosity. Shorter neck length was associated with increased tortuosity on both sides. Further research is needed to confirm these findings and consider potential confounding factors, including the impact of different endograft designs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Human activities introduce new environmental cues to wild organisms, leading to maladaptive behavioral and life history decisions known as the "evolutionary trap." This trap is thought to be a major conservation concern for free-living organisms. However, it has never been studied in endosymbionts, one of the most successful and diverse life forms on Earth. Here, we examine this trap in the extended phenotype of a parasite that exploits the visual system of hosts to alter host behavior for its benefit. Arboreal mantids infected by nematomorph parasites are drawn to horizontally polarized light, thereby inducing them to enter the water. In this study, we found that the degree of linear polarization (DOP) of reflected light served as a reliable environmental cue for identifying perennial waters, where nematomorphs can survive in their aquatic life stage without drying out. Infected mantids exhibit attraction to horizontally polarized light with higher DOP in behavioral assays and jumped into pools reflecting light with higher DOP in field experiments. The asphalt road reflected horizontally polarized light closely resembling the polarization levels observed in perennial waters, likely leading to a higher prevalence of mantids on asphalt roads compared with those found in natural arboreal habitats. In a field experiment, we observed infected mantids walking on asphalt roads more often than on cement roads. These findings imply that evolutionary traps can endanger endosymbionts beyond their hosts that directly perceive environmental cues., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Objective: This study aims to assess the surgical outcome of borderline hypoplastic left ventricle before and after the induction of the left ventricle rehabilitation strategy., Methods: A retrospective review investigated patients with borderline hypoplastic left ventricle who underwent surgical intervention between 2012 and 2022. The patient cohort was stratified into two groups based on the initiation of left ventricle rehabilitation: an early-era group (E group, 2012-2017) and a late-era group (L group, 2018-2022). Left ventricle rehabilitation was defined as palliation combined with other procedures aimed at promoting left ventricular growth such as restriction of atrial septal defect, relief of inflow/outflow obstructive lesions, and resection of endocardial fibroelastosis., Results: A total of 58 patients were included. Primary diagnosis included 12 hypoplastic left heart syndromes, 11 critical aortic valve stenosis, and others. A total of 9 patients underwent left ventricle rehabilitation, 8 of whom underwent restriction of atrial septal defect. As for clinical outcomes, 9 of 23 patients achieved biventricular repair in the E group, whereas in the L group, 27 of 35 patients achieved biventricular repair (39% vs. 77%, p = 0.004). Mortality did not differ statistically between the two groups (log-rank test p = 0.182). As for the changes after left ventricle rehabilitation, left ventricular growth was observed in 8 of 9 patients. The left ventricular end-diastolic volume index (from 11.4 to 30.1 ml/m 2 , p = 0.017) and left ventricular apex-to-right ventricular apex ratio (from 86 to 106 %, p = 0.014) significantly increased after left ventricle rehabilitation., Conclusions: The introduction of the left ventricle rehabilitation strategy resulted in an increased proportion of patients achieving biventricular repair without a concomitant increase in mortality. Left ventricle rehabilitation was associated with enhanced left ventricular growth and the formation of a well-defined left ventricle apex. Our study underscores the significance of left ventricle rehabilitation strategies facilitating successful biventricular repair. The data suggest establishing restrictive atrial communication may be a key factor in promoting left ventricular growth.

Objective: To clarify the association of the aortopulmonary collaterals (APCs)/venovenous collateral (VVCs) in patients with plastic bronchitis (PB) after the Fontan procedure., Methods: All patients who underwent total cavopulmonary connection from 1994 to 2022 were reviewed. APCs/VVCs were detected using angiography. The impact of APC/VVCs, as well as other variables on the onset of plastic bronchitis, was evaluated., Results: A total of 635 patients were included. Plastic bronchitis was observed in 15 (2.4%) patients, and the median duration between total cavopulmonary connection and the onset of plastic bronchitis was 1.1 years. Freedom from PB at 5 and 10 years was 97.5% and 96.5%, respectively. As for the association of PB and APCs/VVCs, patients with PB had an increased incidence of post-total cavopulmonary connection APCs (60% vs 14%, P < .001) and VVCs (53% vs 14%, P < .001). Freedom from PB was the lowest in the patients who were associated with both APCs and VVCs after total cavopulmonary connection. APCs after total cavopulmonary connection (P = .002; hazard ratio, 5.729), VVCs after total cavopulmonary connection (P = .016; hazard ratio, 3.527), and chylothorax (P = .019; hazard ratio, 3.662) were identified as independently associated factors with the onset of PB., Conclusions: The occurrence of post-Fontan APCs and VVCs was significantly associated with the development of PB. Treatment or mitigation of collaterals may represent an opportunity to prevent the development of PB, a remaining source of post-Fontan excess morbidity and mortality., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine how the treatment decision-making process and posttreatment health-related quality of life (HRQOL) are related to regret about treatment choice for prostate cancer patients in Japan., Methods: We invited a total of 614 patients who were treated with radiation therapy (RT), radical prostatectomy (RP), or active surveillance/watchful waiting (AS/WW) from April 2007 to March 2021. Posttreatment regret was evaluated by the Decision Regret Scale. HRQOL was evaluated by the Expanded Prostate Cancer Index Composite and the 12-item Short Form Survey. The decision-making process was assessed by patient evaluation of the decision-making process. We compared the decision regret scale scores across treatment types, HRQOL, and decision-making processes., Results: Data from 371 patients were analyzed (RT: 202, RP: 149, AS/WW: 20). The median length of time since treatment was 64 (IQR: 43-93) months. The decision regret scale scores were not significantly different among the treatment groups but were significantly greater (strong regret) in patients with poor urinary summary scores, bowel summary scores, and hormonal summary scores. The decision regret scale scores were significantly lower (less regret) for patients who reported being adequately informed at the time of the treatment decision and who had adequately communicated their questions and concerns to physicians than for patients who reported less adequate communication. This result was also observed among patients who reported low HRQOL scores., Conclusions: These findings underline the important influence of posttreatment HRQOL and decision-making as an interactive process between physicians and their patients on posttreatment regret in prostate cancer patients., (© 2024 The Japanese Urological Association.)

An 85-year-old man with a history of 2 open-heart surgeries (for aortic regurgitation and infective endocarditis [IE]) and pacemaker implantation for bradycardic atrial fibrillation presented with a fever. Transesophageal echocardiography revealed a pacemaker lead vegetation. Computed tomography showed a retrosternal abscess. He was diagnosed with acute heart failure and IE. Given the high surgical risk due to his age, acute heart failure, and surgical history, we decided against cardiac surgery. After lead extraction, a leadless pacemaker was inserted, and antimicrobial therapy was administered. The patient was discharged on day 48, highlighting a strategy for managing complex cardiac device-related IE.

Objective: We aimed to compare the pulmonary artery (PA) growth between infants with univentricular hearts who underwent a ductus stenting (DS) and those who received a systemic to pulmonary shunt (SPS) as an initial palliation., Methods: All infants with ductal-dependent pulmonary blood flow who underwent initial palliation with either a DS or SPS between 2009 and 2022 in our institution were reviewed. PA development was compared between the groups using the PA index and the symmetry index., Results: A total of 130 patients were evaluated including 49 patients after DS and 81 after SPS. The most frequent primary diagnosis was tricuspid atresia in 27, followed by pulmonary atresia with intact ventricular septum in 19. At stage II palliation, PA index (P = .926), right PA index (P = .692), left PA index (P = .297), and the symmetry index (P = .650) were similar between the groups. At stage III Fontan completion, PA index (P = .115), right PA index (P = .868), and the symmetry index (P = .144) were similar between the groups. However, left PA index (60 vs 74 mm 2 /m 2 ; P = .015) was lower, and the incidence of venovenous collaterals (24.2% vs 7.8%; P = .036) was higher in the DS group compared with the SPS group. Freedom from PA interventions between stage II and III palliation was lower in the DS group compared with the SPS group (P = .009)., Conclusions: In infants with univentricular heart after DS, freedom from PA interventions after stage II was lower and the left PA index was smaller, compared with those after SPS. Long-term outcomes after the Fontan procedure should be addressed in patients after DS., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Advanced (Stage IV) prostate and renal cancer have poor prognosis, and several therapies have been developed, but many are very costly. This study investigated drug regimens used in patients with untreated Stage IV prostate cancer and renal cell carcinoma and calculated the monthly cost of each., Methods: We surveyed first-line drugs administered to patients with untreated Stage IV prostate cancer and renal cancer at Japan Clinical Oncology Group affiliated centers from April 2022 to March 2023. Drug costs were calculated according to drug prices in September 2023. Individual drug costs were calculated or converted to 28-day costs., Results: A total of 700 patients with untreated Stage IV prostate cancer were surveyed. Androgen deprivation therapy + androgen receptor signaling inhibitor was the most common regimen (56%). The cost of androgen deprivation therapy + androgen receptor signaling inhibitor was 10.6-30.8-fold compared with conventional treatments. A total of 137 patients with Stage IV renal cancer were surveyed. Among them, 91% of patients received immune-oncology drug-based regimen. All patients received treatments with a monthly cost of ≥500 000 Japanese yen, and 80.4% of patients received treatments with a monthly cost of ≥1 million Japanese yen, of combination treatments. The cost of immune-oncology drug-based regimen was 1.2-3.1-fold that of TKI alone., Conclusion: To the best of our knowledge, this is the first report of a survey of first-line drug therapy in untreated Stage IV prostate cancer and renal cell carcinoma stratified by age and treatment costs. Our results show that most Japanese patients received state-of-the-art, effective treatments with high financial burden., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Our aim was to develop practical training for laparoscopic surgery using Thielembalmed cadavers. Furthermore, in order to verbalize experts' motion characteristics and provide objective feedback to trainees, we initiated motion capture analyses of multiple surgical instruments simultaneously during the cadaveric trainings. In the present study, we report our preliminary results., Methods: Participants voluntarily joined the present cadaveric simulation trainings, and performed laparoscopic radical nephrectomy. After the trainings, scores for tissue similarity (face validity) and impression of educational merit (content validity) were collected from participants based on a 5-point Likert scale (tissue similarity: 5: very similar, 3: average, 1: very different; educational merit: 5: very high, 3: average, 1: very low). In addition, after the additional IRB approval, we started motion capture (Mocap) analyses of 6 surgical instruments (scissors, vessel sealing system, grasping forceps, clip applier, right-angled forceps, and suction), using an infrared trinocular camera (120-Hz location record). Mocap-metrics were compared according to the previous surgical experiences (experts: ≧50 laparoscopic surgeries, intermediates: 10-49, novices: 0-9), using the Kruskal-Wallis test., Results: A total of 9 experts, 19 intermediates, and 15 novices participated in the present study. In terms of face validity, the mean scores were higher than 3, other than for the Vena cava(mean score of 2.89). Participants agreed with the training value (usefulness for future skill improvement: mean score of 4.57). In terms of Mocap analysis, faster speed-related metrics (e.g., velocity, the distribution of tip velocity, acceleration, and jerk) in the scissors and vessel sealing system, a shorter path length of grasping forceps, and fewer dimensionless squared jerks, which indicated more purposeful motion of 4 surgical instruments (vessel sealing system, grasping forceps, clip applier and suction), were observed in the more experienced group., Conclusions: The Thiel-embalmed cadaver provides an excellent training opportunity for complex laparoscopic procedures with participants' high level of satisfaction, and may become a promising tool for a better objective understanding of surgical dexterity. In order to enrich formative feedback to trainees, we are now proceeding with Mocap analysis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims/introduction: History of coronary artery disease (CAD), cerebrovascular disease (CeVD), type 2 diabetes and their combined effect on cardiovascular disease are essential for cardiovascular risk management. We investigated the association of prior CAD, prior CeVD, type 2 diabetes and their combination with the risk of cardiovascular disease., Materials and Methods: This is a historical cohort study including 342,033 participants (aged 18-72 years) followed up for ≥5 years between 2008 and 2016. Participants were classified into eight groups (with or without prior CAD, prior CeVD and type 2 diabetes). Type 2 Diabetes was defined by fasting plasma glucose and glycated hemoglobin levels, and antidiabetic drug prescription. Prior and subsequent CAD and CeVD were identified according to claims using International Classification of Diseases 10th Revision codes, medical procedures and questionnaires. Cox regression models were used to evaluate the risk of cardiovascular events., Results: The median follow-up period was 6.4 years. The incidence of composite cardiovascular events of CAD and CeVD in the CAD-/CeVD-, CAD+/CeVD-, CAD-/CeVD+ and CAD+/CeVD+ groups were 1.92 and 6.94, 25.14 and 31.98 per 1,000 person-years in non-diabetes participants, and 8.66, 18.04, 39.98 and 60.72 in type 2 diabetes patients, respectively. Hazard ratios of cardiovascular events compared with CAD-/CeVD-/non-diabetes were 1.66 (95% confidence interval 1.55-1.78) in CAD-/CeVD-/type 2 diabetes and 1.84 (1.56-2.18) in CAD+/CeVD-/non-diabetes. CeVD+ was linked to a 4-7-fold increase in the risk of cardiovascular events regardless of CAD+ or type 2 diabetes., Conclusions: Type 2 diabetes increased the risk of cardiovascular disease as high as a history of CAD, whereas prior CeVD alone increased the risk of future CeVD without additional effects by type 2 diabetes., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: We have left antegrade pulmonary blood flow (APBF) at bidirectional cavopulmonary shunt (BCPS) only for high-risk patients. This study evaluates the indication and the outcomes of patients with APBF, compared to those without APBF., Methods: Patients with APBF after BCPS were identified among patients who underwent BCPS between 1997 and 2022. Outcomes of patients with and without APBF after BCPS were compared., Results: APBF was open in 38 (8.2%) of 461 patients. Median age (7.7 versus 6.3 months, p = 0.55) and weight (5.6 versus 6.1 kg, p = 0.75) at BCPS were similar in both groups. The most frequent indication for APBF was high pulmonary artery pressure (PAP) in 14 patients, followed by hypoxaemia in 10, and hypoplastic left pulmonary artery in 8. The source of APBF was the pulmonary trunk in 10 patients and the aortopulmonary shunt in 28. Median hospital stay after BCPS was longer (22 versus 14 days, p = 0.018) and hospital mortality was higher (10.5 versus 2.1%, p = 0.003) in patients with APBF compared to those without APBF. However, 448 hospital survivors showed similar survival after discharge following BCPS (p = 0.224). Survival after total cavopulmonary connection (TCPC) was similar between the groups (p = 0.753), although patients with APBF were older at TCPC compared to those without (3.9 versus 2.2 years, p = 0.010)., Conclusion: APBF was left in 8% following BCPS in high-risk patients, mainly due to preoperative high PAP. Hospital survivors after BCPS demonstrated comparable survival in patients with and without APBF. Adding APBF at BCPS might be a useful option for high-risk patients.

Background: Undetectable circulating tumor DNA (ctDNA) is an obstacle to performing comprehensive genomic profiling in daily practice to identify genomic alterations. We investigated the associations between clinicopathological factors and undetectable ctDNA using a commercially available comprehensive genomic profiling assay in metastatic prostate cancer., Patients and Methods: Patients treated with systemic treatment for metastatic prostate cancer were included. ctDNA was analyzed by FoundationOne ® Liquid CDx at enrollment. The associations between clinicopathological characteristics and ctDNA detection were analyzed., Results: The number of bone metastasis was associated with ctDNA detection (odds ratio [95% confidence interval], 13.6 [1.71-108], P = 0.014). An algorithm predicting ctDNA detection using clinicopathological parameters was created. If ≥ 4 bone metastases were observed, ctDNA detection was estimated to be 98.9%. Among the patients with < 4 bone metastases, if two or three features among ISUP grade group 5, PSA level ≥ 10 ng/ml, and castration resistance were present, the ctDNA detection rate was 96.7% while the ctDNA detection rate was 86.3% if no or only one feature was present., Conclusions: An algorithm created in this study is helpful in determining when to undertake comprehensive genomic profiling assay using blood., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess the effectiveness of pre- and postoperative supervised pelvic floor muscle training (PFMT) on the recovery of continence and pelvic floor muscle (PFM) function after robot-assisted laparoscopic radical prostatectomy (RARP)., Patients and Methods: We carried out a single-blind randomised controlled trial involving 54 male patients scheduled to undergo RARP. The intervention group started supervised PFMT 2 months before RARP and continued for 12 months after surgery with a physiotherapist. The control group was given verbal instructions, a brochure about PFMT, and lifestyle advice. The primary outcome was 24-h pad weight (g) at 3 months after RARP. The secondary outcomes were continence status (assessed by pad use), PFM function, and the Expanded Prostate Cancer Index Composite (EPIC) score., Results: Patients who participated in supervised PFMT showed significantly improved postoperative urinary incontinence (UI) compared with the control group (5.0 [0.0-908.0] g vs 21.0 [0.0-750.0] g; effect size: 0.34, P = 0.022) at 3 months after RARP based on 24-h pad weight. A significant improvement was seen in the intervention compared with the control group (65.2% continence [no pad use] vs 31.6% continence, respectively) at 12 months after surgery (effect size: 0.34, P = 0.030). Peak pressure during a maximum voluntary contraction was higher in the intervention group immediately after catheter removal and at 6 months, and a longer duration of sustained contraction was found in the intervention group compared with the control group. We were unable to demonstrate a difference between groups in EPIC scores., Conclusion: Supervised PFMT can improve postoperative UI and PFM function after RARP. Further studies are needed to confirm whether intra-anal pressure reflects PFM function and affects continence status in UI in men who have undergone RARP., (© 2024 BJU International.)

Objective: To evaluate the prevalence of veno-venous collaterals (VVCs) after total cavopulmonary connection (TCPC) and analyze their impact on outcomes., Methods: Patients undergoing TCPC between 1994 and 2022 were evaluated. VVCs were identified using angiograms of cardiac catheterizations and their impact on outcomes was analyzed., Results: A total of 635 patients were included. Median age at TCPC was 2.3 (interquartile ranges (IQR): 1.8-3.3) years. The most frequent diagnosis was hypoplastic left heart syndrome in 173 (27.2%) patients. Prior bidirectional cavopulmonary shunt was performed in 586 (92.3%) patients at a median age of 5.3 (3.6-9.9) months. VVCs were found in 94 (14.8%) patients at a median of 2.8 (0.1-11.8) years postoperatively. The prevalence of VVCs was similar between the dominant right and left ventricle (14.7 vs. 14.9%, p = 0.967). Mean pulmonary artery pressure (16.2 vs. 16.0 mmHg, p = 0.902), left atrial pressure (5.5 vs. 5.7 mmHg, p = 0.480), transpulmonary gradient (4.0 vs. 3.8 mmHg, p = 0.554) and oxygen saturation (81.4 vs. 82.6%, p = 0.103) before TCPC were similar between patients with and without VVCs. The development of VVCs did not affect survival after TCPC (p = 0.161). Nevertheless, VVCs were a risk for the development of plastic bronchitis (PB, p < 0.001). Interventional closure of VVCs was performed in 60 (9.4%) patients at a median of 8.9 (0.6-15.1) years after TCPC, and improvement of oxygen saturation was observed in 66% of the patients., Conclusions: The prevalence of VVCs after TCPC was 15%. VVCs had no impact on survival following TCPC but were associated with a high prevalence of PB., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, or publication of this article., (Copyright © 2023. Published by Elsevier B.V.)

A 67-year-old woman with severe aortic stenosis (AS) was transferred to our hospital for large B-cell lymphoma treatment. Because of her high risk of anthracycline-induced cardiotoxicity due to severe AS and low performance status, the patient was initially treated with doxorubicin-free chemotherapy. However, doxorubicin was considered necessary to achieve complete remission. After multidisciplinary team discussions, transcatheter aortic valve replacement (TAVR) was performed without complications. Nine days after TAVR, the patient received the first cycle of anthracycline-containing chemotherapy (R-CHOP). Currently, 12 months after completing 4 cycles of R-CHOP, the patient remains in complete remission without having developed cardiotoxicity.

Background: To assess the impact of low birth weight on early and late outcomes after staged palliation for single ventricle., Methods: Patients after stage 1 palliation for single ventricle in our institution were retrospectively included and divided into two weight groups: 2.5 kg or less (low birth weight) and more than 2.5 kg. The impact of low birth weight on mortality and on the progression to further palliation stages (bidirectional Glenn, stage 2, and total cavopulmonary connection, stage 3) was assessed., Results: A total of 452 patients were included. Patients with low birth weight (n = 37, 8 %) had more frequently associated prematurity and extracardiac anomalies. Early and inter-stage mortality after stage 1 was higher in patients with low birth weight, so that less of these patients reached the next palliation stage (57 % vs. 77 %, p = 0.01, and 38 % vs. 56 %, p = 0.05, for stage 2 and stage 3, respectively). After 5 years, overall survival was inferior in patients with low birth weight (48 % vs. 73 %, p < 0.001). Survival conditioned by stage 2 palliation was inferior in patients with low birth weight compared to the reference group (76 % vs. 89 % after 5 years, p = 0.04). Low birth weight was a risk factor for death in most patients' subgroups, inclusive those with restricted pulmonary blood flow after a systemic-to-pulmonary shunt procedure., Conclusions: During staged palliation of single-ventricle physiology, low birth weight has a detrimental impact on survival extending to beyond stage 2. This study calls for increased vigilance of these patients beyond the first interstage., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Oligonucleotide therapeutics, particularly antisense oligonucleotides (ASOs), have emerged as promising candidates in drug discovery. However, their effective delivery to the target tissues and cells remains a challenge, necessitating the development of suitable drug delivery technologies for ASOs to enable their practical application. In this study, we synthesized a library of chemically modified dipeptide-ASO conjugates using a recent synthetic method based on the Ugi reaction. We then conducted in vitro screening of this library using luciferase-expressing cell lines to identify ligands capable of enhancing ASO activity. Our findings suggest that N-(4-nitrophenoxycarbonyl)glycine may interact with the thiophosphate moiety of the phosphorothioate-modification in ASO. Through our screening efforts, we identified two ligands that modestly reduced luciferase luminescence in a cell type-selective manner. Furthermore, quantification of luciferase mRNA levels revealed that one of these promising dipeptide-ASO conjugates markedly suppressed luciferase RNA levels through its antisense effect in prostate-derived DU-145 cells compared to the ASOs without ligand modification., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The heart comprises many types of cells such as cardiomyocytes, endothelial cells (ECs), fibroblasts, smooth muscle cells, pericytes, and blood cells. Every cell type responds to various stressors (eg, hemodynamic overload and ischemia) and changes its properties and interrelationships among cells. To date, heart failure research has focused mainly on cardiomyocytes; however, other types of cells and their cell-to-cell interactions might also be important in the pathogenesis of heart failure., Methods: Pressure overload was imposed on mice by transverse aortic constriction and the vascular structure of the heart was examined using a tissue transparency technique. Functional and molecular analyses including single-cell RNA sequencing were performed on the hearts of wild-type mice and EC-specific gene knockout mice. Metabolites in heart tissue were measured by capillary electrophoresis-time of flight-mass spectrometry system. The vaccine was prepared by conjugating the synthesized epitope peptides with keyhole limpet hemocyanin and administered to mice with aluminum hydroxide as an adjuvant. Tissue samples from heart failure patients were used for single-nucleus RNA sequencing to examine gene expression in ECs and perform pathway analysis in cardiomyocytes., Results: Pressure overload induced the development of intricately entwined blood vessels in murine hearts, leading to the accumulation of replication stress and DNA damage in cardiac ECs. Inhibition of cell proliferation by a cyclin-dependent kinase inhibitor reduced DNA damage in ECs and ameliorated transverse aortic constriction-induced cardiac dysfunction. Single-cell RNA sequencing analysis revealed upregulation of Igfbp7 (insulin-like growth factor-binding protein 7) expression in the senescent ECs and downregulation of insulin signaling and oxidative phosphorylation in cardiomyocytes of murine and human failing hearts. Overexpression of Igfbp7 in the murine heart using AAV9 (adeno-associated virus serotype 9) exacerbated cardiac dysfunction, while EC-specific deletion of Igfbp7 and the vaccine targeting Igfbp7 ameliorated cardiac dysfunction with increased oxidative phosphorylation in cardiomyocytes under pressure overload., Conclusions: Igfbp7 produced by senescent ECs causes cardiac dysfunction and vaccine therapy targeting Igfbp7 may be useful to prevent the development of heart failure., Competing Interests: The Department of Health Development and Medicine in Osaka University (H.H, H.N) is an endowed department supported by Anges, Daicel, and FunPep. The other authors report no conflicts.

Antisense oligonucleotides (ASOs) are generally obtained via chemical synthesis on a solid support and phosphorothioate (PS) modification with a phosphate backbone to increase their in vivo stability and activity. However, desulphurised products, in which PS is partially replaced by phosphodiesters, are generally formed during the chemical synthesis of ASO and are difficult to separate from the desired PS-modified ASO by chromatography. Therefore, revealing the unknown factors that cause the formation of desulphurised products and proposing methods to inhibit their formation are highly desirable. In this study, it was found that peroxides in THF, which is used as a solvent for the acetyl capping agent, oxidise phosphite triesters to produce desulphurisation products. The use of THF with antioxidants effectively suppresses the oxidation caused by THF peroxides. Moreover, THF peroxide was found to oxidise phosphoramidites, which are the building blocks of oligonucleotide chemical syntheses, indicating that caution should be taken with the organic solvents used during the synthesis and purification of phosphoramidites., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: Atrioventricular valve regurgitation in patients with univentricular heart is a well-known risk factor for adverse outcomes and atrioventricular valve repair remains a particular surgical challenge., Methods: We reviewed all surgical atrioventricular valve procedures in patients with univentricular heart and two separate atrioventricular valves who underwent surgical palliation. Endpoints of the study were reoperation-free survival and cumulative incidence of reoperation., Results: Between 1994 and 2021, 202 patients with univentricular heart and two separate atrioventricular valve morphology underwent surgical palliation, with 15.8% (32/202) requiring atrioventricular valve surgery. Primary diagnoses were double inlet left ventricle (n = 14, 43.8%), double outlet right ventricle (n = 7, 21.9%), and congenitally corrected transposition of the great arteries (n = 7, 21.9%). Median weight at valve surgery was 10.6 kg (interquartile range, 7.9-18.9). Isolated left or right atrioventricular valve surgery was required in nine (28.1%) and 22 patients (68.8%), respectively. Concomitant left and right atrioventricular valve surgery was performed in one patient (3.1%). Closure of the left valve was conducted in four patients (12.5%) and closure of the right valve in three (9.4%). Operative and late mortality were 3.1% and 9.7%, respectively. Reoperation-free survival and cumulative incidence of reoperation at 10 years after surgery were 62.3% (standard error of the mean: 6.9) and 30.9% (standard error of the mean: 9.6), respectively., Conclusions: In patients with univentricular heart and two separate atrioventricular valves, surgical intervention on these valves is required in a minority of patients and is associated with low mortality but high incidence of reoperation.

Background: Nivolumab plus ipilimumab (NIVO + IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). While approximately 40% of patients treated with NIVO + IPI achieve a durable response, 20% develop primary resistance with severe consequences. Therefore, there is a clinical need for criteria to select patients suitable for NIVO + IPI therapy to optimize its therapeutic efficacy. Accordingly, our aim was to evaluate the association between candidate biomarkers measured before treatment initiation and survival., Methods: This was a multi-institutional, retrospective, cohort study of 183 patients with mRCC treated with systematic therapies between August 2015 and July 2023. Of these, 112 received NIVO + IPI as first-line therapy: mean age, 68 years; men, 83.0% (n = 93), and clear cell histology, 80.4% (n = 90). Univariable and multivariable analyses were used to evaluate associations between biomarkers and survival., Results: On univariate analysis, high C-reactive protein and systemic index, a high neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio, and a low lymphocyte-to-monocyte ratio (LMR) were associated with shorter overall survival (OS). On multivariable analysis, a LMR ≤ 3 was retained as an independent factor associated to shorter OS with the highest accuracy (C-index, 0.656; hazard ratio, 7.042; 95% confidence interval, 2.0-25.0; p = 0.002)., Conclusion: A low LMR may identify patients who would be candidate for NIVO + IPI therapy for mRCC., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Aims: To clarify the impact of Breslow's scores consisting of only lifestyle habits or American Heart Association's (AHA) Life's Simple 7 scores consisting of lifestyle habits and control targets on starting dialysis in people with or without diabetes mellitus (DM)., Methods: To pursue the study aims, we examined a nationwide database on 294,647 individuals with and without DM aged 19-72 y in Japan to pursue the study aims. Using multivariate Cox modeling, we evaluated and compared 5 risk factors based on the unfavorable lifestyle factors in Breslow's scores and the unfavorable lifestyle factors and clinical values in AHA Life's Simple 7 scores., Results: DM increased the risk of the initiation of dialysis 5- to sixfold but that risk did not increase with worsening of Breslow risk factors. Compared with no risk factor, 5 risk factors derived from AHA's Life's Simple 7 presented 9.8-fold and 4.2-fold risks for the initiation of dialysis in non-DM and DM, respectively. In comparison with non-DM and no risk factor, risk of the initiation of dialysis dramatically increased up to 32.3 times according to the number of AHA risk factors in those with DM., Conclusions: DM and risk factors derived from AHA's Life's Simple 7 synergistically increased the risk of the initiation of dialysis. Factors similar to those used to predict cardiovascular disease would also be useful to predict the initiation of dialysis. These approaches might be helpful in clinical practice and patient education., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00739-0., Competing Interests: Conflict of interestAuthor Hirohito Sone received research funding and research grant from Novo Nordisk Pharma Ltd., Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. and Novartis Pharma K.K. Author Taeko Osawa, Author Kazuya Fujihara, Author Mayuko Harada Yamada, Author Yuta Yaguchi, Author Takaaki Sato, Author Masaru Kitazawa, Author Yasuhiro Matsubayashi, Author Takaho Yamada, and Author Satoru Kodama declare that they have no conflict of interest., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This study developed and validated a surgical instrument motion measurement system for skill evaluation during practical laparoscopic surgery training. Owing to the various advantages of laparoscopic surgery including minimal invasiveness, this technique has been widely used. However, expert surgeons have insufficient time for providing training to beginners due to the shortage of surgeons and limited working hours. Skill transfer efficiency has to be improved for which there is an urgent need to develop objective surgical skill evaluation methods. Therefore, a simple motion capture-based surgical instrument motion measurement system that could be easily installed in an operating room for skill assessment during practical surgical training was developed. The tip positions and orientations of the instruments were calculated based on the marker positions attached to the root of the instrument. Because the patterns of these markers are individual, this system can track multiple instruments simultaneously and detect exchanges. However due to the many obstacles in the operating room, the measurement data included noise and outliers. In this study, the effect of this decrease in measurement accuracy on feature calculation was determined. Accuracy verification experiments were conducted during wet-lab training to demonstrate the capability of this system to measure the motion of surgical instruments with practical accuracy. A surgical training experiment on a cadaver was conducted, and the motions of six surgical instruments were measured in 36 cases of laparoscopic radical nephrectomy. Outlier removal and smoothing methods were also developed and applied to remove the noise and outliers in the obtained data. The questionnaire survey conducted during the experiment confirmed that the measurement system did not interfere with the surgical operation. Thus, the proposed system was capable of making reliable measurements with minimal impact on surgery. The system will facilitate surgical education by enabling the evaluation of skill transfer of surgical skills., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ebina et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Rouse dynamics of polymer chains in model nanocomposite polyethylene oxide/silica nanoparticles (NPs) was investigated using quasielastic neutron scattering. The apparent Rouse rate of the polymer chains decreases as the particle loading increases. However, there is no evidence of an immobile segment population on the probed time scale of tens of ps. The slowing down of the dynamics is interpreted in terms of modified Rouse models for the chains in the NP interphase region. Thus, two chain populations, one bulk-like and the other characterized by a suppression of Rouse modes, are identified. The spatial extent of the interphase region is estimated to be about twice the adsorbed layer thickness, or ≈2 nm. These findings provide a detailed description of the suppression of the chain dynamics on the surface of NPs. These results are relevant insights on surface effects and confinement and provide a foundation for the understanding of the rheological properties of polymer nanocomposites with well-dispersed NPs.

We aimed to characterize the change in the incidence of stillbirth (IS) in Japanese Black cattle during and after animal movement restrictions and suspended insemination because of a foot-and-mouth disease (FMD) outbreak in Miyazaki Prefecture in 2010. Calving data from 2006 to 2018 were collected from approximately 900 farms. Post-FMD period was divided into three based on the median IS per month (1.80%): period 1 (May 2011 to February 2013), period 2 (March 2013 to August 2015), and period 3 (September 2015 to December 2018). The ISs were similar during the Pre-FMD period and Post-FMD period 1, then substantially decreased during Post-FMD period 2 (p < .05), before returning to the value before the FMD outbreak period during Post-FMD period 3. Compared with the Pre-FMD period, Post-FMD period 1 was associated with a higher proportion of calvings by primiparous cows and Post-FMD period 2 was associated with a smaller number of calvings per month (p < .05). There were high ISs in primiparous cows during the Pre-FMD period, Post-FMD period 1, and Post-FMD period 3 (p < .05), but not during Post-FMD period 2. In summary, after the animal movement restrictions and suspended insemination introduced because of the FMD outbreak, the IS temporarily decreased and consequently returned to the pre-FMD level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Misaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To identify early postoperative haemodynamic and laboratory parameters predicting outcomes following total cavopulmonary connection., Methods: Patients who underwent total cavopulmonary connection between 2012 and 2021 were evaluated. Serial values of mean pulmonary artery pressure, mean arterial pressure, peripheral oxygen saturation, and lactate levels were collected. The influence of these variables on morbidities was analyzed. Cut-off values were calculated using the receiver operating characteristic analysis., Results: A total of 249 patients were included. All patients had previous bidirectional cavopulmonary shunt. Median age and weight at total cavopulmonary connection were 2.2 (1.8-2.7) years and 11.7 (10.7-13.4) kg, respectively. All patients were extubated in the ICU at a median of 3 (2-5) hours after ICU admission. Postoperative pulmonary artery pressure, around 12 hours after extubation, was significantly associated with chest tube drainage (p = 0.048), chylothorax (p = 0.021), ascites (p = 0.016), and adverse events (p = 0.028). Receiver operating characteristic analysis revealed a cut-off value of 13-15 mmHg for chest tube drainage and chylothorax and 17 mmHg for ascites and adverse events. Mean arterial pressure 1 hour after extubation was associated with prolonged chest tube drainage (p = 0.015) and adverse events (p = 0.008). Peripheral oxygen saturation 6 hours after extubation (p = 0.003) was associated with chest tube duration and peripheral oxygen saturation 1 hour after extubation (p < 0.001) was associated with ascites. Lactate levels on 2 nd postoperative day (p = 0.022) were associated with ascites and lactate levels on 1 st postoperative day (p = 0.009) were associated with adverse events., Conclusions: Higher pulmonary artery pressure, lower mean arterial pressure, lower peripheral oxygen saturation, and higher lactate in early postoperative period, around 12 hours after extubation, predicted in-hospital and post-discharge adverse events following total cavopulmonary connection.

Objective: Glioma and meningioma require vastly different surgical approaches, even if only involving a simple craniotomy procedure. Diffusion weighted imaging (DWI) is useful for the postoperative evaluation of ischemic damage. The present study evaluated the expected but unproven differences in DWI findings., Methods: A total of 41 patients with meningiomas and 63 with gliomas met the inclusion criteria for adult cases with superficial lesions treated through simple supratentorial craniotomy. Postoperative DWI findings of DWI-positive rate, DWI-positive area type, and relationship with neurological deficits were evaluated., Results: The DWI-positive rate (P = 0.01) and the proportion of rim-type lesions (P < 0.01) were significantly more common in gliomas. Patients with meningiomas and DWI-positive areas presented with higher rates of new neurological deficits (P < 0.01), and patients with meningiomas on the left side were more likely to develop new neurological deficits (P = 0.02). Patients with gliomas tended to develop new deficits with larger DWI-positive area volumes (P = 0.04)., Conclusions: Postoperative early DWI-positive rate and rim-type lesions are more common after glioma resection than meningioma resection. Larger volumes of DWI-positive areas may be associated with postoperative neurological symptoms in gliomas. DWI-positive finding is less common after meningioma than glioma resection but more likely to be associated with new neurological symptoms. These differences are important for adequate postoperative DWI evaluation of common supratentorial brain tumors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Preventing dystocia can stabilise beef cattle management. This study aimed to investigate the relationship between serum pregnancy-associated glycoproteins (PAGs) S-N values and estrone sulphate (E 1 S) concentrations during pregnancy and the calf birth weight in beef cattle and to evaluate their usefulness as new predictive parameters for dystocia due to foetal overgrowth. Thirty-eight pregnant Japanese Black cattle were used. Blood samples were collected at 40, 70, 100, 150, 200, 250, 280, and 285 days after artificial insemination (AI), and birth weight of the offspring was measured. Serum PAGs S-N values and E 1 S concentrations were measured, and the area under the curve (AUC) and the ratio of change based on 70 days after AI were calculated, followed by calculation of the correlation coefficient with the birth weight of the offspring and comparison between the eutocia (n = 32) and dystocia (n = 6) groups. The birth weight of the offspring was moderately positively correlated with the AUC of serum PAGs S-N values and E 1 S concentrations in the second (r = 0.425, P < 0.01) and third (r = 0.595, P < 0.01) trimesters, respectively. The ratio of change in serum E 1 S concentrations between 70 and 280 days after AI was greater (P < 0.05) in the dystocia group (1276.6 ± 229.1 %) than in the eutocia group (852.6 ± 69.6 %). These results suggest that blood PAGs S-N values at mid-pregnancy (100-199 days after AI) and the ratio of changes in blood E 1 S concentrations between 70 and 280 days after AI may be new parameters for predicting dystocia., Competing Interests: Declaration of Competing Interest None of the authors have any financial or personal relationships that could inappropriately influence or bias the content of this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To achieve patient-centricity in metastatic renal cell carcinoma (mRCC) treatment, it is essential to clarify the differences in perspectives between patients and physicians. This cross-sectional analysis of a web survey aimed to clarify the differences in expectations and concerns between mRCC patients and physicians regarding systemic mRCC therapy in Japan., Methods: Surveys from 83 patients and 165 physicians were analyzed., Results: The top three most significant differences in expectations of systemic therapy between patients and physicians (patient-based physician value) were "Chance of achieving treatment-free status" (-30.1%, p < 0.001), "Longer survival" (+25.8%, p < 0.001), and "Chance of eliminating all evidence of disease" (-25.6%, p < 0.001). The top three most significant differences in concerns for systemic therapy between patients and physicians (patient-based physician value) were "Lack of efficacy" (+36.1%, p < 0.001), "Lack of knowledge of treatment" (-28.2%, p < 0.001), and "Daily activities affected by side effects" (+22.3%, p < 0.001). Diarrhea, fatigue/malaise, and nausea/vomiting were patients' most distressing adverse events; 50.6% of patients had difficulty telling their physicians about adverse events such as fatigue, anxiety, and depression., Conclusions: This study demonstrated a gap between patients with mRCC and physicians in their expectations and concerns for systemic therapy. Japanese patients with mRCC suffer from a number of adverse events, some of which are not shared with physicians. This study highlights the importance of communicating well with patients in clinical practice to achieve patient-centricity in systemic treatment for mRCC., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The fastening mechanics of prosthetic screws under various conditions is crucial to the maintenance of dental implants. This study comprehensively explores the prosthetic screw rupture in titanium (Ti) and zirconia (ZrO 2 ) superstructures under wet and dry conditions. Superstructures were fabricated using digital technology and subjected to tightening torque trials. Experimental results suggested that the implications of the conventionally recommended torque of 15 N•cm differ significantly between dry and wet environments. Both Ti and ZrO 2 exhibited preloads of >30 N•cm under dry conditions; however, differences emerged under wet conditions. In addition, screw rupture posed a prominent clinical challenge -particularly during long-term cyclic loading. Notably, the ZrO 2 superstructures exhibited a greater resistance to breaking torque than that of Ti. This study underscores the importance of reevaluating torque recommendations with consideration to the distinct characteristics of Ti and ZrO 2 in diverse environments.

Information on the financial toxicity experienced by Japanese patients with metastatic renal cell carcinoma (mRCC) is lacking, even though Japan has its own unique public health insurance system. Thus, a web-based survey was conducted to evaluate the financial toxicity experienced by Japanese mRCC patients using the COmprehensive Score for financial Toxicity (COST) tool. This study enrolled Japanese patients who underwent, or were undergoing, systemic therapy for mRCC. The outcomes evaluated were the distribution of COST scores, the correlation between COST and quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) scale, and demographic factors associated with financial toxicity. The median (range) COST score was 19.0 (3.0-36.0). The Pearson correlation coefficient for COST and FACT-G total scores was 0.40. Univariate analysis revealed that not having private health insurance and lower household income per year were significantly associated with lower COST scores. Multivariate analyses showed that age < 65 years and not having private health insurance were significantly associated with lower COST scores. This study revealed that Japanese mRCC patients experience adverse financial impacts even under the universal health insurance coverage system available in Japan, and financial toxicity negatively affects their QOL.

Subclinical endometritis affects reproductive outcomes and causes economic losses in dairy cows, thus, it is important to understand disease progression mechanisms and develop diagnostic procedures for better disease management. We measured the levels of 146 lipid mediators in uterine flush samples using lipid chromatography-mass spectrometry. We detected 25 lipid mediators in the uterine flush of both the control and subclinical endometritis cows; 15 of the 25 lipid mediators were AA-derived metabolites. Among the AA-derived metabolites, cyclooxygenase (COX)-generated mediators were the most abundant. Specifically, levels of 11β-13,14-dihydro-15-keto prostaglandin (PG) F 2α , PGE 2 , PGA 2 , 13-hydroxyoctadecadienoic acid, and PGD 1 were elevated in all the cows with subclinical endometritis. This study may provide new insights for the management of subclinical bovine endometritis.

Objectives: This study aimed to assess the prognostic outcomes in mRCC patients receiving second-line TKI following first-line IO combination therapy., Methods: This study retrospectively included 243 mRCC patients receiving second-line TKI after first-line IO combination therapy: nivolumab plus ipilimumab (n = 189, IO-IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n = 54, IO-TKI group). Oncological outcomes between the two groups were compared, and prognostication systems were developed for these patients., Results: In the IO-IO and IO-TKI groups, the objective response rates to second-line TKI were 34.4% and 25.9% (p = 0.26), the median PFS periods were 9.7 and 7.1 months (p = 0.79), and the median OS periods after the introduction of second-line TKI were 23.1 and 33.5 months (p = 0.93), respectively. Among the several factors examined, non-CCRCC, high CRP, and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c-indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC, and MSKCC systems, respectively., Conclusions: There were no significant differences in the prognostic outcomes after introducing second-line TKI between the IO-IO and IO-TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second-line TKI, irrespective of first-line IO combination therapies., (© 2024 The Japanese Urological Association.)

We established a transition program from hospital to home administration of blinatumomab using the CADD-Legacy® pump and evaluated its safety and feasibility in 2 pediatric patients. The program recommended that repeated overnight stays with continued hospitalization would help patients safely transition to home administration of blinatumomab. Pediatric patients who do not attend school, such as preschoolers, or who return to their original school, can be transited to an outpatient setting if people caring for pediatric patients, including teachers in the school, are educated.

Highly polar and charged molecules, such as oligonucleotides, face significant barriers in crossing the cell membrane to access the cytoplasm. To address this problem, we developed a light-triggered twistable tetraphenylethene (TPE) derivative, TPE-C-N, to facilitate the intracellular delivery of charged molecules through an endocytosis-independent pathway. The central double bond of TPE in TPE-C-N is planar in the ground state but becomes twisted in the excited state. Under light irradiation, this planar-to-twisted structural change induces continuous cell membrane disturbances. Such disturbance does not lead to permanent damage to the cell membrane. TPE-C-N significantly enhanced the intracellular delivery of negatively charged molecules under light irradiation when endocytosis was inhibited through low-temperature treatment, confirming the endocytosis-independent nature of this delivery method. We have successfully demonstrated that the TPE-C-N-mediated light-controllable method can efficiently promote the intracellular delivery of charged molecules, such as peptides and oligonucleotides, with molecular weights ranging from 1000 to 5000 Da.

Objectives: Previous studies suggested that living kidney donors do not have a higher risk of death or kidney failure than the general population. However, living kidney donor risk is controversial. Furthermore, only a few studies have evaluated long-term kidney function after kidney donation., Methods: This study evaluated Japanese kidney donor' long-term outcomes, including mortality and kidney function. From 1965 to 2015, 230 donors (76 males, 154 females, and a median age of 54) were enrolled in this study. The median observation period was 11.0 (range, 0.3-41.0) years., Results: In total, 215 donors were still alive, and 15 had died. Causes of death included malignancies, cardiovascular disease, pneumonia, suicide, gastrointestinal bleeding, and kidney failure. Actual donor survival rates at 10, 20, and 30 years were 95.3%, 90.7%, and 80.9%, respectively. These values were comparable to age- and gender-matched expected survival. Long-term kidney function after donation was evaluated in 211 donors with serum creatinine data. Two donors developed kidney failure 24 and 26 years post-donation, respectively. The percentage of donors whose estimated glomerular filtration rate (eGFR) remained ≥45 mL/min/1.73 m 2 at 10, 20, and 30 years after donation were 84.2%, 73.0%, and 63.9%, respectively. Survival rates of donors with eGFR <45 mL/min/1.73 m 2 were comparable to those in persons with eGFR >45 mL/min/1.73 m 2 ., Conclusion: Our findings revealed that kidney donors did not have a higher long-term risk of death than the general population. Although some donors showed decreased kidney function after donation, kidney function did not impact their survival., (© 2024 The Japanese Urological Association.)

The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3-methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography-mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2-penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors (MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high-risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

New technologies such as laparoscopic and robotic surgery are spreading, and there is a demand for physicians to keep up with novel methods. In contrast to the recent focus on healthcare professional burnout, the mental and physical costs during surgery are not well-understood. We aimed to quantify surgeons' workloads in daily urological surgical practice and clarify potential background factors associated with such workloads. Urologists in Hokkaido, Japan, were invited to this study. Between December 2020 and December 2021, participants repeatedly reported workloads, which were assessed using the National Aeronautics and Space Administration-Task Load Index (NASA-TLX), after each surgery in conjunction with participants' names, patients' backgrounds, their roles (independent operator, operator under supervision, instructor, and 1st or 2nd assistant), and surgical outcomes, via SurveyMonkey ® . Because of the heterogeneity among individuals, a linear mixed-effects model was utilized to analyze factors associated with NASA-TLX, calculating the parameter estimates (PE) of regression coefficients for each factor and their 95% confidence interval (CI). Sixty-five urologists (5 women) joined the study, and 2169 data were collected within 7 days after surgeries. A linear mixed-effects model revealed that female surgeons (PE + 15.56, 95% CI 2.36-28.77), urgent/emergency surgery (PE + 6.65, 95% CI 4.59-8.70), intraoperative complications (PE + 9.26, 95% CI 6.76-11.76), and near-miss incidents (PE + 3.81, 95% CI 2.27-5.36) were associated with higher workloads. Regarding the surgeons' role, operator under supervision (PE + 12.46, 95% CI 9.86-15.06) showed the highest workloads. Surgeons' workloads decreased as the number of previous cases of the same procedure increased. Surgeons' workloads were associated with various factors. Given that the highest workloads were for operators under supervision, instructors should be aware of trainees' high workloads and devise appropriate instructional interventions., (© 2024. The Author(s).)

Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in clinical applications for the amelioration of immune disorders, including graft-versus-host disease (GvHD) and Crohn's disease. The immunosuppressive role of Programmed death-ligand 1 (PD-L1) in MSCs is pivotal, yet the regulatory mechanisms governing its expression remain to be fully elucidated. In this study, we explored the influence of paired-related homeobox (PRRX1), a determinant of multipotency and self-renewal in MSCs, on the expression of various surface antigens, notably PD-L1. Multiple isoforms of PRRX1 were found to augment the mRNA levels of MSC markers, such as CD26 and CD317, with all isoforms elevating PD-L1 expression at both mRNA and protein levels. This study reveals that PRRX1 may act as a potential immunomodulatory factor in MSCs by regulating the PD-L1 pathway., (© 2024. The Author(s).)

Background: Owing to the minimally invasive nature of transcatheter aortic valve replacement (TAVR), TAVR seems to be preferred in patients with cancer; however, related research on the clinical efficacy and safety of TAVR in patients with cancer and severe aortic stenosis is limited, and conclusions are controversial. This study aimed to evaluate the clinical outcomes of patients with cancer who underwent TAVR., Method and Results: We conducted a systematic review and meta-analysis to investigate the clinical outcomes in patients with and without cancer who underwent TAVR. We systematically reviewed and analyzed 15 studies (195,658 patients) published in PubMed and Cochrane Library databases between January 2022 and January 2023. The primary outcomes were short-term (in-hospital or 30-day) and long-term (≥12 months) mortality. The prevalence of current or previous cancer in the patients undergoing TAVR was 19.8 % (38,695 patients). Patients with cancer had a lower risk of short-term mortality (odds ratio [OR] 0.69, 95 % confidence interval [CI] 0.61-0.77, P < 0.001) but a higher risk of long-term mortality (OR 1.54, 95 % CI 1.35-1.76, P < 0.001) than those without cancer. Patients with cancer had a lower incidence of postprocedural stroke and acute kidney injury but a higher incidence of pacemaker implantation than patients without cancer., Conclusions: Patients with cancer undergoing TAVR have a good short-term prognosis and acceptable perioperative complications compared with patients without cancer. However, the long-term outcomes are contingent on cancer survival., Competing Interests: 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., (© 2024 The Author(s).)

Aims: To evaluate and compare the association of incident cardiovascular disease (CVD) with the Health Practice Index (HPI) reflecting only lifestyle habits and Ideal Cardiovascular Health Metrics (ICVHMs) consisting of lifestyle habits and factors targeted for control in the same population according to glucose status., Methods: This retrospective cohort study included 1,28,162 participants aged 18-72 years with no history of CVD followed for ≥ 3 years between 2008 and 2016. Participants were classified according to normal glucose tolerance (86,174), prediabetes (36,096), or diabetes (5892). HPI and ICVHMs scores were classified into three groups (high/medium/low). Multivariate Cox regression hazard analysis examined CVD risk., Results: During a mean follow-up of 5.2 years, 1057 CVD events occurred. In prediabetes, CVD risk was significantly higher in groups with both medium and low HPI scores and ICVHMs scores compared to high scores for normal glucose tolerance (hazard ratios [HRs] for high/medium/low HPI scores were 0.95 [0.78-1.17], 1.56 [1.29-1.89], and 2.41 [1.74-3.34] and for ICVHMs scores were 0.74 [0.50-1.11], 1.58 [1.26-1.98], and 2.63 [2.10-3.31], respectively). Regarding diabetes, compared with high HPI/ICVHMs scores in the normal glucose tolerance group, a significantly increased CVD risk was observed in the high-score HPI group, but not in the high-score ICVHMs group (HPI high/medium/low HR, 1.63 [1.22-2.18], 2.19 [1.69-2.83], and 2.26 [1.34 -3.83]; ICVHMs high/medium/low HR, 1.14 [0.47-2.81], 2.38 [1.75-3.23], and 3.31 [2.50-4.38], respectively)., Conclusions: In diabetes, ideal lifestyle practices alone were insufficient for primary prevention of CVD but had a greater impact on primary prevention of CVD in prediabetes., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00708-7., Competing Interests: Conflict of interestThe authors declare that there is no duality of interest associated with this manuscript., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Saxitoxin (STX, 1) is a representative compound of paralytic shellfish toxins (PSTs) that are produced by marine dinoflagellates and freshwater cyanobacteria. Although several pathways have been proposed for the biosynthesis of STX, the order of ring and side chain hydroxylation, and formation of the tricyclic skeleton have not been well established. In this study, 12,12-dideoxy-decarbamoyloxySTX (dd-doSTX, 2), the most reduced STX analogue having the tricyclic skeleton, and its analogues, 12β-deoxy-doSTX (12β-d-doSTX, 3), 12α-deoxy-doSTX (12α-d-doSTX, 4), and doSTX (5), were synthesized, and these compounds were screened in the toxic microalgae using high-resolution LCMSMS. dd-doSTX (2) and 12β-d-doSTX (3) were identified in the PSTs-producing dinoflagellates (Alexandrium catenella, A. pacificum, and/or Gymnodinium catenatum) and in the cyanobacterium Dolichospermum circinale (TA04). doSTX (5), previously isolated from the dinoflagellate G. catenatum, was also identified in D. circinale (TA04). Furthermore, the conversion of 2 to 3, and 4 to 5, by SxtT with VanB, a reported Rieske oxygenase and its redox partner in STX biosynthesis, was confirmed. These results support that 2 is a possible biosynthetic precursor of STX, and that ring and side-chain hydroxylations proceed after cyclization., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

We designed this multi-center prospective study with the following objectives: (1) the cross-sectional validation of extracellular vesicles (EV) mRNA markers to detect urothelial bladder cancer (UBC) before transurethral resection of bladder cancer (TURBT), and (2) the longitudinal validation of EV mRNA markers to monitor non-muscle invasive bladder cancer (NMIBC) recurrence after TURBT. EV mRNA markers evaluated in this study were KRT17, GPRC5A, and SLC2A1 in addition to two additional markers from literatures, MDK and CXCR2, and measured by quantitative RT-PCR with normalization by a reference gene (ALDOB). Diagnostic performances of EV mRNA markers were compared to conventional markers. Regarding the first objective, we confirmed that EV mRNA biomarkers in urine were higher in UBC patients, particularly those with higher stage/grade tumors, than in those without UBC (n = 278 in total) and the diagnostic performance of EV mRNA MDK and KRT17 outperformed conventional biomarkers with AUC 0.760 and 0.730, respectively. Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p < 0.01)., (© 2024. The Author(s).)

In the 3' untranslated region of the SARS-CoV-2 virus RNA genome, genomic RNA replication is initiated in the highly conserved region called 3'PK, containing three stem structures (P1pk, P2, and P5). According to one proposed mechanism, P1pk and distal P2 stems switch their structure to a pseudoknot through base-pairing, thereby initiating transcription by recruiting RNA-dependent RNA polymerase complexed with nonstructural proteins (nsp)7 and nsp8. However, experimental evidence of pseudoknot formation or structural switching is unavailable. Using SARS-CoV-2 3'PK fragments, we show that 3'PK adopted stem-loop and pseudoknot forms in a mutually exclusive manner. When P1pk and P2 formed a pseudoknot, the P5 stem, which includes a sequence at the 3' end, exited from the stem-loop structure and opened up. Interaction with the nsp7/nsp8 complex destabilized the stem-loop form but did not alter the pseudoknot form. These results suggest that the interaction between the pseudoknot and nsp7/nsp8 complex transformed the 3' end of viral genomic RNA into single-stranded RNA ready for synthesis, presenting the unique pseudoknot structure as a potential pharmacological target., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Aims: Although conventional interventions for people at high risk of developing type 2 diabetes are usually conducted face-to-face, such interventions are burdensome for health care providers. We developed a lifestyle intervention program combining lifestyle coaching via a smartphone application augmented by intermittently scanned continuous glucose monitoring without burdening health care providers. Its effectiveness for glycemic control and body weight reduction in people at risk of type 2 diabetes was investigated., Materials and Methods: For this 12-week randomized unblinded trial with offline recruitment, participants with a hemoglobin A1c level of 5.6% to 6.4% or a fasting blood glucose of 110 to 125 mg/dL and body mass index (BMI) >23 kg/m2 but <40 kg/m2 were randomly assigned to the intervention group (App) and control group (C). The primary endpoint was the difference in time in range of blood glucose between 70 and 140 mg/dL (3.9-7.8 mmol/L) before and after the study period between the 2 groups., Results: Among 168 patients (mean age, 48.1 years; mean BMI, 26.6 kg/m2; and male, 80.4%), 82 and 86 were assigned to the App group and C group, respectively. After 12 weeks, time in range of blood glucose at 70 to 140 mg/dL significantly improved in the App group compared with the C group (-2.6 minutes/day vs +31.5 minutes/day, P = .03). Changes in time above range did not differ, whereas time below range (blood glucose <70 mg/dL; +23.5 minutes/day vs -8.9 minutes/day, P = .02) improved in the App group. BMI (-0.26 vs -0.59, P = .017) was reduced in the App group compared with the C group., Conclusion: Intervention with a smartphone app and intermittently scanned continuous glucose monitoring increased glycemic control accompanied by decreased carbohydrate intake and weight loss. Further trials are needed to confirm whether these interventions can reduce incident type 2 diabetes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)