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Abstract For prostate cancer patients who experience biochemical progression during androgen deprivation therapy (ADT), prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has not been prospectively compared to planar bone scan plus CT. This was a single-arm, head-to-head, prospective phase II trial (NCT04928820) designed to enroll 102 men with prostate cancer who experienced biochemical progression (rising prostate-specific antigen [PSA] ≥ 1 ng/mL) during ADT. All patients received 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scans. Each scan was interpreted by three central independent readers. The primary endpoint was the per-patient bone metastasis detection rate of PSMA PET/CT versus planar bone scan and CT. Secondary endpoints compared the number of bone metastases detected per patient and the inter-reader agreement of each imaging modality. Twenty-two men were enrolled between July 2021 and June 2022. Due to slow accrual following approval of PSMA PET radiotracers in the U.S. and a lack of a statistical signal between the two imaging modalities on interim analysis, this trial was closed early on October 2022. Median PSA was 8.5 ng/mL (interquartile range: 1.6–77.6). There was 100% agreement between the two scans. Six patients (27%) had negative findings and 16 patients (73%) had positive findings on both scans. PSMA PET/CT and bone scan plus CT detected an equal number of bone lesions for 14 patients (64%), PSMA PET/CT detected more bone lesions for six patients (27%), and bone scan plus CT detected more bone lesions for two patients (9.1%) (p = 0.092). The inter-reader agreement rates of PSMA PET/CT and bone scan plus CT were 96% and 82%, respectively (p = 0.25). In men with biochemical progression during ADT, 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scan plus CT had identical bone metastasis detection rates. Bone scan plus CT can continue to serve as a cost-effective and readily accessible restaging modality in patients with biochemical progression. ClinicalTrials.gov NCT04928820. Registered 16/06/2021.

Abstract Background Biological age, especially epigenetic age derived from the epigenetic clock, is a significant measure of aging, considering the differences in aging rates among individuals. The epigenetic clock, a machine learning-based algorithm, uses DNA methylation states to estimate biological age. Previous studies have reported inconsistent associations between physical activity (PA) and the epigenetic clock, especially second-generation clocks such as PhenoAge and GrimAge. This study aimed to clarify this relationship using cross-sectional data from Japanese participants aged 40–69. Methods We used two datasets from the Saga J-MICC study, of which 867 samples were available for analysis. DNA methylation data from peripheral blood samples were used to calculate the epigenetic age using the epigenetic clocks PhenoAge and GrimAge. PA and sedentary time were measured using a single-axis accelerometer, while self-reported PA, sedentary time, and covariates were assessed using a self-administered questionnaire. The association between PA or sedentary time and epigenetic age acceleration was assessed using multiple linear regression. Results Pearson's correlation coefficients between accelerometer-based and self-reported PA variables ranged from 0.09 to 0.20. Multivariable regression analysis showed that accelerometer-based PA and sedentary time were associated with epigenetic age decelerations and accelerations, respectively. However, self-reported PA was not associated with the epigenetic age accelerations. Conclusions These results indicate that reducing sedentary time and increasing PA were associated with slowing both PhenoAge and GrimAge, even in East Asian populations with different exercise habits, body shapes, and lifestyles. This study highlights the potential of objective second-generation epigenetic age acceleration as an outcome index for healthcare interventions and clinical applications.

Abstract In mammalian cells, protein condensates underlie diverse cell functions. Intensive synthetic biological research has been devoted to fabricating liquid droplets using de novo peptides/proteins designed from scratch in test tubes or bacterial cells. However, the development of de novo sequences for synthetic droplets forming in eukaryotes is challenging. Here, we report YK peptides, comprising 9–15 residues of alternating repeats of tyrosine and lysine, which form reversible amyloid-like fibrils accompanied by binding with poly-anion species such as ATP. By genetically tagging the YK peptide, superfolder GFPs assemble into artificial liquid-like droplets in living cells. Rational design of the YK system allows fine-tuning of the fluidity and construction of multi-component droplets. The YK system not only facilitates intracellular reconstitution of simplified models for natural protein condensates, but it also provides a toolbox for the systematic creation of droplets with different dynamics and composition for in situ evaluation.

Abstract Background Pancreaticoduodenectomy is a highly difficult and invasive type of gastrointestinal surgery. Prevention of postoperative pancreatic fistula is important, and this may be possible by the stapler method. Methods STRAP-PD is a single center randomized controlled trial. We compare a method of transecting the pancreatic parenchyma in pancreaticoduodenectomy using a surgical stapler device with a conventional transecting method using energy devices (e.g., scalpel, ultrasonic coagulator and incision devices). Patients with soft pancreas who are scheduled to undergo pancreaticoduodenectomy are randomized to arm A (conventional method) or arm B (stapler method). We aim to examine the safety and usefulness of dissection by the automatic suture device, with attention to the rate of pancreatic fistula ISGPF grade B or C and to postoperative complications. This is a single-center randomized study, which began in September 2023 at Wakayama Medical University Hospital. Discussion Pancreatic parenchymal transection is typically performed either by direct incision using a scalpel or by employing energy devices such as ultrasonic coagulating cutting devices during pancreaticoduodenectomy. In a prospective pilot study, we conducted pancreatic parenchymal transection in 20 consecutive normal pancreatic cases during pancreaticoduodenectomy, observing postoperative pancreatic fistula grade B in one case (5%). Traditional methods involving scalpel incision or the use of ultrasonic coagulating cutting devices have been historically favored but perceived as technically challenging, and they have been reliant upon the surgeon's skill. Notably, relatively high incidences of postoperative pancreatic fistula among patients with soft pancreas have also been observed. Our proposed stapler method may therefore be a useful method responsible for reducing the development of pancreatic fistula. This method would be as part of minimally-invasive surgery for pancreaticoduodenectomy. It uses an endoscopic linear stapler to cut the pancreatic parenchyma, so it is likely to be more convenient than conventional methods and can be used universally. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000052089. the Registration Date on 1st September 2023.

Abstract Aims This study aimed to describe baseline characteristics and adherence among patients with transthyretin amyloid cardiomyopathy (ATTR‐CM) treated with tafamidis (VYNDAQEL®) in Japan using the Japanese Medical Data Vision (MDV) database. Methods and results This study was a non‐interventional, retrospective cohort study of adult (≥18 years old) patients in the Japanese MDV claims database diagnosed with ATTR‐CM and with at least two tafamidis prescriptions of dose strength 4 × 20 mg/day between 1 March 2019 and 31 August 2021. The date of the first prescription was defined as the index date, with follow‐up time defined as the time between the first and last prescription plus the days' supply from the last refill. Baseline characteristics were assessed during a 12 month pre‐index period. Adherence was measured using two metrics: (i) the modified medication possession ratio (mMPR), calculated by taking the sum of days supplied for all fills within the follow‐up period, divided by the number of days of follow‐up, and reported as a percentage, with patients classified as adherent with an mMPR of ≥80%, and (ii) the proportion of days covered (PDC), calculated by taking the total number of days' supply dispensed during the follow‐up period divided by the number of days of follow‐up, adjusting for any days' supply overlap. A total of 210 patients were identified; the mean (standard deviation) age of the cohort was 77 (5.9) years, and the majority (89%) were male. The most common baseline cardiovascular comorbidities were heart failure (85%), ischaemic heart disease (66%), hypertensive diseases (49%), and diabetes (35%); 75% of patients received heart failure medications in the 12 months prior to index, with the most common being beta‐blockers (49%), diuretics (48%), angiotensin receptor blockers (30%), angiotensin‐converting enzyme inhibitors (22%), and sodium–glucose cotransporter‐2 inhibitors (8.1%). Over an average 14 month follow‐up, mean mMPR was 96% with a median of 100% [inter‐quartile range (IQR): 97–101%]; 93% of patients were adherent (defined as an mMPR ≥ 80%). In the same follow‐up period, mean PDC was 93.6% with a median of 99% (IQR: 93–100%). Persistence was high with 78% of patients having a 0 day gap between prescription refills. Conclusions This study found high adherence rates to tafamidis in this real‐world Japanese patient population. Adherence rates in this study were similar to those reported by the tafamidis clinical trial and a previously published US commercial claims adherence analysis. Further studies should be conducted to assess the impact of real‐world adherence on real‐world outcomes.

This study compared the 1-year clinical outcomes and disc degeneration rates after transforaminal full-endoscopic lumbar discectomy (TF-FED), condoliase injection, open discectomy (OD), and microendoscopic discectomy (MED) for lumbar disc herniation (LDH). In total, 279 patients with LDH were divided into four treatment groups: TF-FED, OD, MED, and condoliase injection. Outcomes were evaluated on the basis of the complication rate, Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), visual analog scale (VAS) scores, and the modified MacNab criteria. Surgical and hospital costs were assessed. Disc degeneration and endplate bone marrow edema were evaluated using magnetic resonance images. The mean postoperative JOABPEQ, VAS, or modified MacNab scores among the four groups had no significant differences. Additionally, the nerve injury or reoperation rate among the TF-FED, OD, and MED groups had no significant difference. However, the reoperation rate with condoliase injection was high because of residual disc herniation. Surgical and hospital costs were lower with condoliase injection and higher with OD and MED than those with TF-FED. With TF-FED and condoliase injection, the Pfirrmann grade progressed, and the disc height was significantly smaller than that with OD and MED. Endplate bone marrow edema was more common with condoliase injection and TF-FED. All groups had good outcomes. TF-FED and condoliase injection may reduce the burden of surgery because they can be performed under local anesthesia with little blood loss and low medical costs but tend to be associated with disc degeneration and endplate bone marrow edema. A randomized controlled study with a larger sample is needed.

Introduction: Few studies have assessed the minimum clinically important difference (MCID) of each Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) domain. This study assessed MCIDs of JOABPEQ in patients with lumbar spine disease by generation. Methods: We evaluated the JOABPEQ score of 805 consecutive patients with lumbar spine disease undergoing posterior surgery preoperatively and 1 year postoperatively. MCIDs of each JOABPEQ domain were determined using anchor- and distribution-based methods according to age. A question based on the concept of a health transition item was used as the anchor for the MCID decision. Results: Overall, MCIDs of the JOABPEQ were 28.6 and 27.3 points for pain-related disorder and gait disturbance, respectively. The MCID for the lumbar spine dysfunction domain did not reach 0.6 over the area under the curve. Regarding the differences among generations, MCIDs of pain-related disorder and gait disturbance domains differed slightly between the elderly and middle-aged. The psychological disorder domain did not reflect clinically meaningful changes in the elderly. MCIDs of the social life disturbance domain decreased with age. Conclusions: Focusing on achieving the ideal responsiveness of patient-reported outcomes across generations, MCIDs of the pain-related disorder and gait disturbance domains may be valuable for patients, regardless of age, when adopting the JOABPEQ for patients with lumbar spine disease undergoing surgery. This study only evaluated cases that underwent posterior lumbar surgery. Future research will necessitate conducting surveys concerning the outcomes of various treatments for lumbar spine disease.

Abstract Pelvic organ prolapse (POP) affects approximately 40% of elderly women, characterized by the descent of the pelvic organs into the vaginal cavity. Here we present the results of a genome-wide association study (GWAS) for susceptibility to POP comprising 771 cases and 76,625 controls in the Japanese population. We identified a significant association of WT1 locus with POP in the Japanese population; rs10742277; odds ratio (OR) = 1.48, 95% confidence interval (CI), 1.29–1.68, P = 6.72 × 10− 9. Subsequent cross-ancestry GWAS meta-analysis combining the Japanese data and previously reported European data, including 28,857 cases and 622,916 controls, identified FGFR2 locus as a novel susceptibility locus to POP (rs7072877; OR = 1.06, 95% CI, 1.04–1.08, P = 4.11 × 10− 8). We also observed consistent directions of the effects for 21 out of 24 European GWAS derived loci (binomial test P = 2.8 × 10− 4), indicating that most of susceptibility loci for POP are shared across the Japanese and European populations.

Background/Aims Although endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is performed globally, the procedure remains challenging. Guidewire manipulation is the most difficult step, and there are few reports on the factors associated with unsuccessful guidewire manipulation. This study aimed to assess the significance of the puncture angle on EUS images and identify the most effective guidewire rescue method for patients with unsuccessful guidewire manipulation. Methods We retrospectively enrolled 115 patients who underwent EUS-HGS between May 2016 and April 2022 at two centers. The puncture angle between the needle and the intrahepatic bile duct was measured through EUS movie records. Results Guidewire manipulation was unsuccessful in 28 patients. Receiver operating characteristic (ROC) curves identified an optimal puncture angle cutoff value of 85° (cutoff value, 85°; area under the ROC curve, 0.826; sensitivity, 85.7%; specificity, 81.6%). Multivariate analysis demonstrated that a puncture angle

This study introduces an innovative technique that merges computer vision with topology optimization to advance additive manufacturing. Employing advanced photogrammetry software, we obtain high-resolution images of the design domain, which are then used to develop accurate 3D models through meticulous scanning procedures. These models are transformed into an STL file format and remeshed using an adaptive algorithm within COMSOL 5.3 Multiphysics, facilitated by a custom MATLAB 2023 application. This integration achieves the optimal mesh resolution and precision in analytical assessments. We applied this technique to the design of a concrete pillar for 3D printing, targeting a 75% reduction in volume to improve the material efficiency and structural stability—critical factors for extraterrestrial applications. The design, captured with a 360-degree camera array, guided the MATLAB-based topology optimization process. By combining MATLAB’s optimization algorithms with COMSOL’s meshing and finite element analysis tools, we investigated various material-efficient configurations. The findings reveal a substantial volume reduction, especially in the central region of the design, effectively optimizing material utilization while preserving structural integrity. The optimization algorithm exhibited a swift and stable convergence, reaching near-optimal solutions within approximately 20 iterations.

Abstract Background The predictive power of the treatment efficacy and prognosis in primary androgen deprivation therapy (ADT) for advanced prostate cancer is not satisfactory. The objective of this study was to integrate genetic and clinical data to predict castration resistance in primary ADT for advanced prostate cancer by machine learning (ML). Methods Clinical and single nucleotide polymorphisms (SNP) data obtained in the KYUCOG-1401-A study (UMIN000022852) that enrolled Japanese patients with advanced prostate cancer were used. All patients were treated with primary ADT. A point-wise linear (PWL) algorithm, logistic regression with elastic-net regularization, and eXtreme Gradient Boosting were the ML algorithms used in this study. Area under the curve for castration resistance and C-index for prognoses were calculated to evaluate the utility of the models. Results Among the three ML algorithms, the area under the curve values to predict castration resistance at 2 years was highest for the PWL algorithm with all the datasets. Three predictive models (clinical model, small SNPs model, and large SNPs model) were created by the PWL algorithm using the clinical data alone, and 2 and 46 SNPs in addition to clinical data. C-indices for overall survival by the clinical, small SNPs, and large SNPs models were 0.636, 0.621, and 0.703, respectively. Conclusion The results demonstrated that the SNPs models created by ML produced excellent prediction of castration resistance and prognosis in primary ADT for advanced prostate cancer, and will be helpful in treatment choice.

Abstract Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. The study population included individuals from both Eastern and Western regions with a confirmed diagnosis of HCC and receiving first line treatment with Atezolizumab plus bevacizumab or Lenvatinib. Univariate and multivariate analyses were performed by Cox proportional. For the analysis, patients were stratified based on their use of concomitant medication or not. At the time of database lock, 319 deaths were observed: 209 in the Lenvatinib cohort, 110 in the Atezolizumab plus bevacizumab cohort. In the Atezolizumab plus Bevacizumab arm, 50 (16.5%) patients were on chronic metformin use. At the univariate analysis for OS, patients who used metformin showed significantly shorter OS compared to patients who did not use metformin (HR 1.9, 95% CI 1.1–3.2). Multivariate analysis confirmed that patients in metformin group had significantly shorter OS compared to patients in no-metformin group (HR 1.9; 95% CI 1.1–3.1). At the univariate analysis for PFS, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.6, 95% CI 1.0–2.6). Multivariate analysis confirmed that patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.7; 95% CI 1.1–2.7; p = 0.0147). No differences were reported in terms of ORR and DCR between patients in metformin group and those in no-metformin group. In the Lenvatinib cohort, 65 (15%) patients were recorded to chronically use metformin. No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group. This analysis unveils a negative prognostic role associated with metformin use specifically within the Atezolizumab plus Bevacizumab group.

Abstract Background Antenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks’ gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function. Methods Date-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122–125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection. Results Preterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR

Abstract Background Pathologists commonly employ the Ki67 immunohistochemistry labelling index (LI) when deciding appropriate therapeutic strategies for patients with breast cancer. However, despite several attempts at standardizing the Ki67 LI, inter-observer and inter-laboratory bias remain problematic. We developed a flow cytometric assay that employed tissue dissociation, enzymatic treatment and a gating process to analyse Ki67 in formalin-fixed paraffin-embedded (FFPE) breast cancer tissue. Results We demonstrated that mechanical homogenizations combined with thrombin treatment can be used to recover efficiently intact single-cell nuclei from FFPE breast cancer tissue. Ki67 in the recovered cell nuclei retained reactivity against the MIB-1 antibody, which has been widely used in clinical settings. Additionally, since the method did not alter the nucleoskeletal structure of tissues, the nuclei of cancer cells can be enriched in data analysis based on differences in size and complexity of nuclei of lymphocytes and normal mammary cells. In a clinical study using the developed protocol, Ki67 positivity was correlated with the Ki67 LI obtained by hot spot analysis by a pathologist in Japan (rho = 0.756, P

Background: Traditional tumor classifications have relied on cellular origin, pathological morphological features, gene expression profiles, and more recently, the tumor immune microenvironment. While these classifications provide valuable insights, incorporating physiological classifications focusing on liver metabolic functions may lead to new discoveries. Summary: We proposed to reclassify benign and malignant hepatocellular neoplasms based on their physiological functions such as albumin production, bile acid production, glycolysis, glycogenesis, and adipogenesis. We further demonstrated the homology between signal pathways activated by the differentiation program of the normal hepatobiliary cells and those activated by genetic abnormalities in tumors. Specifically, Wnt/β-catenin, RAS, NOTCH, and TGF-β signaling not only contribute to cell differentiation via activation of liver-enriched transcription factors but also determine the tumor traits. Examining the distinctions between hepatocellular carcinomas (HCCs) that maintain or lose metabolic functions can yield valuable insights into the drivers of biological malignancy and tumor plasticity. Key Messages: To confirm the homology between the differentiation programs of normal hepatobiliary cells, hepatocellular adenomas (HCA), and HCC we identify liver-specific functions such as catabolism and anabolism within tumors. HCCs and HCAs that have lost these metabolic functions exhibit characteristics such as dedifferentiation, resemblance to biliary cells, or increased glycolysis. Focusing on this underexplored area will likely stimulate active research into new tumor characteristics.

Abstract Background Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. Methods From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. Results Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). Conclusions This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE.

Abstract For accurate mitotic cell division, replicated chromatin must be assembled into chromosomes and faithfully segregated into daughter cells. While protein factors like condensin play key roles in this process, it is unclear how chromosome assembly proceeds as molecular events of nucleosomes in living cells and how condensins act on nucleosomes to organize chromosomes. To approach these questions, we investigate nucleosome behavior during mitosis of living human cells using single-nucleosome tracking, combined with rapid-protein depletion technology and computational modeling. Our results show that local nucleosome motion becomes increasingly constrained during mitotic chromosome assembly, which is functionally distinct from condensed apoptotic chromatin. Condensins act as molecular crosslinkers, locally constraining nucleosomes to organize chromosomes. Additionally, nucleosome-nucleosome interactions via histone tails constrain and compact whole chromosomes. Our findings elucidate the physical nature of the chromosome assembly process during mitosis.

Abstract Background Predicting the origin of premature ventricular contraction (PVC) from the preoperative electrocardiogram (ECG) is important for catheter ablation therapies. We propose an explainable method that localizes PVC origin based on the semantic segmentation result of a 12‐lead ECG using a deep neural network, considering suitable diagnosis support for clinical application. Methods The deep learning‐based semantic segmentation model was trained using 265 12‐lead ECG recordings from 84 patients with frequent PVCs. The model classified each ECG sampling time into four categories: background (BG), sinus rhythm (SR), PVC originating from the left ventricular outflow tract (PVC‐L), and PVC originating from the right ventricular outflow tract (PVC‐R). Based on the ECG segmentation results, a rule‐based algorithm classified ECG recordings into three categories: PVC‐L, PVC‐R, as well as Neutral, which is a group for the recordings requiring the physician's careful assessment before separating them into PVC‐L and PVC‐R. The proposed method was evaluated with a public dataset which was used in previous research. Results The evaluation of the proposed method achieved neutral rate, accuracy, sensitivity, specificity, F1‐score, and area under the curve of 0.098, 0.932, 0.963, 0.882, 0.945, and 0.852 on a private dataset, and 0.284, 0.916, 0.912, 0.930, 0.943, and 0.848 on a public dataset, respectively. These quantitative results indicated that the proposed method outperformed almost all previous studies, although a significant number of recordings resulted in requiring the physician's assessment. Conclusions The feasibility of explainable localization of premature ventricular contraction was demonstrated using deep learning‐based semantic segmentation of 12‐lead ECG. Clinical trial registration: M26‐148‐8.

Introduction: There have been few reports of patients for whom a cancer gene panel test for solid tumors revealed the simultaneous presence of BRCA mutation and microsatellite instability (MSI)-high status. BRCA mutations have been reported in 13% of castration-resistant prostate cancer (CRPC) patients, and 3.1% of prostate cancer cases are MSI-high/mismatch repair deficient. Case Presentation: A 71-year-old man with a history of urinary retention was referred to our department for clinically suspected prostate cancer and a high prostate-specific antigen (PSA) level (141 ng/mL). MRI revealed features of prostate cancer invading the bladder, seminal vesicles, and rectum. A histopathological examination of a transperineal needle biopsy specimen obtained from the prostate revealed adenocarcinoma. Bone scintigraphy revealed multiple metastases. The patient was treated with abiraterone acetate combined with androgen deprivation therapy followed by local radiation. Rectal wall thickening and lymph node metastasis were also observed, and docetaxel was administered. A cancer gene panel test was positive results for BRCA2 mutation with a MSI-high. After six courses of docetaxel, lymph node enlargement was observed and olaparib was initiated. Two months later, the metastatic lesions showed enlargement and the PSA level increased. Subsequently, pembrolizumab was administered. At 2 to the patient months after the initiation of pembrolizumab administration, PSA levels decreased to

Video Assistant Referee (VAR) is used for line judging in tennis to improve the fairness of a game. However, currently, popular VAR systems are based on three-dimensional trajectories and do not take actual ball bounce marks into account, which may lead to misjudgment due to misalignment. Therefore, in this paper, we propose Apollon Mark, a bounce mark visualization system with preceding mirror control based on high-speed drop location prediction. Based on high-speed measurement of three-dimensional position and motion prediction, the proposed system enables a high-resolution camera to capture the ground texture both before and after the ball drops on the ground by directing the angle of view of the camera to the predicted drop location of the ball before it drops. The system then enables bounce mark visualization by simple differential processing between the before and after images with a template-matching image processing algorithm. We have quantitatively evaluated the validity of the proposed system through the simulation of drop location prediction for real-scale tennis ball trajectories and validated the bounce mark visualization algorithm under a dynamic angle of view using galvanometer mirrors.

This study aimed to evaluate the associations of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels at

Introduction: Postoperative spinal epidural hematoma (PSEH) is a severe complication of spinal surgery that necessitates accurate and timely diagnosis. This study aimed to assess the accuracy of ultrasonography as an alternative diagnostic tool for PSEH after microendoscopic laminotomy (MEL) for lumbar spinal stenosis, comparing it with magnetic resonance imaging (MRI). Methods: A total of 65 patients who underwent MEL were evaluated using both ultrasound- and MRI-based classifications for PSEH. Intra- and interrater reliabilities were analyzed. Furthermore, ethical standards were strictly followed, with spine surgeons certified by the Japanese Orthopaedic Association performing evaluations. Results: Among the 65 patients, 91 vertebral segments were assessed. The intra- and interrater agreements for PSEH classification were almost perfect for both ultrasound (κ=0.824 [95% confidence interval (CI) 0.729-0.918] and κ=0.810 [95% CI 0.712-0.909], respectively) and MRI (κ=0.839 [95% CI 0.748-0.931] and κ=0.853 [95% CI 0.764-0.942], respectively). The results showed high concordance between ultrasound- and MRI-based classifications, validating the reliability of ultrasound in postoperative PSEH evaluation. Conclusions: This study presents a significant advancement by introducing ultrasound as a precise and practical alternative to MRI for PSEH evaluation. The comparable accuracy of ultrasound to MRI, rapid bedside assessments, and radiation-free nature make it valuable for routine postoperative evaluations. Despite the limitations related to specific surgical contexts and clinical outcome assessment, the clinical potential of ultrasound is evident. It offers clinicians a faster, cost-effective, and repeatable diagnostic option, potentially enhancing patient care. This study establishes the utility of ultrasound in evaluating postoperative spinal epidural hematomas after MEL. With high concordance to MRI, ultrasound emerges as a reliable, practical, and innovative tool, promising improved diagnostic efficiency and patient outcomes. Further studies should explore its clinical impact across diverse surgical scenarios.

Introduction: We aimed to implement the enhanced recovery after surgery (ERAS) protocol for pediatric neuromuscular scoliosis (NMS) surgery and to examine the effectiveness of this program in this study. Methods: Subjects were children with NMS who underwent scoliosis surgery at our department by a surgeon using a single posterior approach. A series of 27 cases before the introduction of ERAS and 27 cases during program stabilization were included in the study. Patient backgrounds did not show significant differences before and after introducing ERAS. Perioperative data, complications, length of hospital stay (LOS), and readmission within 90 days were investigated and statistically analyzed. Results: When the pre- and post-ERAS induction groups were compared, no significant differences in anesthesia induction time (p=0.979), pelvic fixation (p=0.586), fusion levels (p=0.479), intraoperative hypothermia duration (p=0.154), end-of-surgery body temperature (p=0.197), operative time (p=0.18), postoperative main Cobb angle (p=0.959), main Cobb angle correction rate (p=0.91), postoperative spino-pelvic obliquity (SPO) (p=0.849), and SPO correction rate (p=0.267) were observed. However, significant differences in using V-flap technique (p=0.041), intraoperative blood loss (p=0.001), and LOS (p=0.001) were observed. Intraoperative blood loss was weakly correlated with LOS (p=0.432 and 0.001). No statistically significant difference existed between the V-flap method and LOS (p=0.265). Multiple regression analysis using LOS as the objective variable and ERAS protocols and intraoperative blood loss as explanatory variables revealed that the effect of ERAS on LOS was greater than that of intraoperative blood loss. No statistically significant differences in the readmission rates within 90 days were found. Conclusions: After the introduction of ERAS, LOS decreased without an increase in complications or readmissions within 90 days.

Abstract Images collected during NASA’s Double Asteroid Redirection Test (DART) mission provide the first resolved views of the Didymos binary asteroid system. These images reveal that the primary asteroid, Didymos, is flattened and has plausible undulations along its equatorial perimeter. At high elevations, its surface is rough and contains large boulders and craters; at low elevations its surface is smooth and possesses fewer large boulders and craters. Didymos’ moon, Dimorphos, possesses an intimate mixture of boulders, several asteroid-wide lineaments, and a handful of craters. The surfaces of both asteroids include boulders that are large relative to their host body, suggesting that both asteroids are rubble piles. Based on these observations, our models indicate that Didymos has a surface cohesion ≤ 1 Pa and an interior cohesion of ∼10 Pa, while Dimorphos has a surface cohesion of

Abstract An earthquake with a moment magnitude of 7.5 (Mw) struck the northern Noto Peninsula, Ishikawa Prefecture, Japan, at 16:10 local time on January 1, 2024. This earthquake triggered a tsunami that propagated along the coastline of Ishikawa, Toyama, and Niigata Prefectures facing the Sea of Japan and significantly damaged coastal communities and infrastructure. Approximately 70 researchers from 23 universities or other institutes throughout Japan formed a joint research group to conduct a post-tsunami survey along a 340 km stretch of the coast. Based on the watermarks and traces of the tsunami, the inundation and run-up heights were surveyed using total stations, automatic optical levels, laser range finders, and a real-time kinematic (RTK) Global Navigation Satellite System (GNSS). The tidal correction was adjusted using astronomical tidal tables. In total, 303 survey records have been compiled, generating the NP2024TS (Noto Peninsula 2024 Tsunami Survey) dataset. This dataset provides comprehensive information on the inundation and run-up heights of the tsunami, which is useful for understanding tsunami characteristics and validating numerical tsunami models.

Abstract Purpose This study analyzed the efficacy of web excision combined with a pre-membranous incision on the dilated proximal segment for congenital intestinal atresia with type I and stenosis (CIA-I/S). Patients and methods Twenty-six patients underwent surgery for CIA-I/S from January 1990 to June 2022. Patients were categorized into 3 groups according to the surgical procedure: Group A, web excision with pre-membranous incision of the dilated intestine (n = 14); Group B, enteroplasty with a trans-membranous vertical incision (n = 7) and Group C, diamond-shaped anastomosis (n = 5). To minimize the impact of obstruction location on outcomes, we specifically examined 17 cases of duodenal atresia/stenosis: Group D-A, (n = 6); Group D-B, (n = 6) and Group D-C, (n = 5). We retrospectively compared the operative and postoperative parameters among the three groups. Results No patient experienced anastomotic leakage or obstruction. There were no significant differences in operative duration or blood loss among the 3 Groups. The median time to feeding initiation was 4, 6.5, and 5 days in Groups A, B, and C, respectively (p = 0.04) and was 4, 6.5, and 5 days in Groups D-A, D-B, and D-C, respectively (p = 0.04). Conclusion Web excision, when compared to enteroplasty and diamond-shaped anastomosis, showed comparable results in terms of the operative duration and postoperative complications. However, it may allow for an earlier initiation of enteral nutrition.

Abstract Objectives The objective of this study is to identify the effect of cribriform pattern 4 carcinoma/intraductal carcinoma of the prostate (CC/IDCP) on persistent prostate‐specific antigen (PSA) levels after robot‐assisted radical prostatectomy (RARP) in patients with localized prostate cancer (PCa). Patients and Methods This retrospective study included 730 consecutive patients with localized PCa who underwent RARP at Mie University (n = 392) and Aichi Medical University (n = 338) between 2015 and 2021. Patients with clinically metastatic PCa (cN1 and cM1) and those who received neoadjuvant and/or adjuvant therapy before biochemical recurrence were excluded. We evaluated the effects of CC/IDCP on persistent PSA levels after RARP. Persistent PSA was defined as PSA level ≥0.2 ng/mL at 1 month postoperatively and consecutively thereafter. Using factors from logistic regression analysis, models were developed to predict persistent PSA levels. Results Approximately 6.3% (n = 46) of the patients had persistent PSA levels. Patients with biopsy CC/IDCP (bCC/IDCP) and pathological CC/IDCP (pCC/IDCP) based on RARP specimens were 11.6% (85/730) and 36.5% (267/730), respectively. Multivariate analysis of the prediction of persistent PSA levels using preoperative factors revealed that PSA density, percentage of positive cancer cores, biopsy grade group and bCC/IDCP were independent prognostic factors. Furthermore, multivariate analysis of the prediction of persistent PSA levels using postoperative factors, excluding pN1, revealed that pathological grade group, pCC/IDCP, seminal vesicle invasion and lymphovascular invasion were independent prognostic factors. In the receiver operating characteristic curve analysis for predicting persistent PSA after RARP, areas under the receiver operating characteristic curve for the model with preoperative factors, postoperative factors, including pN1, and postoperative factors, excluding pN1, were 0.827, 0.833 and 0.834, respectively. Conclusions bCC/IDCP predicted persistent PSA after RARP in the overall population, while pCC/IDCP predicted persistent PSA only when the pN1 population was excluded. This may be useful for predicting susceptible patients with worse outcomes.

Abstract Osteoporosis, vertebral fractures, and spinal degenerative diseases are common conditions that often coexist in older adults. This study aimed to determine the factors influencing low back pain and its impact on activities of daily living (ADL) and physical performance in older individuals with multiple comorbidities. This cross-sectional study was part of a large-scale population-based cohort study in Japan, involving 1009 participants who underwent spinal magnetic resonance imaging (MRI) to assess cervical cord compression, radiographic lumbar spinal stenosis, and lumbar disc degeneration. Vertebral fractures in the thoracolumbar spine were evaluated using sagittal MRI with a semi-quantitative method. Bone mineral density was measured using dual-energy X-ray absorptiometry. Low back pain, Oswestry Disability Index (ODI), and physical performance tests, such as one-leg standing time, five times chair-stand time, maximum walking speed, and maximum step length, were assessed. Using clinical conditions as objective variables and image evaluation parameters as explanatory variables, multiple regression analysis showed that vertebral fractures were significantly associated with low back pain and ODI. Vertebral fractures and osteoporosis significantly impacted physical performance, whereas osteoporosis alone did not affect low back pain or ODI. Our findings contribute to new insights into low back pain and its impact on ADL and physical performance.

Abstract Introduction Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis that greatly impacts functioning and quality of life and can be difficult to treat. Approved treatment options for PPP are limited, and many patients do not fully respond to current treatments. Methods This was a randomized, double-blind, placebo-controlled, phase 2 study in Japanese patients with moderate to severe PPP and inadequate response to topical treatment. Patients were randomized 1:1 to receive apremilast 30 mg twice daily or placebo for 16 weeks followed by an extension phase where all patients received apremilast through week 32. PPP Area and Severity Index (PPPASI), modified PPPASI (which evaluates pustules and vesicles separately), and Palmoplantar Severity Index (PPSI) total scores and subscores (erythema, pustules/vesicles, and desquamation/scales) were evaluated over 32 weeks of apremilast treatment. Achievement of ≥ 50% improvement in PPPASI (PPPASI-50) was evaluated at week 16 among baseline demographic and clinical characteristic subgroups. Results At week 16, improvements in total score and subscores for PPPASI, modified PPASI, and PPSI, as well as rates of PPPASI-50 were at least moderately greater with apremilast than placebo. Mean PPPASI total score decreased by − 68.3% from baseline to week 32 with continued apremilast treatment. At week 32, mean change from baseline in PPPASI/modified PPPASI subscores ranged from − 58.5% to − 77.0% with apremilast. At week 32, PPSI total score for physician and patient assessments decreased by − 51.3% and − 40.0%, respectively, with continued apremilast treatment. PPPASI-50 response at week 16 was greater with apremilast versus placebo in most demographic and baseline characteristic subgroups. Conclusions Improvements in all PPPASI and PPSI total scores and subscores observed with apremilast over 16 weeks were maintained through 32 weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Rates of PPPASI-50 response at week 16 were mostly consistent across patient subgroups. ClinicalTrials.gov NCT04057937.

Study Design Retrospective single-center study. Purpose This study aimed to examine the factors associated with the self-image domain of the Scoliosis Research Society-22 revised (SRS-22r) in patients who underwent corrective surgery for adult idiopathic scoliosis (AdIS). Overview of Literature Adult spinal deformity (ASD) can be classified into AdIS and de novo scoliosis. However, no studies have investigated the effect of different ASD pathologies on self-image. Methods This study enrolled 60 patients who underwent corrective surgery and were followed up for >2 years postoperatively. AdIS was defined as adolescent idiopathic scoliosis in patients who had no history of corrective surgery, had a primary thoracolumbar/lumbar (TL/L) curve, and were ≥30 years old at the time of surgery. Results The AdIS (n=23; mean age, 53.1 years) and de novo (n=37; mean age, 70.0 years) groups were significantly different in terms of the main thoracic and TL/L curves, sagittal vertical axis, thoracic kyphosis, and thoracolumbar kyphosis preoperatively. The scores in the self-image domain of the SRS-22r (before surgery/2 years after surgery [PO2Y]) were 2.2/4.4 and 2.3/3.7 in the AdIS and de novo groups, respectively, and PO2Y was significantly different between the two groups (p

Polycrystalline diamond compact (PDC) bits, which are widely used in oil and gas well drilling, have begun to be used in geothermal well drilling. Mitsubishi Materials Corporation, K. Maikai Co., Ltd, and National Institute of Advanced Industrial Science and Technology started collaborative research project commissioned by Japan Organization for Metals and Energy Security with the aim of development of PDC bits that have satisfying efficiency to drill hard, inhomogeneous and fractured formations as is common in the geothermal fields. In the present report, the outline of the project is provided, including the development of PDC cutters and bits and the performance evaluation of PDC bits through laboratory and field drilling tests. Three predetermined numerical goals concerning the drilling performance, namely drilling speed, bit life, and gage loss, were achieved in the project. The ROP model proposed by Miyazaki et al. (2022), which was constructed based on a series of laboratory drilling tests under controlled conditions conducted as part of the project, is also reviewed. The model considers the effect of bit wear quantitatively and has an extremely simple form compared with earlier models. The applicability of the model to field drilling data and several future issues are also discussed.

Abstract We examine neutrino zeromode solutions on the electroweak Z-string and their effect on the stability of the string in the standard model and its extensions. We propose using topological invariants constructed from the momentum (and real) space topology of Green’s functions, often used for investigating edge modes in condensed matter physics. We analyze the standard model and then examine type-I and type-II extensions of the neutrino sector as well as their hybrid. Based on this analysis, we also comment on proposals in the literature to stabilize the Z-string.

ABSTRACT Aims This study aimed to investigate the association of maternal birth weight (MBW) with early and late gestational diabetes mellitus (GDM). Methods A total of 69318 pregnant Japanese women were included in this birth cohort study. The associations between maternal birth weight and early gestational diabetes mellitus (diagnosed at

Good syndrome (GS) is a combined immunodeficiency that is associated with thymomas. The cause of the reduction in B-cells in patients with GS may be multifactorial and may include dysregulated T-cell responses. It has been proposed that tumorigenesis in a normal thymus alters thymic epithelial cell function, which leads to attenuated elimination of T-cells autoreactive to B-cells. Although the comprehensive genetic analysis of thymoma has been performed and reported in many articles, the comprehensive genetic analysis specified for GS-related thymoma has not been reported. Herein, we report comprehensive genetic analysis of a thymoma taken from a patient with GS. Oncogenesis-associated genes that may contribute to thymoma development were detected. Additionally, alteration of VCAM1, which is required in the interaction between T-cells and thymic epithelial cells, was observed. Aberrantly expressed VCAM1 in thymic epithelial cells may decrease the efficacy of negative of selection autoreactive T-cells and contribute to autoimmunity to B-cells.

Abstract Introduction Psoriasis involvement in special areas (e.g., scalp or nails) is associated with a great disease burden yet it is often inadequately treated with topical treatments. The efficacy and tolerability of apremilast plus existing topical therapy in Japanese patients with mild to moderate plaque psoriasis were demonstrated in PROMINENT, a phase 3b, multicenter, open-label, single-arm study. We evaluated the efficacy of apremilast across disease severities and special areas involved in these patients. Methods In PROMINENT, patients received apremilast 30 mg twice daily for 16 weeks in addition to their existing topical therapy, with the option of topical therapy reduction at the discretion of their physician while continuing apremilast treatment from Weeks 16 to 32. We performed a post hoc analysis, assessing apremilast efficacy and safety in Japanese patients stratified by baseline static Physician Global Assessment (sPGA) score (2 [mild] or 3 [moderate]) and special area involvement. Results Of patients with baseline sPGA = 2 and sPGA = 3, 62.7% and 30.7%, respectively, achieved sPGA score 0 or 1 at Week 32. At Week 32, improvements in skin, nail, scalp, and quality of life assessments were observed regardless of baseline sPGA score. Improvements in these endpoints at Week 32 were also observed in patients with special area (scalp or nail) involvement (n = 134). Incidence of adverse events was similar between patients with baseline sPGA = 2 and sPGA = 3. Conclusions Apremilast in combination with topical therapy may be a beneficial treatment for Japanese patients, who have limited systemic treatment options for mild to moderate psoriasis or psoriasis in special areas. Trial Registration NCT03930186.

Abstract Background Ipilimumab (Ipi) plus nivolumab (Nivo) is the recommended first-line treatment for renal cell carcinoma (RCC). This report describes a case where pancreatic metastases disappeared after only two courses of Ipi + Nivo therapy. The primary tumor was cured by surgery, and a pathological Complete Response (pCR) was observed despite multiple serious immune-related Adverse Events (irAEs). Case presentation A 54-year-old woman with RCC and pancreatic metastasis at stage IV, diagnosed with intermediate risk according to the International Metastatic RCC Database Consortium classification, underwent initiation of Ipi + Nivo therapy. On day 26, she developed hyperthyroidism accompanied by tachycardia, leading to the commencement of metoprolol tartrate treatment. Following the resolution of tachycardia, a second course of Ipi + Nivo therapy was administered on day 50. By day 70, the patient exhibited Grade 3 hepatic dysfunction, followed by the onset of hypothyroidism on day 75, necessitating treatment with steroids and levothyroxine. After positive treatment, a Grade 3 skin disorder emerged on day 87 while tapering steroids, prompting treatment with methylprednisolone (mPSL) pulse therapy. The skin disorder responded to steroids, allowing for tapering. However, on day 113, a recurrence of Grade 3 skin disorder occurred, necessitating another mPSL pulse. The patient responded well to treatment, exhibiting improvement in her condition. On day 131, she presented at the hospital with complaints of respiratory distress, prompting a Computed Tomography (CT) scan that revealed interstitial pneumonia. By day 272, subsequent CT imaging showed the disappearance of pancreatic metastasis and shrinkage of the primary tumor. On day 294, she underwent a laparoscopic left nephrectomy. Pathological analysis confirmed a pCR in the primary tumor, indicating successful eradication of RCC through surgical intervention. Conclusions This case report presents a scenario where multiple severe irAEs appeared in a patient, yet metastases disappeared after only two courses of Ipi + Nivo therapy. The patient was ultimately cured by surgery and achieved a pCR. This case highlights that despite the occurrence of severe irAEs during RCC treatment with Ipi + Nivo therapy, they can be managed appropriately to maximize the therapeutic effects of checkpoint inhibitors.

Abstract Gradient Flow Exact Renormalization Group (GF-ERG) is a framework to define the renormalization group flow of Wilsonian effective action utilizing coarse-graining along the diffusion equations. We apply it for Scalar Quantum Electrodynamics and derive flow equations for the Wilsonian effective action with the perturbative expansion in the gauge coupling. We focus on the quantum corrections to the correlation functions up to the second order of the gauge coupling and discuss the gauge invariance of the GF-ERG flow. We demonstrate that the anomalous dimension of the gauge field agrees with the standard perturbative computation and that the mass of the photon keeps vanishing in general spacetime dimensions. The latter is a noteworthy fact that contrasts with the conventional Exact Renormalization Group formalism in which an artificial photon mass proportional to a cutoff scale is induced. Our results imply that the GF-ERG can give a gauge-invariant renormalization group flow in a non-perturbative way.

Abstract Background Global studies exploring the relationship between parity and chronic kidney disease (CKD) are scarce. Furthermore, no study has examined the relationship between parity and CKD in Japan. Therefore, this study aimed to examine the relationship between parity and the prevalence of CKD in a Japanese population, considering the clinical history of hypertensive disorders of pregnancy (HDP) and current body mass index (BMI) based on menopausal status. Methods This cross-sectional study included 26,945 Japanese multiparous women (5,006 premenopausal and 21,939 postmenopausal women) and 3,247 nulliparous women (1,599 premenopausal and 1,648 postmenopausal women). Participants were divided into two groups based on their menopausal status (premenopausal and postmenopausal women). The relationship between parity and the prevalence of CKD was evaluated using a multiple logistic regression model adjusted for several covariates, including a clinical history of HDP and current BMI. Results The relationship between parity and the prevalence of CKD was not statistically significant in either premenopausal or postmenopausal multiparous women. A clinical history of HDP was significantly associated with an increased risk of CKD in premenopausal and postmenopausal multiparous women. However, the relationship between a clinical history of HDP and CKD in premenopausal women was weakened after adjusting for current BMI. Furthermore, the current BMI was significantly associated with an increased risk of CKD in both premenopausal and postmenopausal women. Conclusions Parity is not significantly associated with the prevalence of CKD in premenopausal and postmenopausal multiparous women. A clinical history of HDP is a risk factor for CKD in both premenopausal and postmenopausal women. Current BMI is also associated with an increased risk of CKD in premenopausal and postmenopausal women. Therefore, continuous surveillance and preventive measures against CKD should be provided to women with a clinical history of HDP. In addition, maintaining an appropriate body weight is beneficial in reducing the risk of CKD.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic has changed our lifestyle by imposing restrictions, such as physical distancing. The effect of COVID-19 prevalence on seasonal variations in glycemic control in patients with diabetes mellitus (DM) remains unknown. Methods This single-center retrospective cohort study evaluated glycemic control in patients with type 2 DM who visited Sugi Cardiovascular Hospital in December 2021. We evaluated the clinical findings of all patients treated regularly between March 1, 2019, and December 31, 2021, including the periods both before and after the COVID-19 pandemic. All the standard treatments were approved. Furthermore, seasonal changes in hemoglobin A1c (HbA1c) levels were evaluated using stratified analyses based on age. Results This study analyzed 86 patients (mean age, 69.6 ± 9.2 years; men, 57). Median HbA1c (National Glycohemoglobin Standardization Program [Union of Clinical Chemistry]) levels in spring (March) were 7.70% (interquartile range (IQR):7.23%–8.30%) [60.6 mmol/mol (IQR:55.4–67.2 mmol/mol)], 7.35% (IQR:6.90%–7.90%) [56.8 mmol/mol (IQR:51.9–62.8 mmol/mol)], and 7.50% (IQR:7.10%–8.00%) [58.5 mmol/mol (IQR:54.1–63.9 mmol/mol)] in 2019, 2020, and 2021, respectively. During these periods, HbA1c levels and body mass index (BMI) revealed significant seasonal variations “high in spring” and “low in autumn.” Median HbA1c levels in spring (March) and autumn (September) were 7.86% [61.2 mmol/mol] and 7.48% [57.4 mmol/mol] in 2019 (P

Objectives: In the present study, we performed a detailed analysis of deglutitive dynamics during sleep in patients with obstructive sleep apnea (OSA) using a methodology developed by Sato et al. We hypothesized that the frequency of deglutition would decrease with increasing severity of OSA. The aim of this study is to clarify the involvement of deglutitive dynamics during sleep in OSA by investigating the correlations between deglutition and sleep parameters. Methods: This study included 30 adult patients with OSA. To analyze deglutition dynamics during sleep, surface electromyography recordings of the suprahyoid and thyrohyoid neck muscles, which are involved in deglutition, were performed simultaneous with conventional polysomnography. The “index of deglutition” was defined as the frequency of deglutition per hour of sleep. We examined correlations between this index and sleep parameters (apnea-hypopnea index [AHI], apnea index, hypopnea index, and lowest blood oxygen saturation). Results: By analyzing the obtained polysomnography and electromyography waveforms, we identified two deglutition patterns with and without respiratory arousal during sleep. We found a significant negative correlation between the index of deglutition in sleep stage 1 and the AHI, with a correlation coefficient of –0.48. (p=0.02) Conclusions: In the current study, we distinguished deglutition during sleep with and without arousal. In addition we discovered a significant negative correlation between the index of deglutition in sleep stage 1 and the AHI. This new finding will provide a platform for future research on OSA in aspiration pneumonia.

Objectives: The aim of this study was to evaluate the safety and efficacy of microdebrider adenoidectomy on sleep-disordered breathing among pediatric patients with OSA. Methods: In the microdebrider group (Group I), there were 30 Japanese OSA patients consisting of 26 boys and 4 girls. For comparison, we had 15 children (13 boys and 2 girls) who underwent classical adenoidectomy (Group II). Patients in Group I were selected from a pool of 95 pediatric Japanese OSA patients and were matched by age, preoperative AHI, and Kaup index with those in Group II. Parameters such as the amount of residual adenoid tissue, bleeding, duration of the procedure, and sleep-related metrics were compared between the two groups. Results: A significant improvement in postoperative AHI was observed in Group I (p

Objective: To determine whether the combination of the pharyngeal tonsil grade and palatine tonsil grade results in differences in the apnea–hypopnea index (AHI) and to determine whether each parameter separately (pharyngeal tonsil grade and palatine tonsil grade) results in differences in severe obstructive sleep apnea (OSA). Methods: This cross-sectional study involved 107 children (mean age, 7.2 years; range, 4–12 years) suspected of having OSA because of snoring or sleep-related complaints. The patients underwent polysomnography, and their palatine and pharyngeal tonsils were graded. Results: In examining whether the palatine tonsils and pharyngeal tonsils could be risk factors for severe OSA, the adjusted odds ratios were 4.42 for palatine tonsil grade 4 versus 1–3 and 10.40 for pharyngeal tonsil grade 4 versus 1–3; both were highly statistically significant. We also found that the AHI when both the pharyngeal and palatine tonsils were grade 4 was higher than the AHI expected for the pharyngeal and palatine tonsils alone. Conclusions: The combination of grade 4 pharyngeal tonsils and grade 4 palatine tonsils resulted in an AHI much higher than the AHI of other combinations (pharyngeal tonsils grades 1–3 and 4, palatine tonsils grades 1–3 and 4). We believe that grade 4 pharyngeal tonsils and grade 4 palatine tonsils have a great influence on severe OSA and that grade 4 pharyngeal tonsils increase the AHI.

Abstract Duchenne muscular dystrophy (DMD) is an intractable X-linked muscular dystrophy caused by mutations in the DMD gene. While many animal models have been used to study the disease, translating findings to humans has been challenging. Microminipigs, with their pronounced physiological similarity to humans and notably compact size amongst pig models, could offer a more representative model for human diseases. Here, we accomplished precise DMD modification in microminipigs by co-injecting embryos with Cas9 protein and a single-guide RNA targeting exon 23 of DMD. The DMD-edited microminipigs exhibited pronounced clinical phenotypes, including perturbed locomotion and body-wide skeletal muscle weakness and atrophy, alongside augmented serum creatine kinase levels. Muscle weakness was observed as of one month of age, respiratory and cardiac dysfunctions emerged by the sixth month, and the maximum lifespan was 29.9 months. Histopathological evaluations confirmed dystrophin deficiency and pronounced dystrophic pathology in the skeletal and myocardial tissues, demonstrating that these animals are an unprecedented model for studying human DMD. The model stands as a distinct and crucial tool in biomedical research, offering deep understanding of disease progression and enhancing therapeutic assessments, with potential to influence forthcoming treatment approaches.

Abstract Background T-cell acute lymphoblastic leukemia (T-ALL) tends to involve central nervous system (CNS) infiltration at diagnosis. However, cases of residual CNS lesions detected at the end of induction and post early intensification have not been recorded in patients with T-ALL. Also, the ratio and prognosis of patients with residual intracranial lesions have not been defined. Case presentation A 9-year-old boy with T-ALL had multiple intracranial tumors, which were still detected post early intensification. To investigate residual CNS lesions, we used 11C-methionine (MET)-positron emission tomography. Negative MET uptake in CNS lesions and excellent MRD status in bone marrow allowed continuing therapies without hematopoietic cell transplantation. Conclusions In cases with residual lesions on imaging studies, treatment strategies should be considered by the systemic response, direct assessment of spinal fluid, along with further development of noninvasive imaging methods in CNS. Further retrospective or prospective studies are required to determine the prognosis and frequency of cases with residual intracranial lesions after induction therapy.

BackgroundThe addition of antiplatelet therapy to anticoagulant therapy in patients with stroke with non-valvular atrial fibrillation (NVAF) and atherothrombotic disease may increase bleeding risk without reducing recurrent stroke risk.AimsTo evaluate the clinical benefits of anticoagulant monotherapy compared to combination therapy with anticoagulants and antiplatelet agents.Methods and designThis is an investigator-initiated prospective multicenter, randomized, open-label, parallel-group clinical trial. Patients with NVAF and atherothrombotic disease who have had a recent ischemic stroke or transient ischemic attack will be eligible to participate in this trial.Study outcomesThe primary outcome is a composite of ischemic cardiovascular events, including cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization, and major bleeding events within 2 years after randomization.Sample size estimatesThis study will enroll 400 patients, 200 receiving anticoagulant monotherapy and 200 receiving combination therapy. This sample size will provide 90% power (one-sided p = 0.025) to detect a risk reduction in outcome events within 2 years, assuming event rates of 13 and 27% for each group, respectively, and a 10% loss to follow-up at a 2.5% significance level with one-sided log-rank tests at an interim analysis and a final analysis.DiscussionThis will be the first study to assess the net clinical benefit of oral anticoagulant monotherapy in ischemic stroke patients with NVAF and atherothrombosis.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT03062319, NCT03062319; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000029222, UMIN000025392; https://jrct.niph.go.jp/latest-detail/jRCTs051180202, jRCTs051180202.

IntroductionThe changing composition of non-cell autonomous circulating factors in blood as humans age is believed to play a role in muscle mass and strength loss. The mechanisms through which these circulating factors act in age-related skeletal muscle changes is not fully understood. In this study, we used human myogenic progenitors derived from human pluripotent stem cells to study non-cell autonomous roles of circulating factors during the process of myogenic differentiation.MethodsMyogenic progenitors from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) were supplemented with serum samples from aged or young Fischer 344 × Brown Norway F1-hybrid rats. The effect of aged or young serum supplementation on myogenic progenitor proliferation, myotube formation capacity, differentiation, and early transcriptomic profiles were analyzed.ResultsWe found that aged rat serum supplementation significantly reduced cell proliferation and increased cell death in both ESC- and iPSC-derived myogenic progenitors. Next, we found that the supplementation of aged rat serum inhibited myotube formation and maturation during terminal differentiation from progenitors to skeletal myocytes when compared to the cells treated with young adult rat serum. Lastly, we identified that gene expression profiles were affected following serum supplementation in culture.DiscussionTogether, aged serum supplementation caused cellular and transcriptomic changes in human myogenic progenitors. The current data from our in vitro model possibly simulate non-cell autonomous contributions of blood composition to age-related processes in human skeletal muscle.

Introduction Advances in treatment have transformed cancer from a fatal to a chronic illness. This requires healthcare professionals, particularly nurses, to have advanced knowledge and collaborative skills. However, challenges persist in implementing patient-centered care in the context of evolving treatment complexity. Objectives This study aimed to clarify nurses’ support practices in providing cancer pharmacotherapy at a university hospital in Japan and compare these practices based on nurses’ years of experience. Methods A questionnaire survey was conducted from February to April 2023 among 430 nurses involved in provision of cancer pharmacotherapy at a Japanese university hospital. Nurses were asked about the types of support they provided during care for patients undergoing cancer pharmacotherapy. Nurses’ cancer pharmacotherapy support practices were extracted using factor analysis, and differences in support scores by years of experience were examined. Results Responses were received from 184 nurses (42.8% response rate). Three support factors were identified: “Providing patient-centered cancer pharmacotherapy,” “Management of continued cancer pharmacotherapy treatment,” and “Assessment of and response to physical symptoms.” Scores for “Providing patient-centered cancer pharmacotherapy” were significantly lower than those for the other two factors ( p