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Abstract Direct functionalization of amino groups in complex organic molecules is one of the most important key technologies in modern organic synthesis, especially in the synthesis of bio-active chemicals and pharmaceuticals. Whereas numerous chemical reactions of amines have been developed to date, a selective, practical method for functionalizing complex amines is still highly demanded. Here we report the first late-stage N-alkylation of pharmaceutically relevant amines with alcohols at ambient temperature. This reaction was achieved by devising a mixed heterogeneous photocatalyst in situ prepared from Cu/TiO2 and Au/TiO2. The mixed photocatalytic system enabled the rapid N-alkylation of pharmaceutically relevant molecules, the selective mono- and di-alkylation of primary amines, and the non-symmetrical dialkylation of primary amines to hetero-substituted tertiary amines.

Cryogenic quantum computers play a leading role in demonstrating quantum advantage. Given the severe constraints on the cooling capacity in cryogenic environments, thermal design is crucial for the scalability of these computers. The sources of heat dissipation include passive inflow via intertemperature wires and the power consumption of components located in the cryostat, such as wire amplifiers and quantum–classical interfaces. Thus, a critical challenge is to reduce the number of wires by reducing the required intertemperature bandwidth while maintaining minimal additional power consumption in the cryostat. One solution to address this challenge is near-data processing using ultralow-power computational logic within the cryostat. Based on the workload analysis and domain-specific system design focused on variational quantum algorithms (VQAs), we propose the cryogenic counter-based coprocessor for VQAs (C3-VQA) to enhance the design scalability of cryogenic quantum computers under the thermal constraint. The C3-VQA utilizes single-flux-quantum logic, which is an ultralow-power superconducting digital circuit that operates at the 4 K environment. The C3-VQA precomputes a part of the expectation value calculations for VQAs and buffers intermediate values using simple bit operation units and counters in the cryostat, thereby reducing the required intertemperature bandwidth with small additional power consumption. Consequently, the C3-VQA reduces the number of wires, leading to a reduction in the total heat dissipation in the cryostat. Our evaluation shows that the C3-VQA reduces the total heat dissipation at the 4 K stage by 30% and 81% under sequential-shot and parallel-shot execution scenarios, respectively. Furthermore, a case study in quantum chemistry shows that the C3-VQA reduces total heat dissipation by 87% with a 10 000-qubit system.

Abstract Generalizability of AI colonoscopy algorithms is important for wider adoption in clinical practice. However, current techniques for evaluating performance on unseen data require expensive and time-intensive labels. We show that a "Masked Siamese Network" (MSN), trained to predict masked out regions of polyp images without labels, can predict the performance of Computer Aided Detection (CADe) of polyps on colonoscopies, without labels. This holds on Japanese colonoscopies even when MSN is only trained on Israeli colonoscopies, which differ in scoping hardware, endoscope software, screening guidelines, bowel preparation, patient demographics, and the use of techniques such as narrow-band imaging (NBI) and chromoendoscopy (CE). Since our technique uses neither colonoscopy-specific information nor labels, it has the potential to apply to more medical imaging domains.

Abstract Background The potential of carbon ion radiation therapy (CIRT) as a curative treatment for localized prostate cancer (PCa) has garnered attention due to its characteristic dose distribution. We prospectively collected and analyzed over five years to investigate the outcomes of localized PCa treated with CIRT at our institution. Patients and methods The study included patients with histologically confirmed prostate adenocarcinoma. CIRT treatment was administered at a total dose of 57.6 Gy (RBE) in 16 fractions over four weeks. Uroflowmetry (UFM) and residual urine measurements were performed at various time points: before CIRT treatment, one month after starting CIRT, three months after treatment, and annually for five years starting from 1 year after the completion of CIRT. Prostate volume was measured using transrectal ultrasonography (TRUS). Results A total of 304 prostate cancer patients were analyzed. UFM parameters were significantly worsened immediately after the treatment. However, they recovered to pretreatment levels after three months and remained stable until five years post-treatment. Notably, Average flow rate showed significant improvement after three years of treatment compared to before the treatment. Prostate volume decreased to 80% of baseline in patients treated with CIRT alone and to 60–70% of baseline in those receiving combined CIRT and either short- or long-term ADT. The logistic-binomial analysis identified post-voiding residual urine volume (PVR) as a significant factor for predicting adverse events in the acute phase. Conclusions Following CIRT treatment, the voiding parameters in PCa patients significantly deteriorated immediately. However, after three months, they returned to their pre-treatment levels and remained stable for five years.

An 11-year-old girl with quiescent ulcerative colitis had sustained elevation of liver enzymes. Although she had no clinical symptoms suggestive of Wilson’s disease, such as Kayser–Fleischer rings, laboratory data showed decreased serum copper and ceruloplasmin levels and increased urinary copper excretion. Genetic testing showed pathogenic variants in ATP7B allele 1: c.2004_2006delGAT (p. Met668del) and allele 2: c.1708-5T>G. After starting copper chelators, her liver function normalized, and she maintained clinical and endoscopic remission of ulcerative colitis. Mutations or defective functions of ATP7B lead to hepatic dysfunction and intestinal inflammation.

Summary: Background: The involvement of Mediterranean fever (MEFV) gene mutations in patients with inflammatory bowel disease unclassified (IBDU) remains unclear. This study aimed to determine the clinical characteristics and responsiveness to colchicine in Japanese patients with IBDU carrying MEFV mutations. Methods: In this retrospective cohort study, we examined MEFV mutations using gene analysis, clinical information, and colchicine responsiveness. Furthermore, we examined cytokine production in exon 2-mutated THP-1 cells (a monocytic cell line) and microbiome analysis. Findings: Of the 396 patients diagnosed with IBDU, 60.1% had MEFV mutations. Exon 2 mutations were the most common (83.7%). Among patients with available clinical information, 43.3% of patients with IBDU had typical Familial Mediterranean fever (FMF). The efficacy of colchicine in patients with IBDU carrying MEFV mutations was 84.6%. Significant differences were noted in the production of inflammatory; cytokines between THP-1 cells with and without MEFV mutations. Microbial compositions differed between patients with IBDU carrying MEFV mutations and patients with IBD and healthy controls. Interpretation: Patients with IBDU carrying MEFV mutations responded well to colchicine treatment. A notable subset of patients met the criteria for typical FMF. Alterations in intestinal microbiota may contribute to disease pathogenesis. Funding: This work was supported by the Japan Agency for Medical Research and Development (21ek0410057h0003), a grant from the Uehara Memorial Foundation, and the Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare (MHLW) of Japan (Investigation and Research for Intractable Inflammatory Bowel Disease; Grant Number 20316729).

Background: Patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) sometimes show unexpected liver, peritoneal, and para-aortic lymph node metastases intraoperatively. Despite radical pancreatectomy, a nonnegligible number of patients relapse within 6 months after surgery. The aim of this study was to identify the preoperative predictors of occult metastases (OM), defined as intraoperative distant metastases or within 6 months after pancreatectomy. Materials and methods: This study included patients with R and BR PDAC who underwent curative-intent pancreatectomy or staging laparoscopy between 2006 and 2021. Multivariate logistic regression and Cox hazard analyses were performed to identify the preoperative predictors of OM and to assess the impact of these factors on prognosis after pancreatectomy. Results: Of the 279 patients, OM was observed intraoperatively in 47 and postoperatively in 34. In the OM group, there were no differences in prognosis between patients who had intraoperative metastases and recurrence within 6 months (median survival time [MST], 18.1 vs. 12.9 months), and between patients who underwent pancreatectomy and those who did not (MST, 13.9 vs. 18.1 months). Preoperative tumor size ≥22 mm (odds ratio [OR], 2.03; 95 % confidence interval [CI], 1.16–3.53; p = 0.013) and preoperative CA19–9 level ≥ 118.8 U/mL (OR, 2.64; 95 % CI, 1.22–5.73; p = 0.014) were significant predictors of OM. Additionally, positive OM predictors were strong independent prognostic factors for overall survival after pancreatectomy (hazard ratio, 2.47; 95 % CI, 1.54–3.98; p

Japanese Mantispidae are revised, redescribed and illustrated with details of male and female terminalia. The following seven species are recognised: Austroclimaciella quadrituberculata (Westwood, 1852); Euclimacia badia Okamoto, 1910; Eumantispa harmandi (Navás, 1909); Tuberonotha strenua (Gerstaecker, 1894); Necyla shirozui (Nakahara, 1961); Mantispilla japonica (McLachlan, 1875); and M. transversa Stitz, 1913. In addition, we propose synonymising A. habutsuella (Okamoto, 1910) and A. subfusca (Nakahara, 1912) with A. quadrituberculata and M. j. diminuta Matsumura, 1907 with M. japonica.

Abstract Group 2 innate lymphoid cells (ILC2s) are a subset of innate lymphocytes that produce type 2 cytokines, including IL-4, IL-5, and IL-13. GATA3 is a critical transcription factor for ILC2 development at multiple stages. However, when and how GATA3 is induced to the levels required for ILC2 development remains unclear. Herein, we identify ILC2-specific GATA3-related tandem super-enhancers (G3SE) that induce high GATA3 in ILC2-committed precursors. G3SE-deficient mice exhibit ILC2 deficiency in the bone marrow, lung, liver, and small intestine with minimal impact on other ILC lineages or Th2 cells. Single-cell RNA-sequencing and subsequent flow cytometry analysis show that GATA3 induction mechanism, which is required for entering the ILC2 stage, is lost in IL-17RB+PD-1− late ILC2-committed precursor stage in G3SE-deficient mice. Cnot6l, part of the CCR4-NOT deadenylase complex, is a possible GATA3 target during ILC2 development. Our findings implicate a stage-specific regulatory mechanism for GATA3 expression during ILC2 development.

Objective: Imaging is essential for diagnosing large-vessel vasculitis (LVV). During diagnostic imaging, assessing disease activity and vascular damage separately is important. Acute-phase findings represent disease activity, while chronic-phase findings represent vascular damage; however, whether the imaging findings are acute or chronic may be unclear. We investigated how vascular lesions change before and after treatment and whether they were acute- or chronic-phase findings. Methods: Fifty-one patients with LVV who had undergone contrast-enhanced computed tomography (CT) scans from the neck to the pelvis before treatment and 1-4 months after treatment were recruited. Wall thickening, wall contrast enhancement, stenosis, occlusion, dilation, aneurysm, and calcification were semi-quantitatively assessed in 21 vessels from the common carotid to the common iliac artery. Results: Twenty-four patients were diagnosed with Takayasu arteritis (TAK), and 27 with giant cell arteritis (GCA). Wall thickening and wall contrast enhancement improved after the treatment, which was especially significant in the GCA group. No significant differences in stenosis, occlusion, dilation, aneurysm, or calcification were observed before and after treatment. Stenosis and occlusion were more common with TAK, while calcification was more common with GCA. Conclusion: Wall thickening and wall contrast enhancement are acute-phase findings (activity), while stenosis, occlusion, dilation, aneurysm, and calcification are chronic-phase findings (damage). The frequencies of these findings differ between TAK and GCA.

ObjectiveSeveral systematic reviews have shown that physical exercise positively affects motor function (MF) and quality of life (QoL) in patients with Parkinson's disease (PD). After the coronavirus disease (COVID-19) pandemic, numerous studies were conducted to reveal the effects of telerehabilitation for patients with PD. However, only a few empirical results of online programs for PD patients have been reported. Therefore, this study aimed to determine the effects of an online physical and cognitive training program on MF and QoL in patients with PD.MethodsWe evaluated the impact of our online program on the QoL and MF of patients with PD by comparing data at baseline and after six months of intervention. For the QoL assessment, we used the Schwab and England Activities of Daily Living scale and Parkinson's Disease Questionnaire (PDQ-39), whereas, for MF, we measured movement status using the modified 20-m walk test and timed up-and-go (TUG) test.ResultsWe enrolled 20 patients for QoL and 19 for MF in this study. For PDQ-39, social support (p = 0.046, δ = 0.320) and cognitions (p = 0.028, δ = 0.268) significantly improved. Additionally, cadence (p = 0.032, g = −0.377) in the modified 20-m walk and exam duration (p = 0.003, δ = 0.296) and forward gait (p = 0.003, δ = 0.341) in the TUG test showed significant differences before and after the intervention.ConclusionOur results suggest that online physical and cognitive training programs positively affect MF and QoL in individuals with PD.

Abstract Purpose To compare the clinical outcomes between opening wedge high tibial osteotomy (OWHTO) and unicompartmental knee arthroplasty (UKA) in patients with Ahlbäck Grade 3 medial compartmental knee osteoarthritis (OA) using a propensity score matching (PSM) analysis. Methods This retrospective study included all OWHTO and UKA procedures performed between 2016 and 2021 at a single institution. Inclusion criteria were patients diagnosed with medial knee OA, specifically Ahlbäck Grade 3 arthritis. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Radiographic parameters included hip–knee–ankle (HKA), medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA) and joint line convergence angle (JLCA). Primary outcomes included improvement in clinical scores at 3, 12 and 24 months post‐operatively. Secondary outcomes included radiographic parameters, complication rates and re‐intervention rates. One‐to‐one PSM was conducted based on gender, age and preoperative KOOS pain scores. Results After evaluating eligibility using PSM, a total of 50 knees in the UKA group and 50 knees in the OWHTO group were included. There was no significant difference between groups in preoperative overall KOOS, but the UKA group had better overall KOOS at 3 months (p

Abstract Purpose To compare clinical and radiological outcomes of medial opening wedge high tibial osteotomy (MOWHTO) using two different alignment methods: the alignment rod (AR) versus the gap measurement (GM) method. The primary outcome was to report the surgical accuracy of coronal plane corrections in each method. Methods Patients who underwent MOWHTO with either AR or GM method between 2014 and 2022 at a single institution, with a minimum of 2 years of follow‐up, were included. The opening gap was gradually spread with an AR under fluoroscopic control in the AR group, whereas the osteotomy site was opened to the value of the measured gap distance in addition to the thickness of the bone saw in the GM group. Radiological assessment of geometric characteristics included hip–knee–ankle angle (HKA), medial proximal tibial angle (MPTA), mechanical lateral distal femoral angle and joint line convergence angle. Surgical accuracy, which is the deviation (Δ) between the intended and achieved correction, was compared between both methods. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Scores. Results A total of 110 patients (n = 110 knees) with a mean age of 54.1 ± 8.4 years were included in the study. Radiological parameters were significantly improved as reflected by HKA correction from 171.6° ± 2.0° to 181.1° ± 2.6° in the AR group and from 171.0° ± 2.3° to 181.1° ± 2.8° in the GM group at 2 years (Intergroup n.s). There was no significant intergroup difference for all radiological parameters and clinical outcomes. There was no intergroup difference in the surgical accuracy as evaluated by Δvalues and absolute Δvalues of both HKA and MPTA (n.s). Conclusions Comparable correction accuracy was achieved in MOWHTO using either the AR or GM method. The GM method is simple and reliable in achieving the intended correction in MOWHTO. Level of Evidence Ⅲ retrospective comparative study.

In recent years, degenerative meniscal lesions have received increasing attention as an etiologic factor of knee osteoarthritis. Among various relevant factors, medial meniscal extrusion has been shown to be an independent predictor of the onset and progression of knee osteoarthritis. Therefore, surgical reduction of the extruded medial meniscus to restore meniscal function is key to preventing osteoarthritis of the knee. The arthroscopic centralization technique using knotless anchors has been developed and refined to reduce meniscal extrusion in the posteromedial region of the knee. Although a short-term study has reported favorable outcomes, the technique presents some pitfalls and can be technically challenging. This article describes the rationale and procedure for arthroscopic belt capsulodesis using 2 knotless anchors for reduction of medial meniscal extrusion. The reported procedure is technically simple and efficiently reduces meniscal extrusion by repairing the meniscotibial capsule, and it may be useful in the prevention of osteoarthritic progression.

Introduction Hand, foot, and mouth disease generally occurs in children. In rare cases, hand, foot, and mouth disease affects the testicles. Case presentation A 29‐year‐old man presented to our emergency department with testicular pain for several days after the onset of hand, foot, and mouth disease. Ultrasonography revealed hypoechoic mass‐like areas in the right testis. A mild inflammatory response was noted, tumor markers and urinary data were normal, and tests for infection were all negative. Antibiotics were initiated and ultrasonography was performed in every subsequent examination. Testicular pain disappeared 6 months later. Conclusion We encountered a rare case of a testicular lesion related to hand, foot, and mouth disease that was successfully treated. The careful selection of treatment for testicular pain and scrotal enlargement in young adult males, such as surgery and symptomatic treatment, based on their medical history and laboratory findings, is important.

Introduction Nontraumatic biliary rupture and retroperitoneal biloma infrequently occur. Here, we report a case of retroperitoneal biloma due to spontaneous left hepatic duct perforation, which was difficult to differentiate from a perirenal abscess. Case presentation A 94‐year‐old female patient was hospitalized with symptoms of fatigue and right back pain that lasted for 5 days. Computed tomography revealed fluid accumulation in the retroperitoneum, and urinary extravasation and right perinephric abscess were suspected. Antimicrobial treatment and drainage with ureteral stents and urethral catheters demonstrated no symptom improvement. Ultrasound‐guided puncture of the abscess revealed the presence of bile. Pigtail catheter drainage improved symptoms and inflammatory response. After diagnosis, endoscopic retrograde cholangiopancreatography revealed bile leakage, and a bile duct stent was inserted. Conclusion Biloma can cause perirenal fluid accumulation, and they should be considered an origin of perirenal fluid accumulation when urinary tract lesions are excluded.

Abstract Fluoride glasses in the binary system ZrF4–BaF2 were prepared via mechanochemical treatment. The glass-forming region of the ZrF4–BaF2 system obtained using the mechanochemical method was wider than that obtained using the conventional melt-quenching method. The glass–ceramic 60ZrF4·40BaF2 (mol%) sample was obtained by heat treatment and shows a higher conductivity of 1.2 × 10–6 S cm−1 at 200 °C than the pristine glass. This study revealed that mechanochemical treatment was effective for the synthesis of fluoride glasses.

Abstract Background Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions. Methods SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112). Results SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components. Conclusion Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.

A wafer-bonded vertical-cavity surface-emitting laser (VCSEL) was demonstrated by surface-activated bonding (SAB) of a GaAs-based distributed Bragg reflector (DBR) on a Ge substrate. Current injection lasing was achieved at the 1380 nm band under continuous-wave operation with AlGaInAs-based multi-quantum wells and a buried tunnel junction for current and optical confinement. The thermal conductivity of the VCSELs bonded by SAB was superior to that of InP VCSELs owing to high heat dissipation of GaAs DBR. This bonding method is suitable for short-wavelength infrared VCSELs and various other applications, including sensing, data communication, and silicon photonics.

In homeostatic conditions, the basal progenitor cells of the esophagus differentiate into a stratified squamous epithelium. However, in the setting of acid exposure or inflammation, there is a marked failure of basal cell differentiation, leading to basal cell hyperplasia. We have previously shown that lysyl oxidase (LOX), a collagen crosslinking enzyme, is upregulated in the setting of allergic inflammation of the esophagus; however, its role beyond collagen crosslinking is unknown. Herein, we propose a non-canonical epithelial-specific role of LOX in the maintenance of epithelial homeostasis using 3D organoid and murine models. We performed quantitative reverse transcriptase PCR, Western blot, histologic analysis, and RNA sequencing on immortalized non-transformed human esophageal epithelial cells (EPC2-hTERT) with short-hairpin RNA (shRNA) targeting LOX mRNA in both monolayer and 3D organoid culture. A novel murine model with a tamoxifen-induced Lox knockout specific to the stratified epithelium (K5CreER; Loxfl/fl) was utilized to further define the role of epithelial LOX in vivo. We found that LOX knockdown decreased the proliferative capacity of the esophageal epithelial cells in monolayer culture, and dramatically reduced the organoid formation rate (OFR) in the shLOX organoids. LOX knockdown was associated with decreased expression of the differentiation markers filaggrin, loricrin, and involucrin, with RNA sequencing analysis revealing 1224 differentially expressed genes demonstrating downregulation of pathways involved in cell differentiation and epithelial development. Mice with Lox knockout in their stratified epithelium demonstrated increased basaloid content of their esophageal epithelium and decreased Ki-67 staining compared to the vehicle-treated mice, suggesting reduced differentiation and proliferation in the Lox-deficient epithelium in vivo. Our results demonstrate, both in vivo and in vitro, that LOX may regulate epithelial homeostasis in the esophagus through the modulation of epithelial proliferation and differentiation. Understanding the mechanisms of perturbation in epithelial proliferation and differentiation in an inflamed esophagus could lead to the development of novel treatments that could promote epithelial healing and restore homeostasis.

Objective: The human adrenal cortex comprises three functionally and structurally distinct layers that produce layer-specific steroid hormones. With aging, the human adrenal cortex undergoes functional and structural alteration or “adrenal aging”, leading to the unbalanced production of steroid hormones. Given the marked species differences in adrenal biology, the underlying mechanisms of human adrenal aging have not been sufficiently studied. This study was designed to elucidate the mechanisms linking the functional and structural alterations of the human adrenal cortex. Methods: We conducted single-cell RNA sequencing and spatial transcriptomics analysis of the aged human adrenal cortex. Results: The data of this study suggest that the layer-specific alterations of multiple signaling pathways underlie the abnormal layered structure and layer-specific changes in steroidogenic cells. We also highlighted that macrophages mediate age-related adrenocortical cell inflammation and senescence. Conclusions: This study is the first detailed analysis of the aged human adrenal cortex at single-cell resolution and helps to elucidate the mechanism of human adrenal aging, thereby leading to a better understanding of the pathophysiology of age-related disorders associated with adrenal aging.

Abstract In rice (Oryza sativa L.) production, dry direct seeding is one of the most essential technologies to reduce labor input and to increase net income. Field experiments were conducted in southwestern Japan in 2019 and 2020 to determine the effects of nitrogen (N) application rate and timing on grain yield, lodging, grain appearance, and protein content in dry direct broadcast seeded rice under different weather conditions. In 2019, plants had larger source ability using the normal solar radiation at the tillering stage, regardless of N application timings. Plants with applied N at the reproductive stage produced the highest grain yield and the highest percentage of undamaged grains under high air temperature condition during the early ripening stage. In 2020, plants did not have larger source ability due to the lower solar radiation at the tillering stage. Plants with applied N at the reproductive stage produced the highest grain yield but produced the highest percentage of green immature grains. These results mean that solar radiation at the tillering stage may be important for increasing grain yield and quality in dry direct broadcast seeded rice. Therefore, since plants grown under normal solar radiation condition at the tillering stage may have large source ability, more N application at the reproductive stage may be recommended to increase grain yield. In contrast, since plants grown under low solar radiation condition at the tillering stage may have small source ability, less N application at the reproductive stage may be recommended to decrease the occurrence of green immature grains.

Objectives: For occupational health staff, the health status of the worksite is an important matter, and a single index for presenting this health status is desired. We applied a stroke prediction model to employees of a Japanese non-iron metal company working at 10 worksites to present health status of the worksite. Methods: We applied a stroke prediction model of the Japan Public Health Center-based Prospective Study to 2,807 male employees without history of cardiovascular disease. We additionally applied models from the Japan Arteriosclerosis Longitudinal Study and from the Suita Study for validation. As the expected value for each employee at a worksite, we calculated the mean of employees’ predicted 10-year stroke risk for each worksite. To adjust difference in age distribution, the stroke risk of each worksite was age-adjusted using the direct method. The expected values were presented as the representative value of a worksite with the 95% confidence interval calculated using the bootstrap method. Logistic regression analysis was conducted to explore the reason why a worksite exhibits a high risk. We examined if partial regression coefficients of the worst worksite were affected by modifiable risk factors. Results: Three models predicted similar stroke risks for 10 worksites. Difference in the predicted stroke risk was observed among the worksites even after age-adjustment. Diabetes mellitus was found to affect partial regression coefficient of the worst worksite in any of three prediction models. Conclusion: The stroke prediction model was observed to be a comprehensive tool for presenting a worksite’s health status.

Abstract Background and Aim Recently, noninvasive fecal markers have been used as indicators of intestinal inflammation in patients with inflammatory bowel disease (IBD). We conducted a clinical validation study to measure fecal calprotectin (Cp), lactoferrin (Lf), and hemoglobin (Hb) levels using an all‐in‐one kit in patients with IBD and colorectal tumors and aimed to clarify the utility of these fecal markers. Methods In this study, 104 patients were analyzed, including 25 patients with ulcerative colitis (UC), 20 with Crohn's disease (CD), 48 with colorectal tumors, and 13 healthy controls (HC). Of the 48 patients with colorectal tumors, 14 had invasive cancer. We validated the utility of fecal Cp, Lf, and Hb levels by simultaneously measuring fecal markers in patients with IBD and colorectal tumors. Results Fecal Cp and Lf had almost equivalent abilities in detecting clinical remission in patients with UC; however, fecal Cp was slightly superior to Lf. Regarding colorectal tumors, fecal Cp and Lf levels tended to be higher in patients with adenomas and colorectal cancer than in HCs. Although fecal Hb alone had the best sensitivity and specificity for detecting colorectal cancer, it had relatively low sensitivity for detecting advanced neoplasms and colorectal cancer. Conclusion Fecal Cp and Lf can be used as almost equivalent biomarkers to assess the clinical activity in patients with UC. Fecal Hb is the most useful marker for screening colorectal cancer; however, adding fecal Cp and Lf may compensate for the low sensitivity of detecting for advanced colorectal tumors based on Hb alone.

Abstract Background Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia–dysplasia–carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. Case presentation A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia–dysplasia–carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. Conclusions Herein, we report the first case of PVca with PBM potentially caused by a “hyperplasia–dysplasia–carcinoma sequence” detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.

Abstract Objectives IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with an unknown etiology, affecting single/multiple organ(s). Pathological findings include the infiltration of IgG4-producing plasma cells, obliterative phlebitis, and storiform fibrosis. Although immunological studies have shed light on the dysregulation of lymphocytes in IgG4-RD pathogenesis, the role of non-immune cells remains unclear. This study aimed to investigate the demographics and characteristics of non-immune cells in IgG4-RD and explore potential biomarkers derived from non-immune cells in the sera. Methods We conducted single-cell RNA sequence (scRNA-seq) on non-immune cells isolated from submandibular glands of IgG4-RD patients. We focused on fibroblasts expressing collagen type XV and confirmed the presence of those fibroblasts using immunohistochemistry. Additionally, we measured the levels of collagen type XV in the sera of IgG4-RD patients. Results The scRNA-seq analysis revealed several distinct clusters consisting of fibroblasts, endothelial cells, ductal cells, and muscle cells. Differential gene expression analysis showed upregulation of COL15A1 in IgG4-RD fibroblasts compared to control subjects. Notably, COL15A1-positive fibroblasts exhibited a distinct transcriptome compared to COL15A1-negative counterparts. Immunohistochemical analysis confirmed a significant presence of collagen type XV-positive fibroblasts in IgG4-RD patients. Furthermore, immune-suppressive therapy in active IgG4-RD patients resulted in decreased serum levels of collagen type XV. Conclusions Our findings suggest that collagen type XV-producing fibroblasts may represent a disease-characterizing non-immune cell population in IgG4-RD and hold potential as a disease-monitoring marker.

Background: Azacitidine (AZA) is the standard treatment for patients with high-risk myelodysplastic syndromes (MDS). The impact of skeletal muscle depletion (SMD), which is associated with outcomes of hematological malignancies, on the clinical course of MDS patients treated with AZA was investigated. Methods: This retrospective, observational study included 50 MDS patients treated with AZA. Muscle mass was evaluated using the skeletal muscle index (SMI), which is the area of muscle mass at the third lumbar vertebra on CT images divided by the square of the height. Results: Of the enrolled patients, 39 were males, and their median age was 69.5 years. Twenty-seven (20 male and 7 female) patients showed SMD. The median survival was 13.4 months in the SMD group and 15.2 months in the non-SMD group, with no significant difference and no significant association between the response rate or severe non-hematological toxicities and the presence of SMD. By contrast, grade 3–4 anemia and thrombocytopenia were significantly more frequent in the SMD group than in the non-SMD group. SMD was associated with severe anemia and thrombocytopenia in MDS patients treated with AZA. Conclusion: Reduced skeletal muscle mass may predict severe hematological toxicity in MDS patients treated with AZA.

Introduction Sigmoid conduit is one of the methods for achieving urinary diversion, but it is performed less frequently than ileal conduit and ureterostomy. Herein, we report a case in which a sigmoid colon conduit was performed after nephrostomy and transverse colostomy. Case presentation A 70‐year‐old man was referred to our hospital because of a bladder tumor. Computed tomography and transurethral biopsy revealed advanced bladder cancer with ureteral and rectal invasion. Despite drug therapy, the tumor progressed. Thus, nephrostomy and transverse colostomy were performed for urinary and fecal diversion, respectively. Subsequently, chemotherapy was administered for 8 months. As nephrostomy‐related complications occurred frequently during chemotherapy, a sigmoid colon conduit was performed instead of nephrostomy for urinary diversion to improve the patient's quality of life. Conclusion In patients with advanced bladder cancer requiring a double stoma of the urinary and fecal tracts, sigmoid colon conduit may be selected as a urinary diversion method.

This study is focused on hardware-based anonymization of location data for addressing privacy concerns while maintaining data utility in applications such as traffic-congestion prediction. The anonymization process involves approximating user location data to map intersections, identifying trajectories, and applying k-anonymization. However, the processing time in software implementation should be minimized. For real-time services, the process must be completed within 30 s to 1 min, which corresponds to the information update interval. Service requirements cannot be met when the volume of data and the scale of maps increase. To address this issue, we implemented a hardware accelerator on an field programmable gate array to perform the process with the aim of reducing the processing time. As a result, the maximum throughput of the proposed mechanism was approximately 150,000 data/s, which surpasses the target value of 130,000 data/s. The data retention rate, which represents information loss, was approximately 90% for the commonly used range of $10\le k\le 20$ . The difference in the data retention rate compared with the software implementation was approximately 1%. These results confirmed the effectiveness of the anonymization results obtained using the proposed mechanism.