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Japan is currently facing serious issues associated with an aging society and negative population growth. Urban structures, remnants of economic prosperity, are now hindrances to sustainable urban development, driving municipalities to seek efficient methods to manage this growth. Japanese municipalities continuously conduct surveys to collect data for urban planning purposes. However, lack of standardization and poor visualization tools prevent coordination and consensus-building among stakeholders during the planning process. The "i-Urban Revitalization" (i-UR) is an information infrastructure promoted by the Japanese government expected to enable municipalities to analyze and visualize their goals related to that process.This paper presents the implementation of i-UR. One approach employed for data standardization is to develop a CityGML Application Domain Extension (ADE) for urban planning that covers detailed attributes of city objects and mechanisms for global representation and analysis necessary for urban planning. The effectiveness of this ADE is being evaluated through data implementation and visualization experiments conducted in three municipalities in Japan. A prototype for the proposed "AR Consensus-formation system" is being developed for further utilization of the ADE. In addition, Ideathon events are being held to develop human resources in municipalities to promote urban revitalization and facilitate i-UR use. The ADE and i-UR tools described in this paper are expected to evolve based on feedback from users and experimental results.

This paper presents a novel structural image analysis method based on geometric optimization techniques towards automatic building change detection. The aim of this method is to efficiently detect the changes of various buildings such as small houses and houses with complex roof in an urban area from high resolution satellite imagery by comparing with spatial database (maps). The previous research has indicated of the effectiveness of a map-based building change detection approach, and further investigation suggests the following three problems; (1) the large diversity of building types, roof shape, roof materials, illumination condition and shadow, (2) the difficulty of imagery and maps matching which normally leads to considerable position error, (3) the capacity of extracting various types of newly-built buildings. To solve these problems, we propose a new geometric optimization method which consists of the following two steps; (1) the building recognition based on a combinatorial optimization method for optimal building boundary extraction, (2) the newly-built building extraction based on an optimal building hypothesis search method. The experimental results showed that the detection rate was approximately 89% for existing and changed buildings, and approximately 83% for newly-built buildings. These results demonstrate the effectiveness of the proposed geometric optimization methods to integrate bottom-up and top-down analysis. By combining the locally detected image features with consideration of regional contexts from map, our method can achieve highly accurate building change detection in urban area. The method has been applied to a building change detection service named "HouseDiff" and succeeded in assisting users.

Bacteremia due to Moraxella Catarrhalis is rare. An 85-year-old Japanese woman had productive cough, dyspnea, and fever. She had type 2 diabetes mellitus and chronic heart failure. Infiltration shown on chest radiography could be explained by heart failure or pneumonia. Initial blood culture yielded Gram-negative cocci, identified as M. catarrhalis . We therefore diagnosed cardiogenic pulmonary edema and M. catarrhalis pneumonia. M. catarrhalis has a high prevalence of β-lactamase production, so treatment comprised ampicillin/sulbactam. The clinical outcomes were favorable. Our case shows the importance of consideration of M. catarrhalis when patients with heart failure have pneumonia and the importance of blood culture for such patients.

Background: Blood culture is important in the diagnosis of blood infections and the identification of treatment strategies. Increased contamination in blood culture is a reduction in quality of care. This retrospective observational study, set in an emergency department in Japan, aims to elucidate the contamination rate before and after the introduction of contamination prevention activities., Methods: We compared the contamination rates before and one year after contamination prevention activities. Specifically, these activities included a novel and specific use of a blood culture cart and adherence to a checklist. The checklist included noting the actual site of collection, the method of disinfection, and whether gloves were worn., Results: There were 1184 and 1129 blood culture samples before and after the preventive activities, respectively. The rates of contamination were 2.03% (95% Cl = 1.30% to 3.00%) and 1.24% (95% Cl = 0.68% to 2.07%), respectively., Conclusion: Prevention activities including specific use of a blood culture cart and careful adherence to a checklist were not associated with a significant decrease in contamination rate in our hospital. Further studies based in hospitals with greater rates of contamination may see higher rates of reduction., (© 2025 John Wiley & Sons Ltd.)

SARS-CoV-2-related proteins, ACE2 and TMPRSS2, are determinants of SARS-CoV-2 infection. Although these proteins are expressed in oral-related tissues, their expression patterns and modulatory mechanisms in the salivary glands remain unknown. We herein showed that full-length ACE2, which has both a fully functional enzyme catalytic site and high-affinity SARS-CoV-2 spike S1-binding sites, was more highly expressed in salivary glands than in oral mucosal epithelial cells and the lungs. Regarding TMPRSS2, zymogen and the cleaved form were both expressed in the salivary glands, whereas only zymogen was expressed in murine lacrimal glands and the lungs. Metformin, an AMPK activator, increased stimulated saliva secretion and full-length ACE2 expression and decreased cleaved TMPRSS2 expression in the salivary glands, and exerted the same effects on soluble ACE2 (sACE2) and sTMPRSS2 in saliva. Moreover, metformin decreased the expression of beta-galactosidase, a senescence marker, and ADAM17, a sheddase of ACE2 to sACE2, in the salivary glands. In aged mice, the expression of ACE2 was decreased in the salivary glands, whereas that of sACE2 was increased in saliva, presumably by the up-regulated expression of ADAM17. The expression of TMPRSS2 in the salivary glands and sTMPRSS2 in saliva were both increased. Collectively, these results suggest that the protein expression patterns of ACE2 and TMPRSS2 in the salivary glands differ from those in other oral-related cells and tissues, and also that metformin and aging affect the salivary expression of ACE2 and TMPRSS2, which have the potential as targets for preventing the transmission of SARS-CoV-2., (© 2025 The Author(s). BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Background: Cholesterol embolism causes various organ dysfunctions, including skin, kidney, and gastrointestinal tract dysfunction, as well as immunological abnormalities, such as hypocomplementemia and eosinophilia. However, only a few cases of vasculitis accompanied by cholesterol embolism have been reported., Case Presentation: We present the case of an 82-year-old man with cholesterol embolism who also developed small-vessel vasculitis of the skin and muscles. The patient had a persistent fever, and blood tests showed eosinophilia and hypocomplementemia. Two months later, the patient developed a skin rash and myalgia in the thighs. Magnetic resonance imaging of the thighs revealed diffuse intramuscular hyperintensities on T2-weighted images and short tau inversion recovery sequences in the hamstrings and quadriceps femoris. Histological findings of the skin and muscle revealed small-vessel vasculitis, and random skin biopsy revealed cholesterol embolism. We diagnosed the patient with cholesterol embolism accompanied by small-vessel vasculitis of the skin and femoral muscles. Methylprednisolone was administered intravenously, and oral prednisolone was initiated. Muscle tenderness improved rapidly after the initiation of glucocorticoid therapy. However, he developed superior mesenteric artery embolization and died., Conclusions: Our case demonstrates that cholesterol embolism can be accompanied by small-vessel vasculitis of the skin and muscles., Competing Interests: Declarations. Ethics approval and consent to participate: This work obtained a waiver of approval from the Institutional Review Board of Kobe City Medical Center General Hospital. Consent for publication: Consent to publish the article was obtained from the patient. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In hospitalized patients, dermatologist intervention can lead to rapid identification and treatment of skin disease. However, many medical centers lack a specialized dermatologist, so skin biopsies might instead be performed by hospitalists. We aimed to determine the impact of skin biopsies performed by hospitalists on the diagnosis of skin conditions. Included in this study were adult patients who had skin biopsies performed for skin conditions by hospitalists at our hospital between 2012 and 2022. We retrospectively analyzed the diagnostic contribution rate before and after skin biopsy. Skin biopsies were performed on 49 patients, with 37 patients (75.5%) having biopsy in one location, 5 patients (10.2%) in two locations, and 7 patients (14.3%) in three locations. The average age was 63.5 [20.2] years, 55% of the patients were male and 12% had an in-hospital dermatologist consultation prior to assessment. IgA vasculitis was suspected in 9 patients (18.4%), and vasculitis, erythema nodosum, and intravascular lymphoma were each suspected in 4 patients (8.2%), respectively. IgA vasculitis was ultimately diagnosed in 10 patients (20.4%), polyarteritis nodosa in 3 patients (6.1%), and erythema nodosa in 3 patients (6.1%). Skin biopsy performed by hospitalists had a diagnostic contribution of 75.5%, with a change in diagnosis of 30.6% and a change in therapy of 14.3%. There was no difference in the rate of treatment changes according to the type of skin condition. Hospitalist-performed skin biopsies are suggested by our results to be limited, but still informative in healthcare facilities without a dedicated dermatologist., Competing Interests: Declarations Ethical approval and registration The study design was registered as a University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) Clinical Trial (UMIN trial ID: UMIN000050098) on 21 January, 2023 (UMIN-CTR URL:http://www.umin.ac.jp/ctr/index.htm). The study was approved by the Akashi Medical Center Research Ethics Committee (approval number: 2022-29). Informed consent was obtained in the form of opt-out system based on our website. All procedures were performed in accordance with the 1964 Declaration of Helsinki. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The periosteum is the layer of cells that covers nearly the entire surface of every bone. Upon infection, injury or malignancy the bone surface undergoes new growth-the periosteal reaction-but the mechanism and physiological role of this process remain unknown 1,2 . Here we show that the periosteal reaction protects against cancer invasion into the bone. Histological analyses of human lesions of head and neck squamous cell carcinomas (HNSCCs) show that periosteal thickening occurs in proximity to the tumour. We developed a genetically dissectible mouse model of HNSCC and demonstrate that inducible depletion of periosteal cells accelerates cancerous invasion of the bone. Single-cell RNA sequencing reveals that expression of the gene encoding the protease inhibitor TIMP1 is markedly increased in the periosteum at the pre-invasive stage. This increase is due to upregulation of HIF1α expression in the tumour microenvironment, and increased TIMP1 inactivates matrix-degrading proteases, promoting periosteal thickening to inhibit cancer invasion. Genetic deletion of Timp1 impairs periosteal expansion, exacerbating bone invasion and decreasing survival in tumour-bearing mice. Together, these data show that the periosteal reaction may act as a functional stromal barrier against tumour progression, representing a unique example of tissue immunity mediated by stromal cells., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Myocardial injury after non-cardiac surgery is due to ischaemia either during non-cardiac surgery or within 30 days after it. Our surveillance protocol includes hip fracture template and high-sensitivity troponin stratification, as recommended in European countries. Our retrospective study cohort included surgical patients for hip fracture at our hospital in Japan. The primary outcome was the rate of myocardial injury after non-cardiac surgery in comparison to patients managed with (213) and without (176) hip fracture template. The hip fracture template was used more in patients with myocardial injury after non-cardiac surgery than those without myocardial injury after non-cardiac surgery. When hip fracture template was used, patients had a higher likelihood of myocardial injury after non-cardiac surgery after adjusting for age, time to operation, diabetes mellitus, and chronic kidney disease (odds ratio 41.3; 95% confidence interval: 12.1, 259.6). Patients with myocardial injury after non-cardiac surgery had higher in-hospital mortality than those without myocardial injury after non-cardiac surgery, even in adjusted analysis. There was a high detection rate of myocardial injury after non-cardiac surgery when patients with hip fractures were managed with hip fracture template. Myocardial injury after non-cardiac surgery was associated with in-hospital mortality., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Giant cell arteritis (GCA) can result in visual loss and other sequelae. An 81-year-old man presented with a one-week history of fever. He had bilateral temporal headache, jaw claudication, tenderness of the temporal arteries and a recent skin rash. A temporal artery biopsy showed typical GCA, but the symptoms were self-limiting. We continued close observation, without administering prednisolone treatment. Five months later, the symptoms did not recur, and prednisolone again was not administered. Our patient presented with an atypical course of GCA that created a clinical dilemma. The final diagnosis was self-limiting GCA.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases worldwide. Some patients with MAFLD develop metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver fibrosis. However, the molecular mechanisms underlying this progression remain unknown, and no effective treatment for MASH has been developed so far. In this study, we performed a longitudinal detailed analysis of mitochondria in the livers of choline-deficient, methionine-defined, high-fat-diet (CDAHFD)-fed mice, which exhibited a MASH-like pathology. We found that FoF 1 -ATPase activity began to decrease in the mitochondria of CDAHFD-fed mice prior to alterations in the activity of mitochondrial respiratory chain complex, almost at the time of onset of liver fibrosis. In addition, the decrease in FoF 1 -ATPase activity coincided with the accelerated opening of the mitochondrial permeability transition pore (PTP), for which FoF 1 -ATPase might be a major component or regulator. As fibrosis progressed, mitochondrial permeability transition (PT) induced in CDAHFD-fed mice became less sensitive to cyclosporine A, a specific PT inhibitor. These results suggest that episodes of fibrosis might be related to the disruption of mitochondrial function via PTP opening, which is triggered by functional changes in FoF 1 -ATPase. These novel findings could help elucidate the pathogenesis of MASH and lead to the development of new therapeutic strategies.

We herein report a case of immune-mediated necrotizing myopathy (IMNM) in a patient with microscopic polyangiitis (MPA). A 77-year-old Japanese woman presented with a 2-day history of proximal muscle weakness and myalgia, with elevated serum creatinine kinase (CK) levels. Findings of a muscle biopsy were compatible with IMNM; however, anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies were negative. She also had peripheral neuropathy with elevated serum myeloperoxidase anti-neutrophil cytoplasmic antibody titers, leading to a diagnosis of MPA. IMNM can be a pathological result of MPA muscle involvement.

The chromosome passenger complex (CPC) is a kinase complex formed by Aurora B, borealin, survivin and inner centromere protein (INCENP). The CPC is active during mitosis and contributes to proper chromosome segregation via the phosphorylation of various substrates. Overexpression of each CPC component has been reported in most cancers. However, its significance remains unclear, as only survivin is known to confer chemoresistance. This study showed that the overexpression of borealin, a CPC component, stabilized survivin protein depending on its interaction with survivin. Unexpectedly, the accumulation of survivin by borealin overexpression did not affect the well-characterized functions of survivin, such as chemoresistance and cell proliferation. Interestingly, the overexpression of borealin promoted lactate production but not the overexpression of the deletion mutant that lacks the ability to bind to survivin. Consistent with these findings, the expression levels of glycolysis-related genes were enhanced in borealin-overexpressing cancer cells. Meanwhile, the overexpression of survivin alone did not promote lactate production. Overall, the accumulation of the borealin-survivin complex promoted glycolysis in squamous cell carcinoma cells. This mechanism may contribute to cancer progression via excessive lactate production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Medullary thymic epithelial cells (mTECs) are essential for the establishment of self-tolerance in T cells. Promiscuous gene expression by a subpopulation of mTECs regulated by the nuclear protein Aire contributes to the display of self-genomic products to newly generated T cells. Recent reports have highlighted additional self-antigen-displaying mTEC subpopulations, namely Fezf2-expressing mTECs and a mosaic of self-mimetic mTECs including thymic tuft cells. In addition, a functionally different subset of mTECs produces chemokine CCL21, which attracts developing thymocytes to the medullary region. Here, we report that CCL21 + mTECs and Aire + mTECs non-redundantly cooperate to direct self-tolerance to prevent autoimmune pathology by optimizing the deletion of self-reactive T cells and the generation of regulatory T cells. We also detect cooperation for self-tolerance between Aire and Fezf2, the latter of which unexpectedly regulates thymic tuft cells. Our results indicate an indispensable interplay among functionally diverse mTECs for the establishment of central self-tolerance., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Purpose: Hip fractures are associated with high morbidity and mortality, the rates of which can be improved by comprehensive care. To improve hospitalist co-management of hip fractures, we designed and implemented hip fracture template (HFT), a flagging and risk stratification algorithm system. It includes consideration of perioperative management and preventative measures against hip fractures. We examined its effect on morbidity in patients with hip fractures and the factors associated with complications., Methods: We conducted a retrospective cohort study of patients who underwent surgery for hip fracture. The primary outcome was the perioperative complication rate, comparing patients managed with and without HFT. Multivariate analysis was adjusted for age, gender, and any significant variables shown in univariate analysis., Results: HFT was used in 121 patients and not used in 147 patients. In univariate analysis, patients were less likely to have complications if HFT was used (19.0% vs. 29.9%, P  = 0.047), but there was no difference in length of stay (17 days vs. 17 days, P  = 0.27) or in-hospital-mortality (0.8% vs. 0.7%, P  = 1.00) between the groups. In adjusted analysis, patients managed by HFT had lower likelihood of complications (OR 0.55, 95% CI 0.31-0.98). Among patients managed by HFT, those with revised cardiac risk index (RCRI) ≥ 1 were more likely to have complications in both univariate (42.1% vs. 14.7%, P  = 0.01) and adjusted analysis (OR 3.37, 95% CI 1.03-10.84)., Conclusion: Patients with hip fractures managed with HFT were less likely to have complications, especially those with RCRI ≥ 1, suggesting benefits of using HFT., Competing Interests: Conflict of interestAll authors have no conflicts of interest., (© Indian Orthopaedics Association 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Venous congestion is a possible cause of ischemic colitis following colorectal surgery. As such, congestive ischemic colitis should be considered in such cases where the mesenteric artery is preserved. Herein, we describe the case of a 73-year-old man who presented to the hospital with a two-week history of difficult defecation and frequent mucous stools and was subsequently diagnosed with refractory ischemic enterocolitis due to venous congestion. The patient had undergone resection of the sigmoid colon cancer with preservation of the inferior mesenteric artery 11 months before presentation. Contrast-enhanced abdominal computed tomography revealed edematous wall thickening on the anal side of the anastomosis. A colonoscopy revealed a normal mucosa extending from the anastomosis to the descending colon; however, mucosal swelling, erythema, and erosion were observed on the rectal side of the anastomosis. Based on these findings, he was diagnosed with ischemic colitis. After two months of ineffective conservative treatment, the patient underwent surgery. Ischemic colitis was diagnosed as venous congestion based on the histopathological examination. Preservation of the mesenteric artery may result in ischemic colitis due to an imbalance between the arterial and venous blood flow. Chronic ischemic colitis due to venous congestion should be considered in cases of mesenteric artery preservation to reduce anastomotic leakage., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ishimaru et al.)

Background: Comprehending the molecular mechanisms underlying head and neck squamous cell carcinoma (HNSCC) is vital for the development of effective treatment strategies. Deubiquitinating enzymes (DUBs), which regulate ubiquitin-dependent pathways, are potential targets for cancer therapy because of their structural advantages. Here we aimed to identify a potential target for HNSCC treatment among DUBs., Methods: A screening process was conducted using RNA sequencing data and clinical information from HNSCC patients in the TCGA database. A panel of 88 DUBs was analyzed to identify those associated with poor prognosis. Subsequently, HNSCC cells were modified to overexpress specific DUBs, and their effects on cell proliferation and invasion were evaluated. In vivo experiments were performed to validate the findings., Results: In HNSCC patients, USP10, USP14, OTUB1, and STAMBP among the screened DUBs were associated with a poor prognosis. Among them, OTUB1 showed the most aggressive characteristics in both in vitro and in vivo experiments. Additionally, OTUB1 regulated the stability and nuclear localization of YAP1, a substrate involved in cell proliferation and invasion. Notably, OTUB1 expression exhibited a positive correlation with the HNSCC-YAP score in HNSCC cells., Conclusions: This study highlights the critical role of OTUB1 in HNSCC progression via modulating YAP1. Targeting the OTUB1-YAP1 axis holds promise as a potential therapeutic strategy for HNSCC treatment., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Cells sense and respond to extracellular mechanical stress through mechanotransduction receptors and ion channels, which regulate cellular behaviors such as cell proliferation and differentiation. Among them, PIEZO1, piezo-type mechanosensitive ion channel component 1, has recently been highlighted as a mechanosensitive ion channel in various cell types including mesenchymal stem cells. We previously reported that PIEZO1 is essential for ERK1/2 phosphorylation and osteoblast differentiation in bone marrow-derived mesenchymal stem cells (BMSCs), induced by hydrostatic pressure loading and treatment with the PIEZO1-specific activator Yoda1. However, the molecular mechanism underlying how PIEZO1 induces mechanotransduction remains unclear. In this study, we investigated that the role of the C-terminus in regulating extracellular Ca 2+ influx and activating the ERK1/2 signaling pathway. We observed the activation of Fluo-4 AM in the Yoda1-stimulated human BMSC line UE7T-13, but not in a calcium-depleted cell culture medium. Similarly, Western blotting analysis revealed that Yoda1 treatment induced ERK1/2 phosphorylation, but this induction was not observed in calcium-depleted cell culture medium. To investigate the functional role of the C-terminus of PIEZO1, we generated HEK293 cells stably expressing the full-length mouse PIEZO1 (PIEZO1-FL) and a deletion-type PIEZO1 lacking the C-terminal intracellular region containing the R-Ras-binding domain (PIEZO1-ΔR-Ras). We found that Yoda1 treatment predominantly activated Flou-4 AM and ERK1/2 in PIEZO1-FL-trasfected cells but neither in PIEZO1-ΔR-Ras-transfected cells nor control cells. Our results indicate that the C-terminus of PIEZO1, which contains the R-Ras binding domain, plays an essential role in Ca 2+ influx and activation of the ERK1/2 signaling pathway, suggesting that this domain is crucial for the mechanotransduction of osteoblastic differentiation in BMSCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that might affect the research reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Autoimmune factor XIII/13 deficiency (aFXIII deficiency) is a rare hemorrhagic disorder, for which typical guideline-directed treatment is aggressive immunosuppressive therapy. Approximately 20% of patients are over 80 years old; however, and optimum management of such patients has not reached consensus. Our elderly patient had massive intramuscular hematoma, and aFXIII deficiency was diagnosed. The patient opted against aggressive immunosuppressive therapy, so he was managed with conservative treatment only. Thorough survey of other correctable causes of bleeding and anemia is also required in similar cases. Our patient's serotonin-norepinephrine reuptake inhibitor use and multivitamin deficiency (vitamin C, B 12 and folic acid) were revealed to be aggravating factors. Fall prevention and muscular stress prevention are also important in elderly patients. Our patient had two relapses of bleeding within 6 months, which were improved spontaneously by bed rest without factor XIII replacement therapy or blood transfusion. Conservative management may be preferred for frail and elderly patients with aFXIII deficiency when they opt against standard therapy., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: In Japan, the benefits of hospitalist physician-led care after heart failure have not been sufficiently demonstrated. We evaluated quality of care by the general internal medicine hospitalist (GIM-H) system for patients after acute heart failure and compared it with care by cardiologists., Methods: This retrospective cohort study enrolled adult patients from within a two-year period who were admitted to our institution for heart failure. Primary outcome measures were medico-economic indicators: length of hospital stay and medical costs. Secondary outcomes included readmission within 30 days of discharge, death within 30 days of admission, rate of prescription of ACEI/ARB and beta-blockers for heart failure with reduced left ventricular ejection fraction, and the percentage of patients receiving bespoke written treatment plans after discharge. This was thought to represent quality of heart failure-specific care. Outcomes between the groups were compared by adjusting for background factors using a propensity score., Results: We enrolled 404 patients, and 81 were assigned to each group after matching (mean age: 86 years, female: 64.2%, mean left ventricular ejection fraction: 53.2%). The GIM-H-treated group had a significantly shorter hospital stay (13.7 days vs. 21.8 days, P < 0.001), a significantly lower total medical cost (618,805 JPY vs. 867,857 JPY, P < 0.05) but a higher medical cost per day (48,010 JPY vs 42,813 JPY, P < 0.05) than the cardiologist-treated group. Other indicators were not significantly different., Conclusions: : GIM-H physicians in Japan are suggested to be useful and effective in care of patients with heart failure. The hospitalist system may positively impact the health economic outcomes of such patients.

Introduction: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that affects the function of exocrine glands, such as the lacrimal and the salivary glands. Extraglandular lesions and malignant lymphoma also occur during the progressive stage of pSS. We have, herein, focused on the pulmonary lesions of pSS and have aimed clarifying their pathophysiological mechanism by comparing the glandular with the extraglandular lesions observed in a mouse model of pSS., Results: The histopathological analysis of lung tissues obtained from NFS/ sld mice that have undergone neonatal thymectomy was performed. Moreover, in vivo and in vitro experiments were conducted along with immunological analyses in order to characterize the unique phenotypes of the pulmonary lesions identified in these pSS model mice. Inflammatory lesions with a bronchus-associated lymphoid tissue-like structure were identified in the lungs of pSS model mice. In addition, relative to salivary gland lesions, pulmonary lesions showed increased CD23 + follicular B (FB) cells. In vitro and pulmonary B cells were more readily driven to CD23 + FB cell phenotype than salivary gland B cells in pSS model mice. Furthermore, the CD23 + FB cell differentiation was found to be enhanced in a CD4 + T-cell-dependent manner under a Th2-type condition in the lungs of herein examined pSS model mice., Discussion: A Th2-type response in the pSS lung may promote the progression of autoimmune lesions through an enhanced abnormal differentiation of B cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sato-Fukuba, Arakaki, Ushio, Otsuka, Nagao, Matsuzawa, Tawara, Tsunematsu and Ishimaru.)

Iroquois homeobox (Irx) genes are TALE-class homeobox genes that are evolutionarily conserved across species and have multiple critical cellular functions in fundamental tissue development processes. Previous studies have shown that Irxs genes are expressed during tooth development. However, the precise roles of genes in teeth remain unclear. Here, we demonstrated for the first time that Irx3 is an essential molecule for the proliferation and differentiation of odontoblasts. Using cDNA synthesized from postnatal day 1 (P1) tooth germs, we examined the expression of all Irx genes (Irx1-Irx6) by RT-PCR and found that all genes except Irx4 were expressed in the tooth tissue. Irx1-Irx3 a were expressed in the dental epithelial cell line M3H1 cells, while Irx3 and Irx5 were expressed in the dental mesenchymal cell line mDP cells. Only Irx3 was expressed in both undifferentiated cell lines. Immunostaining also revealed the presence of IRX3 in the dental epithelial cells and mesenchymal condensation. Inhibition of endogenous Irx3 by siRNA blocks the proliferation and differentiation of mDP cells. Wnt3a, Wnt5a, and Bmp4 are factors involved in odontoblast differentiation and were highly expressed in mDP cells by quantitative PCR analysis. Interestingly, the expression of Wnt5a (but not Wnt3a or Bmp4) was suppressed by Irx3 siRNA. These results suggest that Irx3 plays an essential role in part through the regulation of Wnt5a expression during odontoblast proliferation and differentiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that might affect the research reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Aspiration pneumonia is a challenge in Japan, with many elderly citizens; however, there are insufficient experts on swallowing. Non-expert doctors may suspend oral intake for an overly long period because of the fear of further aspiration. We devised and modified an assessment protocol for swallowing function with reference to the Japanese and American practical guidelines for dysphagia. This study aimed to demonstrate clinical decision-making using the protocol by reporting the results of decisions on the safe and timely restart of adequate food intake for patients with aspiration pneumonia. Patients and Methods: This comparative retrospective study included 101 patients hospitalized with aspiration pneumonia between April 2015 and November 2017. We compared the parameters of patients for whom decisions on resumption of oral intake were aided by our protocol against those of patients from the previous year when the protocol was not used. We counted the days until either resumption of oral intake or events of aspiration/choking. Results: The duration of days until oral intake in the two groups was 1.64 ± 2.34 days in the protocol group (56 patients) and 2.09 ± 2.30 days in the control group (45 patients) ( P =0.52). The adverse events of aspiration/choking were less frequent in the protocol group (5 vs. 15, odds ratio (OR) 0.32, P <0.001) as compared to the control group. The protocol group showed a significant reduction in aspiration/choking (OR 0.19, P <0.01). Conclusion: Clinical decision-making based on the protocol seems to help non-expert doctors make informed decisions regarding resuming oral intake after aspiration pneumonia., (©2023 The Japanese Association of Rural Medicine.)

It recently has been reported that partial-epithelial-mesenchymal transition (p-EMT) program is associated with metastasis in head and neck squamous cell carcinoma (HNSCC). We previously have identified POSTN (which encodes periostin) as an invasion-promoting molecule in HNSCC. Interestingly, POSTN expression is frequently observed in cancer cells with higher p-EMT score by using a previous single-cell transcriptomic data of HNSCC cases. Although it is known that POSTN has 11 splicing variants, the role of them has not been determined in HNSCC. Here, we found that HNSCC cells with EMT features expressed POSTN isoforms, Iso3 (lacking exon 17 and 21) and Iso5 (lacking exon 17), whereas fibroblast expressed Iso3 and Iso4 (lacking exon 17, 18, and 21). The expression of POSTN Iso3 and Iso4 are known to be widely observed in various cell types including stromal cells. Therefore, we focused on the role of novel cancer cell-derived POSTN isoform, Iso5, in HNSCC. Single overexpression of POSTN Iso5 as well as Iso3 promoted invasion. Surprisingly, Iso5 synergistically promoted invasion together with Iso3. Notably, Iso5 as well as Iso3 upregulated p-EMT-related genes. We suggest that a novel cancer-specific POSTN isoform lacking exon 17 (Iso5) can be a useful marker for detecting cancer cells undergoing p-EMT. Moreover, a POSTN Iso5 can be a novel target for diagnosis and therapy in HNSCC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To determine the incidence of bacteremia in patients with DKA., Methods: We conducted a cross-sectional study of patients aged 18 years and older with a principal diagnosis of DKA or hyperglycemic hyperosmotic syndrome (HHS) who presented to our community hospital between 2008 and 2020. Using medical records from initial visits, we retrospectively calculated the incidence of bacteremia. This was defined as the percentage of subjects with positive blood cultures except for those with contamination., Results: Among 114 patients with hyperglycemic emergency, two sets of blood cultures were collected in 45 of 83 patients with DKA (54%), and 22 of 31 patients with HHS (71%). The mean age of patients with DKA was 53.7 years (19.1) and 47% were male, while the mean age of patients with HHS was 71.9 years (14.9) and 65% were male. The incidences of bacteremia and blood culture positivity were not significantly different between patients with DKA and those with HHS (4.8% vs. 12.9%, P = 0.21 and 8.9% vs. 18.2%, P = 0.42, respectively). Urinary tract infection was the most common concomitant infection of bacteria, with E. coli as the main causative organism., Conclusion: Blood cultures were collected in approximately half of the patients with DKA, despite a nonnegligible number of them testing positive in blood culture. Promoting awareness of the need for taking blood culture is imperative for the early detection and management of bacteremia in patients with DKA., Clinical Trial Registration: UMIN trial ID - UMIN000044097; jRCT trial ID - jRCT1050220185.

Background: Crowned dens syndrome (CDS) is characterized by calcification around the odontoid process, accompanied by neck pain. Although CDS is supposedly rare, we regularly diagnose and manage this condition, indicating a perception gap between previous studies and our experience. The purpose of this study was to determine the annual incidence of CDS, time to diagnosis in CDS, as well as the features of CDS., Methods: The study design was a retrospective case series study conducted at eight teaching hospitals in Japan. We identified CDS cases from April 2013-March 2015. CDS was diagnosed when patients had acute onset of neck pain and CT showed calcification around the dens and when other diagnoses were unlikely., Results: Seventy-two CDS cases were identified. Mean annual incidence was 4.6 ± 2.3 cases at each hospital. Among those with available data, 57 of 64 had limited rotation (89.1%). The diagnosis of CDS was made in general internal medicine or the emergency medicine department in 61 cases (84.7%). A total of 62 cases (86.1%) were diagnosed within 1 day of presentation, and the median time from initial presentation at the hospital to diagnosis was 0.0 days (25th-75th percentiles, 0.0-1.0). For treatment, NSAIDs were used in 56cases (77.8%) and acetaminophen in 20 cases (27.8%)., Conclusion: CDS might be more common than has been reported to date. Time to diagnosis of CDS was within 1 day of visiting a teaching hospital. Cervical motion restriction is common in CDS and may be useful in establishing the diagnosis., Competing Interests: The authors declare no conflicts of interest for this article., (© 2023 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.)

An 83-year-old woman with asymptomatic pulmonary sarcoidosis presented to our hospital with fever and malaise for three months. Abdominal CT showed splenomegaly, and bone marrow examination revealed non-caseating granulomas. Pancytopenia was diagnosed due to bone marrow and splenic lesions of sarcoidosis. Steroid pulses were administered, but the patient died without response to treatment. Pathological autopsy results showed non-caseating granulomas and hemophagocytosis in the spleen and bone marrow. This suggested hemophagocytic syndrome, which was not suspected before death, in addition to sarcoidosis. In patients with splenomegaly and pancytopenia with history of pulmonary sarcoidosis, hemophagocytic syndrome should be considered in differential diagnosis.

Objectives: The aim of this study was to examine whether the distance between the skin and the renal pelvis affects the detection of costovertebral angle (CVA) tenderness in patients with acute focal bacterial nephritis (AFBN)., Methods: We retrospectively reviewed the charts of our patients between April 2013 and June 2019 who were diagnosed as having AFBN. Diagnosis was based on ultrasound or computed tomography with contrast, revealing at least one wedge-shaped area of decreased vascularity and confirmation of fever not attributable to another condition., Results: We extracted 23 cases, all Japanese (mean age 60.0 years old [range 45-81 years], 7 males, 16 females). CVA tenderness was present in 8 of these 23 patients. Receiver operating characteristic curves were drawn to evaluate the ability to differentiate skin-to-renal pelvis distance (SPD), body mass index, and age. Only SPD was a useful predictor of CVA tenderness, and 66 mm was determined as the optimal cutoff point (area under the receiver operating characteristic curve 0.858, 95% confidence interval 0.70-1.00). Logistic regression analysis was performed with CVA tenderness as a dependent variable, and SPD, body mass index, and age as explanatory variables. SPD was an independent predictive variable of CVA tenderness ( P = 0.038, odds ratio 0.76, 95% confidence interval 0.590-0.986)., Conclusions: CVA tenderness showed low yield in the diagnosis of AFBN in patients with longer SPD. Its use for diagnosis in obese patients may therefore be limited.