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Abstract Tests to detect mild cognitive impairment (MCI) should have high sensitivity and accuracy. Previously, we reported on a cognitive composition test (CCT) that we developed to detect MCI. In this study, we compared gaze behavior parameters, namely, gaze fixation duration and gaze-shift frequency, during the CCT in participants with MCI and healthy controls (HC) to determine whether these parameters would accurately detect MCI in older adults. Participants performed CCT-A, -B, and -C tasks with varying difficulty levels while wearing eye-tracking devices. Performance time, gaze fixation duration, and gaze-shift frequency were analyzed. Receiver operating characteristic curve analysis was performed to assess the identification accuracy. The MCI group was significantly slower in completing the CCT-C task and had a higher gaze-shift frequency into both the sample object space and workspace than the HC group. Gaze fixation duration in the sample object space increased in the MCI group as the CCT became difficult. Our findings indicated that combining the CCT with performance time and gaze pattern improved the accuracy of distinguishing between individuals with and without MCI and that patients with MCI have abnormal gaze behavior during cognitive tasks. Therefore, evaluation of gaze parameters may improve the accuracy of identifying patients with MCI.

Abstract Background Immune checkpoint inhibitors (ICIs) are crucial in cancer treatment; however, they carry the risk of immune-related adverse events (irAEs), such as enteritis. Case presentation: This study investigated the role of the gut microbiota during the onset and remission of irAE enteritis in a patient with stage IV melanoma undergoing anti-PD-1 and anti-CTLA-4 therapy. Following commencement of ICI treatment, the patient developed severe diarrhea and was diagnosed with grade 3 irAE enteritis. Steroid and probiotic treatments provided swift symptom relief and remission, as confirmed by reduced fecal calprotectin levels and gastrointestinal imaging. Microbiota diversity analysis conducted via 16S rRNA gene sequencing identified a decrease in Streptococcus prevalence with improvement in enteritis symptoms. Conversely, genera Fusobacterium, Faecalibacterium, Bacteroides, Prevotella, and Bifidobacterium showed increased representation after remission. These genera are associated with anti-inflammatory properties and fibrous substrate degradation, aiding gut health. Immunological assessment demonstrated fluctuations in cytokine expression and the modulation of costimulatory molecules, aligning with therapeutic interventions and microbiota alterations. Conclusions Our findings indicate a significant correlation between gut microbiota and immune responses in irAE enteritis. This underscores the potential utility of microbiome profiling in predicting irAE occurrence and in providing treatment strategies, thereby promoting a more comprehensive approach to managing the adverse effects of ICIs.

Objective To evaluate the preoperative and perioperative predictors of persistent leg numbness following lumbar fusion in patients aged ≥ 75 years. Methods This single-center retrospective study examined 304 patients aged ≥ 75 years who underwent lumbar fusion for lumbar degenerative disease (102 men, 202 women; mean age, 79.2 [75–90] years). The visual analogue scale (VAS) score for leg numbness was examined preoperatively and at 2 years postoperatively. The persistent leg numbness group included patients with a 2-year postoperative VAS score for leg numbness ≥ 5 points. The demographic data were also reviewed. A multivariate stepwise logistic regression analysis was performed for variables with univariate analysis values of p < 0.2 on univariate analysis. Results In total, 71 patients (23.4%) experienced persistent postoperative leg numbness. Multivariate logistic regression analysis revealed that a history of lumbar decompression, longer symptom duration, and a preoperative VAS score for leg numbness ≥ 5 points were associated with greater postoperative persistent leg numbness following lumbar fusion. In contrast, other factors, such as sex, body mass index, vertebral fracture, diabetes mellitus, depression, symptom duration, dural injury, operative time, and estimated blood loss, were not. Conclusion A history of preoperative lumbar decompression, longer symptom duration, and greater preoperative VAS scores for leg numbness were preoperative predictors of persistent postoperative leg numbness following lumbar fusion in older patients. Although lumbar fusion is expected to improve leg numbness, surgeons should consider the surgical history, duration, and preoperative numbness intensity and explain the potential postoperative persistent leg numbness in advance.

Graphical Abstract

3D multicellular self-organized cluster models, e.g., organoids are promising tools for developing new therapeutic modalities including gene and cell therapies, pharmacological mechanistic and screening assays. Various applications of these models have been used extensively for decades, however, the mechanisms of cluster formation, maintenance, and degradation of these models are not even known over in-vitro-life-time. To explore such advantageous models mimicking native tissues or organs, it is necessary to understand aforementioned mechanisms. Herein, we intend to clarify the mechanisms of the formation of cell clusters. We previously demonstrated that primary chondrocytes isolated from distinct longitudinal depth zones in articular cartilage formed zone-specific spherical multicellular clusters in vitro. To elucidate the mechanisms of such cluster formation, we simulated it using the computational Cellular Potts Model with parameters were translated from gene expression levels and histological characteristics corresponding to interactions between cell and extracellular matrix. This simulation in silico was validated morphologically with cluster formation in vitro and vice versa. Since zone specific chondrocyte cluster models in silico showed similarity with corresponding in vitro model, the in silico has a potential to be used for prediction of the 3D multicellular in vitro models used for development, disease, and therapeutic models.

An identical group of disorders has been called “interstitial granulomatous dermatitis” and “palisaded neutrophilic and granulomatous dermatitis.” In addition, a drug-induced subset of this condition has been named “interstitial granulomatous drug reaction (IGDR).” More recently, “reactive granulomatous dermatitis (RGD)” has been proposed as an umbrella term encompassing these three disorders. A considerable number of RGD cases are associated with systemic conditions, including autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, inflammatory bowel disease, and malignancies. IGDR has also been shown to be caused by certain medications. We present a case of a 74-year-old Japanese man showing an asymptomatic, well-demarcated erythema eruption on the bilateral inguinal region extending to the lower abdomen and proximal thigh area. He had hyperlipidemia and had been taking pravastatin for 4 years. A biopsy specimen taken from the erythematous lesion revealed infiltration of lymphocytes and histiocytes in the upper and lower dermis. Interstitial infiltrates of histiocytes and lymphocytes were found as they were dispersed between collagen bundles. Immunostaining showed CD68+ macrophages intermingled with CD4+ and CD8+ T cells. Based on the clinical and histologic findings, the eruption was diagnosed as RGD. Because of the possibility of IGDR, pravastatin was stopped. His eruption completely disappeared within 6 months after the discontinuation. The list of drugs that cause RGD includes angiotensin-converting enzyme inhibitors, antihistamines, β-blockers, antidepressants, anticonvulsants, tocilizumab and ustekinumab. In addition, various statins have been reported to induce drug eruptions. The eruption types are mainly eczematous or lichenoid reactions, with psoriasiform or ichthyosiform reactions occurring rarely. There was only one report documenting that RGD occurred in patients administered rosuvastatin, with annular, violaceous plaques distributed on the extremities, proximal trunk and intertriginous areas. Pravastatin induces lichenoid eruption, but RGD has not been documented. Our case suggests that RGD is underestimated as an adverse effect of statins possibly because of its unusual cutaneous manifestations.

Abstract Background Rainfall-induced floods represented 70% of the disasters in Japan from 1985 to 2018 and caused various health problems. To improve preparedness and preventive measures, more information is needed on the health problems caused by heavy rain. However, it has proven challenging to collect health data surrounding disasters due to various inhibiting factors such as environmental hazards and logistical constraints. In response to the Kumamoto Heavy Rain 2020, Emergency Medical Teams (EMTs) used J-SPEED (Japan-Surveillance in Post Extreme Emergencies and Disasters) as a daily reporting tool, collecting patient data and sending it to an EMTCC (EMT Coordination Cell) during the response. We performed a descriptive epidemiological analysis using J-SPEED data to better understand the health problems arising from the Kumamoto Heavy Rain 2020 in Japan. Methods During the Kumamoto Heavy Rain 2020 from July 5 to July 31, 2020, 79 EMTs used the J-SPEED form to submit daily reports to the EMTCC on the number and types of health problems they treated. We analyzed the 207 daily reports, categorizing the data by age, gender, and time period. Results Among the 816 reported consultations, women accounted for 51% and men accounted for 49%. The majority of patients were elderly (62.1%), followed by adults (32.8%), and children (5%). The most common health issues included treatment interruption (12.4%), hypertension (12.0%), wounds (10.8%), minor trauma (9.6%), and disaster-related stress symptoms (7.4%). Consultations followed six phases during the disaster response, with the highest occurrence during the hyperacute and acute phases. Directly disaster-related events comprised 13.9% of consultations, indirectly related events comprised 52.0%, and unrelated events comprised 34.0%. As the response phases progressed, the proportions of directly and indirectly related events decreased while that of unrelated events increased. Conclusion By harnessing data captured by J-SPEED, this research demonstrates the feasibility of collecting, quantifying, and analyzing data using a uniform format. Comparison of the present findings with those of two previous analyses of J-SPEED data from other disaster scenarios that varied in time, location, and/or disaster type showcases the potential to use analysis of past experiences to advancing knowledge on disaster medicine and disaster public health.

Abstract Recent research has highlighted the importance of the gut microbiome in regulating aging, and probiotics are interventions that can promote gut health. In this study, we surveyed several novel lactic acid bacteria to examine their beneficial effect on organismal health and lifespan in C. elegans. We found that animals fed some lactic acid bacteria, including L. acidophilus 1244 and L. paracasei subsp. paracasei 2004, grew healthy. Supplementation with the lactic acid bacterial strains L. acidophilus 1244 or L. paracasei subsp. paracasei 2004 significantly improved health, including food consumption, motility, and resistance to oxidative stressor, hydrogen peroxide. Our RNA-seq analysis showed that supplementation with L. paracasei subsp. paracasei 2004 significantly increased the expression of daf-16, a C. elegans FoxO homolog, as well as genes related to the stress response. Furthermore, daf-16 deletion inhibited the longevity effect of L. paracasei subsp. paracasei 2004 supplementation. Our results suggest that L. paracasei subsp. paracasei 2004 improves health and lifespan in a DAF-16-dependent manner.

Thioredoxin-interacting protein (TXNIP) plays an important role in glucose metabolism, and its expression is regulated by DNA methylation (DNAm). Although the association between TXNIP DNAm and type 2 diabetes mellitus has been demonstrated in studies with a cross-sectional design, prospective studies are needed. We therefore examined the association between TXNIP DNAm levels and longitudinal changes in glycemic traits by conducting a longitudinal study involving 169 subjects who underwent two health checkups in 2015 and 2019. We used a pyrosequencing assay to determine TXNIP DNAm levels in leukocytes (cg19693031). Logistic regression analyses were performed to assess the associations between dichotomized TXNIP DNAm levels and marked increases in glycemic traits. At four years, the TXNIP DNA hypomethylation group had a higher percentage of changes in fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) compared to those in the hypermethylation group. The adjusted odds ratios for FPG and HbA1c levels were significantly higher in the TXNIP DNA hypomethylation group than in the hypermethylation group. We found that TXNIP DNA hypomethylation at baseline was associated with a marked increase in glycemic traits. Leukocyte TXNIP DNAm status could potentially be used as an early biomarker for impaired glucose homeostasis.

Objective To elucidate the patient characteristics and outcomes of emergency surgery for spinal metastases and identify risk factors for emergency surgery. Methods We prospectively analyzed 216 patients with spinal metastases who underwent palliative surgery from 2015 to 2020. The Eastern Cooperative Oncology Group performance status, Barthel index, EuroQol-5 dimension (EQ5D), and neurological function were assessed at surgery and at 1, 3, and 6 months postoperatively. Multivariate analysis was performed to identify risk factors for emergency surgery. Results In total, 146 patients underwent nonemergency surgery and 70 patients underwent emergency surgery within 48 hours of diagnosis of a surgical indication. After propensity score matching, we compared 61 patients each who underwent nonemergency and emergency surgery. Regardless of matching, the median performance status and the mean Barthel index and EQ5D score showed a tendency toward worse outcomes in the emergency than nonemergency group both preoperatively and 1 month postoperatively, although the surgery greatly improved these values in both groups. The median survival time tended to be shorter in the emergency than nonemergency group. The multivariate analysis showed that lesions located at T3–10 (p = 0.002; odds ratio [OR], 2.92; 95% confidence interval [CI], 1.48–5.75) and Frankel grades A–C (p < 0.001; OR, 4.91; 95% CI, 2.45–9.86) were independent risk factors for emergency surgery. Conclusion Among patients with spinal metastases, preoperative and postoperative subjective health values and postoperative survival are poorer in emergency than nonemergency surgery. Close attention to patients with T3–10 metastases is required to avoid poor outcomes after emergency surgery.

Oxymethylene dimethyl ether (OME) is a promising carbon neutral fuel for reducing well-to-wheel CO2 emission and expected to suppress soot formation due to the lack of C-C bond. The present study aims to develop a chemical reaction model to predict soot formation processes of OME3. Initial reaction processes of OME3 within 10 ns after the onset of reaction were traced using molecular dynamics simulation under various Φ-T conditions (Φ: equivalence ratio, T: temperature), and reasonably converted to a chemical reaction model. The model was coupled with a conventional soot formation model for paraffinic fuels, which enables to simulate soot formation processes of OME3. The Φ-T map of soot yield for OME3 was calculated and it appeared that OME3 can largely suppress soot formation compared with n-hexane as a paraffin fuel. Reaction path analysis revealed that the formation of unsaturated C2 species for OME3 is delayed and reduced compared with n-hexane, which leads to the soot suppression effect of OME3.

Abstract The renal angina index (RAI) is a validated scoring tool for predicting acute kidney injury (AKI). We investigated the efficacy of the RAI in 2436 heterogeneous patients (mean age, 70 years) treated in cardiac intensive care units (CICUs). The RAI was calculated from creatinine and patient condition scores. AKI was diagnosed by the Kidney Disease: Improving Global Outcome criteria. The primary and secondary endpoints were the development of severe AKI and all-cause mortality, respectively. Four hundred thirty-three patients developed AKI, 87 of them severe. In multivariate analyses, the RAI was a significant independent predictor of severe AKI. During the 12-month follow-up period, 210 patients suffered all-cause death. Elevated RAI was independently associated with all-cause mortality, as was NT-proBNP (p

AbstractYKL-40 is implicated in inflammation and tissue repair, but no reports have investigated its involvement in myositis in polymyositis (PM) and dermatomyositis (DM). Therefore, we aimed to investigate the relationship between YKL-40 and PM/DM. We retrospectively enrolled 35 patients diagnosed with PM/DM along with 26 healthy controls (HCs). Both PM and DM were diagnosed according to Bohan and Peter’s criteria. Serum YKL-40 levels were measured, age-corrected to YKL-40 percentile values, and compared to HCs. Patients with myositis without interstitial lung disease were also enrolled and compared to HCs. Immunofluorescence staining was performed to identify YKL-40-positive inflammatory cells in muscle biopsy samples from two patients each with PM and DM. Age-corrected serum YKL-40 levels were significantly higher in patients with PM/DM compared to HCs with and without lung disease; however, these levels decreased significantly after treatment. Immunohistochemical analysis showed infiltration of YKL-40-positive inflammatory cells into the intramuscular sheath and perimuscular membrane. Immunofluorescence staining showed CD68 expression in YKL-40-positive inflammatory cells, suggesting that these cells were macrophages. To the best of our knowledge, this is the first study to demonstrate that YKL-40-positive macrophages are present in PM and DM, indicating that YKL-40 may be involved in PM/DM.

Loquat fruit rot, caused by Pestalotiopsis sensu lato, is a key problem for loquat producers in Nagasaki Prefecture, the area with the highest loquat fruit production in Japan. In a previous study, it was postulated that fruit rot pathogens latently infect flowers, with the corresponding disease symptoms occurring in wounded fruits. To reveal whether the pathogens responsible for the development of fruit rot disease are found in the asymptomatic flowers and immature fruits of loquat trees, we sprayed a conidial suspension of nitrate-nonutilizing mutants, containing strains derived from pathogenic Neopestalotiopsis sp. (TAP18N004) and Pestalotiopsis sp. (TAP18N010), onto the flowers of “Mogi” and “Nagasaki-wase” trees. Both inoculated mutants were reisolated using selective media (minimal media with chlorate) from the part of the asymptomatic immature fruit that includes the flower apex. Symptoms were observed in the mature fruits of both cultivars, and mutants were specifically detected in the symptomatic tissues of all rotted fruits. Additionally, all reisolated mutants were reconfirmed by assessing corresponding nitrate auxotrophy characteristics. Thus, it was revealed that both fruit rot pathogens that latently infect loquat flowers can cause fruit rot after maturation. [Figure: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.

Abstract Background and Aim Following treatment of superficial esophageal squamous cell carcinoma (ESCC), surveillance for a second primary malignancy (SPM) is necessary. However, detailed evidence regarding the timing and prognosis of SPMs is insufficient. We aimed to clarify the details of SPMs and their effects on patient outcomes. Methods This retrospective, multicenter study involved 11 hospitals. Patients with superficial ESCC curatively resected using endoscopic submucosal dissection between May 2005 and December 2012, were included in this study. Results The 5‐year survival rate of 187 patients was 92.6% during a median follow‐up duration of 96.8 months. Thirty‐one patients died, 14 of whom died of SPMs. Compared to patients with SPMs detectable by esophagogastroduodenoscopy (EGD), patients with SPMs detectable only by modalities other than EGD had a significantly higher mortality rate (p

Summary: The genetic mechanisms of reproductive isolation have been widely investigated within Asian cultivated rice (Oryza sativa); however, relevant genes between diverged species have been in sighted rather less. Herein, a gene showing selfish behavior was discovered in hybrids between the distantly related rice species Oryza longistaminata and O. sativa. The selfish allele S13l in the S13 locus impaired male fertility, discriminately eliminating pollens containing the allele S13s from O. sativa in heterozygotes (S13s/S13l). Genetic analysis revealed that a gene encoding a chromatin-remodeling factor (CHR) is involved in this phenomenon and a variety of O. sativa owns the truncated gene OsCHR745, whereas its homologue OlCHR has a complete structure in O. longistaminata. CRISPR-Cas9-mediated loss of function mutants restored fertility in hybrids. African cultivated rice, which naturally lacks the OlCHR homologue, is compatible with both S13s and S13l carriers. These results suggest that OlCHR is a Killer gene, which leads to reproductive isolation.

Uptake of thiosulfate ions as an inorganic sulfur source from the environment is important for bacterial sulfur assimilation. Recently, a selective thiosulfate uptake pathway involving a membrane protein YeeE (TsuA) in Escherichia coli was characterized. YeeE-like proteins are conserved in some bacteria, archaea, and eukaryotes. However, the precise function of YeeE, along with its potential partner protein in the thiosulfate ion uptake pathway, remained unclear. Here, we assessed selective thiosulfate transport via Spirochaeta thermophila YeeE in vitro and characterized E. coli YeeD (TsuB) as an adjacent and essential protein for YeeE-mediated thiosulfate uptake in vivo. We further showed that S. thermophila YeeD possesses thiosulfate decomposition activity and that a conserved cysteine in YeeD was modified to several forms in the presence of thiosulfate. Finally, the crystal structures of S. thermophila YeeE-YeeD fusion proteins at 3.34-Å and 2.60-Å resolutions revealed their interactions. The association was evaluated by a binding assay using purified S. thermophila YeeE and YeeD. Based on these results, a model of the sophisticated uptake of thiosulfate ions by YeeE and YeeD is proposed.

Abstract Background and aim Various techniques for direct biopsy from gastrointestinal subepithelial tumors (SETs) have been reported, although no standard method has been established. A common feature of these techniques is the removal of overlaying mucosa to enable direct biopsies from the SETs. These methods have been synthesized under the collective term “unroofing technique”. We conducted a multicenter retrospective study to assess its efficacy and identify potential complications. Methods This study was conducted in 10 hospitals and involved all eligible patients who underwent unroofing techniques to obtain biopsies for gastrointestinal SETs between April 2015 and March 2021. The primary endpoint was the diagnostic accuracy of the unroofing technique, and the secondary endpoints were the incidence of adverse events and the factors contributing to the accurate diagnosis. Results The study included 61 patients with 61 gastrointestinal SETs. The median tumor size was 20 mm, and the median procedure time was 38 min, with 82% successful tumor exposure. The rate of pathological diagnosis was 72.1%. In 44 patients with a pathological diagnosis, two showed discrepancies with the postresection pathological diagnosis. No factors, including facility experience, organ, tumor size, or tumor exposure, significantly affected the diagnostic accuracy. There was one case of delayed bleeding and two cases of perforation. Conclusion The diagnostic yield of the unroofing technique was acceptable. The unroofing technique was beneficial regardless of institutional experience, organ, tumor size, or actual tumor exposure.

Abstract The use of left ventricular assist device (LVAD) implantation has increased in recent years. Here, we report the first case of gastric endoscopic submucosal dissection (ESD) following LVAD implantation. A 69‐year‐old man who previously underwent LVAD implantation for severe heart failure underwent esophagogastroduodenoscopy, which revealed a 15‐mm flat‐elevated cancerous lesion at the greater curvature of the gastric angle. Before ESD, antithrombotic drugs were discontinued and replaced with 10,000 units of heparin. However, on the second day, the patient experienced dysarthria and right upper‐extremity movement disorder despite a prothrombin time/international normalized ratio (PT‐INR) of 2.01. On the fifth day, computed tomography revealed a low‐density area extending from the left corona radiata to the basal ganglia, leading to a diagnosis of acute cerebral infarction. Aspirin and warfarin were immediately restarted, while the heparin infusion was discontinued after confirming recovery of PT activity. Thereafter, the neurological abnormalities did not aggravate and a trend toward symptomatic improvement was observed. Two months later, ESD was performed under continuous warfarin administration (PT‐INR, 2.62) without heparin replacement, and the lesion was curatively resected without complications. The patient was discharged without adverse events. This case report provides useful information on the feasibility and perioperative management of ESD in patients with LVAD.

Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory dermatosis characterized by follicular, hyperkeratotic papules and palmoplantar keratoderma at any age. The exact etiology of the disease remains unknown, but it can be triggered by multiple factors and genetic backgrounds. Here, we describe a case of PRP occurring after SARS‐CoV‐2 vaccination. While the vaccination is generally safe, it should be kept in mind that PRP may be evoked by SARS‐CoV‐2 vaccination for early recognition of the cause and prognosis of the patients.

Abstract Background Autophagy plays an important role in carcinogenesis and tumor progression in many cancers, including gastric cancer. Cytotoxin-associated gene A (CagA) is a well-known virulent factor in Helicobacter pylori (H. pylori) infection that plays a critical role in gastric inflammation and gastric cancer development. However, its role in autophagy during these processes remains unclear. Therefore, we aimed to clarify the role of CagA in autophagy in CagA-related inflammation. Methods We evaluated the autophagic index of AGS cells infected with wild-type cagA-positive H. pylori (Hp-WT) and cagA-knockout H. pylori (Hp-ΔcagA) and rat gastric mucosal (RGM1) cells transfected with CagA genes. To identify the mechanisms underlying the down regulation of autophagy in AGS cells infected with H. pylori, we evaluated protein and mRNA expression levels of autophagy core proteins using western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR). To determine whether autophagy induced the expression of the pro-inflammatory mediator, cyclooxygenase-2 (COX-2), we evaluated COX-2 expression in AGS cells treated with an autophagy inducer and inhibitor and infected with H. pylori. In addition, we evaluated whether COX-2 protein expression in AGS cells influenced beclin-1 (BECN1) expression with si-RNA transfection when infected with H. pylori. Results Autophagic flux assay using chloroquine showed that autophagy in AGS cells was significantly suppressed after H. pylori infection. The autophagic index of AGS cells infected with Hp-WT was decreased significantly when compared with that in AGS cells infected with Hp-ΔcagA. The autophagic index of RGM1 cells transfected with CagA was lower, suggesting that CagA inhibits autophagy. In addition, BECN1 expression levels in AGS cells infected with Hp-WT were reduced compared to those in AGS cells infected with Hp-ΔcagA. Furthermore, COX-2 expression in AGS cells infected with H. pylori was controlled in an autophagy-dependent manner. When AGS cells were transfected with small interfering RNA specific for BECN1 and infected with Hp-WT and Hp-ΔcagA, COX-2 was upregulated significantly in cells infected with Hp-ΔcagA. Conclusions In conclusion, the H. pylori CagA protein negatively regulated autophagy by downregulating BECN1. CagA-induced autophagy inhibition may be a causative factor in promoting pro-inflammatory mediator production in human gastric epithelial cells.

Conventional rodent neuromyelitis optica spectrum disorder (NMOSD) models using patient-derived immunoglobulin G (IgG) are potentially affected by the differences between the human and rodent aquaporin-4 (AQP4) extracellular domains (ECDs). We hypothesized that the humanization of AQP4 ECDs would make the rodent model lesions closer to human NMOSD pathology. Humanized-AQP4-expressing (hAQP4) rats were generated using genome-editing technology, and the human AQP4-specific monoclonal antibody (mAb) or six patient-derived IgGs were introduced intraperitoneally into hAQP4 rats and wild-type Lewis (WT) rats after immunization with myelin basic protein and complete Freund’s adjuvant. Human AQP4-specific mAb induced astrocyte loss lesions specifically in hAQP4 rats. The patient-derived IgGs also induced NMOSD-like tissue-destructive lesions with AQP4 loss, demyelination, axonal swelling, complement deposition, and marked neutrophil and macrophage/microglia infiltration in hAQP4 rats; however, the difference in AQP4 loss lesion size and infiltrating cells was not significant between hAQP4 and WT rats. The patient-derived IgGs bound to both human and rat AQP4 M23, suggesting their binding to the shared region of human and rat AQP4 ECDs. Anti-AQP4 titers positively correlated with AQP4 loss lesion size and neutrophil and macrophage/microglia infiltration. Considering that patient-derived IgGs vary in binding sites and affinities and some of them may not bind to rodent AQP4, our hAQP4 rat is expected to reproduce NMOSD-like pathology more accurately than WT rats.

Objectives: The mitochondrial DNA (mtDNA) is unique and circular with multiple copies of the genome. The lower mtDNA copy number (mtDNA-CN) in leukocytes is associated with the risk of all-cause mortality. However, its long-term association is unknown. Thus, the study examined the association between mtDNA-CN and the risk of all-cause mortality in a long-term follow-up study in the Japanese population. Design: This longitudinal study included the study cohort from an annual, population-based health checkup in the town of Yakumo, Hokkaido, Japan. Setting and Participants: 814 participants (baseline age range: 38–80 years, mean: 56.3 years) were included in this study in 1990. They were followed-up regarding mortality for about 30 years (median: 28.1 years) till 2019. Measures: The genomic DNA was extracted from peripheral blood mononuclear cells and the mtDNA-CN was measured using real-time polymerase chain reaction. The level of the mtDNA-CN was divided into tertiles (low, middle, and high). The participants were categorized based on their age into middle-aged (

We report the discovery of two quasars at a redshift of z = 6.05 in the process of merging. They were serendipitously discovered from the deep multiband imaging data collected by the Hyper Suprime-Cam (HSC) Subaru Strategic Program survey. The quasars, HSC J121503.42−014858.7 (C1) and HSC J121503.55−014859.3 (C2), both have luminous (>10 ^43 erg s ^−1 ) Ly α emission with a clear broad component (full width at half maximum >1000 km s ^−1 ). The rest-frame ultraviolet (UV) absolute magnitudes are M _1450 = − 23.106 ± 0.017 (C1) and −22.662 ± 0.024 (C2). Our crude estimates of the black hole masses provide $\mathrm{log}({M}_{\mathrm{BH}}/{M}_{\odot })=8.1\pm 0.3$ in both sources. The two quasars are separated by 12 kpc in projected proper distance, bridged by a structure in the rest-UV light suggesting that they are undergoing a merger. This pair is one of the most distant merging quasars reported to date, providing crucial insight into galaxy and black hole build-up in the hierarchical structure formation scenario. A companion paper will present the gas and dust properties captured by Atacama Large Millimeter/submillimeter Array observations, which provide additional evidence for and detailed measurements of the merger, and also demonstrate that the two sources are not gravitationally lensed images of a single quasar.

T2 relaxation time in magnetic resonance imaging (MRI), which is determined by magnetic dipole interactions, has been employed as a parameter for tumor detection. However, owing to the lack of MRI detection sensitivity, nuclear medicine imaging is currently the basic option for tracking low concentrations of chemical probes. Previous studies utilizing cascade radionuclides have focused on the relaxation due to electric quadrupole interactions. However, magnetic dipole interactions, which are crucial in MRI, remains to be elucidated. In this study, we determined the magnetic relaxation rate by using 111In, a cascade radionuclide used in clinical single-photon emission computed tomography (SPECT) scans. As the angle between the gamma rays from the nuclei is affected by the electrical and magnetic interactions acting on the nuclei, we measured the angular correlation ratio by using eight gadolinium gallium garnet (GAGG) multi-pixel photon counter (MPPC) 8 × 8 array detectors and extracted the magnetic relaxation rate. Consequently, we obtained a rate that increased with the Fe concentration, similar to the T2 relaxation rate, although it was influenced by the inhomogeneity of the external magnetic field. This study utilized low concentrations of the liquid-state radionuclide, which is commonly used in clinical nuclear medicine imaging scans and is expected to provide much higher sensitivity and more selective detection of tumors than conventional MRI.

Introduction: Patients with nonidiopathic scoliosis often have a high risk associated with general anesthesia because of cardiac or pulmonary dysfunction secondary to underlying diseases. Base excess has been reported as a predictor in the management of trauma and cancer, although not yet in scoliosis. This study was performed to clarify the surgical outcomes and the association of perioperative complications with base excess in patients with nonidiopathic scoliosis who have a high risk associated with general anesthesia. Methods: Patients with nonidiopathic scoliosis who were referred to our institution from 2009 to 2020 because of their high risk associated with general anesthesia were retrospectively enrolled. High-risk factors for anesthesia were determined by a senior anesthesiologist and categorized into circulatory or pulmonary dysfunction. Perioperative complications were analyzed using the Clavien-Dindo classification; severe complications were defined as grade III. We investigated high-risk factors for anesthesia, underlying diseases, preoperative and postoperative Cobb angle, surgery-related factors, base excess, and postoperative management. These variables were statistically compared between patients with and without complications. Results: Thirty-six patients (mean age, 17.9 years old; range, 11-40 years old) were enrolled (two patients declined surgery). High-risk factors were circulatory dysfunction in 16 patients and pulmonary dysfunction in 20 patients. The mean Cobb angle improved from 85.1° (36°-128°) preoperatively to 43.6° (9°-83°) postoperatively. Three intraoperative complications and 23 postoperative complications occurred in 20 (55.6%) patients. Severe complications occurred in 10 (27.8%) patients. All patients underwent postoperative intensive care unit management after posterior all-screw construction. A large preoperative Cobb angle (p=0.021) and base excess outliers (>3 or 3 or

Abstract White blood cell (WBC) count profiles in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are still unknown. This study evaluated the total WBC count, differential WBC counts, monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with these diseases within three months from an attack before acute treatment or relapse prevention and compared the profiles with those in matched volunteers or in multiple sclerosis (MS) patients. AQP4-NMOSD patients (n = 13) had a higher neutrophil count (p = 0.0247), monocyte count (p = 0.0359), MLR (p = 0.0004), and NLR (p = 0.0037) and lower eosinophil (p = 0.0111) and basophil (p = 0.0283) counts than those of AQP4-NMOSD-matched volunteers (n = 65). Moreover, patients with MOGAD (n = 26) had a higher overall WBC count (p = 0.0001), neutrophil count (p

Objective: We evaluated whether the blood parameters before prostate biopsy can diagnose prostate cancer (PCa) and clinically significant PCa (Gleason score [GS] ≥7) in our hospital. Methods: This study included patients with increased prostate-specific antigen (PSA) up to 20 ng/mL. The associations of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) alone or with PSA with PCa and clinically significant PCa were analyzed. Results: We included 365 patients, of whom 52.9% (193) had PCa including 66.8% (129) with GS of ≥7. PSA density (PSAD) and PSA had better the area under the curve (AUC) of 0.722 and 0.585, respectively with p=0.001 for detecting PCa compared with other blood parameters. PSA combined with PLR (PsPLR) and PSA with NLR (PsNLR) had better AUC of 0.608 and 0.610, respectively with p

Background and Objectives: Changes in activities of daily living (ADL) and quality of life (QOL) of patients with bone metastasis who underwent surgical treatment through Bone Metastasis Cancer Boards (BMCBs), a recent multidisciplinary approach for managing bone metastases, have been reported; however, no reports exist on patients who undergo conservative treatment. In this study, we aimed to evaluate these patients’ ADL and QOL and examine the factors influencing changes in these parameters. Materials and Methods: We retrospectively reviewed 200 patients with bone metastases who underwent conservative therapy through BMCBs between 2013 and 2021. A reassessment was conducted within 2–8 weeks after the initial assessment. Patients’ background and changes in performance status (PS), Barthel Index (BI), EuroQol five-dimension (EQ-5D) scores, and Numerical Rating Scale (NRS) scores were initially assessed. Furthermore, we categorized patients into two groups based on improvements or deteriorations in ADL and QOL and performed comparative analyses. Results: Significant improvements in EQ-5D (0.57 ± 0.02 versus [vs.] 0.64 ± 0.02), NRS max (5.21 ± 0.24 vs. 3.56 ± 0.21), and NRS average (2.98 ± 0.18 vs. 1.85 ± 0.13) scores were observed between the initial assessment and reassessment (all p < 0.001). PS (1.84 ± 0.08 vs. 1.72 ± 0.08) and BI (83.15 ± 1.68 vs. 84.42 ± 1.73) also showed improvements (p = 0.06, and 0.054, respectively). In addition, spinal cord paralysis (odds ratio [OR]: 3.69, p = 0.049; OR: 8.42, p < 0.001), chemotherapy (OR: 0.43, p = 0.02; OR: 0.25, p = 0.007), and NRS average scores (OR: 0.38, p = 0.02; OR: 0.14, p < 0.001) were independent factors associated with ADL and QOL. Conclusions: Patients with bone metastases who underwent conservative treatment through BMCBs exhibited an increase in QOL without a decline in ADL. The presence of spinal cord paralysis, absence of chemotherapy, and poor pain control were associated with a higher risk of deterioration in ADL and QOL.

Similar to cacao pod rot, cherelle wilt decreases production from cacao fields. Among all known fungal pathogens of the cacao, Colletotrichum spp. are common infectious agents that affect the cherelles and pods of cacao; thus, cacao diseases are often classified by stage. Therefore, knowing whether these pathogens are common in both fruit stages is necessary for implementing disease control measures. Symptoms of cherelle wilt were found in cacao plants in Pangasinan, Philippines, in 2022. The fungal strain obtained from the lesion was found to be pathogenic towards cherelles, but not towards pods. The strain was classified as an unknown species belonging to the gigasporum species complex, based on the morphological and molecular phylogenetic analyses of ITS, GAPDH, CHS1, ACT, and TUB2. We propose Colletotrichum kapreanum sp. nov. as a causal agent of cacao cherelle wilt, but not pod rot.

IntroductionGut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD. MethodsFecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2.ResultsFor alpha diversity, Faith’s phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray–Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini–Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of Ruminococcus gnavus group and lower relative abundance of Blautia. Discussion and conclusionRuminococcus gnavus group reportedly includes pro-inflammatory bacteria. In contrast, Blautia suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of Blautia in parallel with increased abundance of Ruminococcus gnavus group might be a susceptibility factor for KD.

Aims: We investigated imaging dose and noise under clinical scan conditions at multiple institutions using a simple and unified method, and demonstrated the need for diagnostic reference levels in image-guided radiotherapy (IGRT). Materials and Methods: Nine cone-beam and helical computed tomography (CT) scanners (Varian, Elekta, Accuray Inc., and BrainLAB) from seven institutions were investigated in this study. The weighted cone-beam dose index (CBDIw) was calculated for head and pelvic protocols using a 100 mm pencil chamber under the conditions used in actual clinical practice at each institution. Cone-beam CT image noise was evaluated using polymethylmethacrylate head and body phantoms with diameters of 16 and 32 cm, respectively. Results: For head and pelvic protocols, CBDIw values ranged from 0.94–6.59 and 1.47–20.9 mGy, respectively. Similarly, standard deviation (SD) values ranged from 9.3–34.0 and 26.9–97.4 HU, respectively. The SD values tended to increase with decreasing imaging dose (r = −0.33 and −0.61 for the head and pelvic protocols, respectively). Conclusions: Among the nine machines, the imaging dose for high imaging dose institutions was approximately 20 mGy to the pelvic phantom, and there was a 14-fold difference in dose compared with the other institutions. These results suggest the need to establish DRLs for IGRT to guide clinical decision-making.

Abstract Background No reports have been published about participation in sports activity and subjective health status after total hip arthroplasty via the anterolateral approach in the supine position (ALS-THA) in Japanese patients. This study assessed sports activity participation and subjective health status, as well as factors potential associated with these variables, in patients who underwent ALS-THA. Methods Of 698 patients who underwent total hip arthroplasty at our institution between 2013 and 2018, questionnaires were sent to 355 patients under 80 years old who had undergone ALS-THA and 242 responded. Patients were asked about their subjective health status, participation in sports activity, the EuroQol 5-dimensions 5-level (EQ-5D-5L), the University of California Los Angeles (UCLA) activity scale score and the Forgotten Joint Score (FJS). Patient characteristics and hospitalization information were also collected. Patients’ subjective health status was categorized as “healthy” or “unhealthy”. Univariate and multivariate logistic regression analyses were performed to determine factors associated with participation in sports activity after ALS-THA and a “healthy” status. Results The pre- and postoperative sports activity participation rates were 54.0% and 57.8%, respectively. Most patients (76.8%, n = 182) were considered “healthy”. Age (P = .019) and UCLA activity score (P

Carbon-ion radiotherapy (CIRT) for prostate cancer is both safe and efficacious; beam range calculations use relative stopping power ratio, which is derived from computed tomography (CT) values. However, hip prostheses are made of high atomic number materials and show severe artifacts on CT images. Therefore, it is not possible to accurately calculate dose distribution for CIRT in patients with prostate cancer with hip prostheses. Here, we describe the management of a 77-year-old man with prostate cancer who had previously undergone bilateral hip replacement. CIRT, in combination with androgen deprivation therapy, was recommended as definitive treatment for prostate cancer. Planning CT, magnetic resonance (MRI), and CT images with metal artifact reduction (MAR) were acquired for CIRT planning. MRI and MAR images were superimposed on the planning CT to delineate target volume and organs at risk. The radiation treatment plan consisted of a total dose of 51.6 Gy (relative biological effect) to be delivered in 12 fractions over 3 weeks, and the patient was irradiated in the supine and prone positions with a vertical beam, on alternating days. CIRT was completed as scheduled. No adverse events were observed during treatment or at 3 months after treatment initiation. While we show that CIRT may be a treatment option for patients with prostate cancer with bilateral hip prostheses, further studies are needed to evaluate treatment efficacy and late toxicity and to determine how CIRT can be administered to patients with prostate cancer with bilateral hip prostheses.