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Tectal glioma (TG) is a rare lower grade glioma (LrGG) that occurs in the tectum, mainly affecting children. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. We conducted a retrospective review of cases clinically diagnosed as TG and treated at our institute between January 2005 and March 2023. Six cases were identified and the median age was 30.5 years. Four patients underwent biopsy and two patients underwent tumor resection. Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. The integrated diagnosis, according to the fifth edition of the World Health Organization Classification of Tumours of the central nervous system, included two cases of PA and one case each of diffuse high-grade glioma; diffuse midline glioma H3 K27-altered; glioblastoma; and circumscribed astrocytic glioma. Among the three patients who underwent molecular evaluation, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation., (© 2024. The Author(s).)

The digestion behavior of a food bolus comprising bread particles in the presence of gastric peristalsis remains poorly understood. This study systematically investigated the effect of bread type on in vitro gastric digestion behavior using a human gastric digestion simulator (GDS) that is capable of quantitatively simulating gastric peristalsis. A food bolus consisting of 60 g of bread (white bread, bagel, German bread, French bread, or croissant), 15 mL of a simulated salivary fluid, and 240 mL of a simulated gastric fluid was used for gastric digestion in vitro using the GDS for 3 h at 37 °C. Direct observation of the gastric digestion behavior in the GDS vessel demonstrated that the structure and composition of breads considerably influenced the physical digestion processes of bread particles. These processes include their fracture, rubbing, disintegration, swelling owing to the penetration of gastric fluid, and release of fat from their surface. Fluorescence microscopy enabled an improved understanding of the variations in the microstructure and major component distribution of the breads during the gastric digestion in vitro. The results showed how the different breads influenced gastric digestibility in vitro through quantitative gastric peristalsis. The GDS can also be applicable to studying gastric digestibility in vitro of other types of bread.

Dynamin is a microtubule (MT) binding protein playing a key role in vesicle endocytosis. In a brain slice model, tau loaded in presynaptic terminals assembles MTs, thereby impairing vesicle endocytosis via depletion of cytosolic dynamin. The peptide PHDP5, derived from the pleckstrin homology domain of dynamin 1, inhibits dynamin-MT interaction and rescues endocytosis and synaptic transmission impaired by tau when co-loaded in presynaptic terminals. We tested whether in vivo administration of PHDP5 could rescue the learning/memory deficits observed in Alzheimer's disease (AD) model mice. A modified PHDP5 incorporating a cell-penetrating peptide (CPP) and a FITC fluorescent marker was delivered intranasally to Tau609 transgenic (Tg) and 3xTg-AD mice. FITC-positive puncta were observed in the hippocampus of mice infused with PHDP5 or scrambled (SPHDP5) peptide, but not in saline-infused controls. In the Morris water maze (MWM) test for spatial learning/memory, AD model mice treated with FITC-PHDP5-CPP showed prominent improvements in learning and memory, performing close to the level of saline-infused WT mice control. In contrast, mice treated with a scrambled construct (FITC-SPHDP5-CPP) showed no significant improvement. We conclude that PHDP5 can be a candidate for human AD therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Recent studies indicate that 123I-iomazenil (123I-IMZ) single-photon emission computed tomography (SPECT) can demonstrate neuronal viability. Although cognitive dysfunction has been recognized as an important issue in adult patients with moyamoya disease (MMD), no standard neuroradiological methods to define such conditions have been established. We examined the relationship between cognitive function and 123I-IMZ SPECT before and after revascularization in patients with MMD., Methods: The study participants were 16 adult patients with MMD whose cerebrovascular reactivities were decreased only on the surgical sides of combined revascularization. Cognitive function was examined using the Mini-Mental State Examination (MMSE; cutoff: 27) and the Frontal Assessment Battery (FAB; cutoff: 16) before and at 3 to 6 months after surgery. 123I-iodoamphetamine (123I-IMP) SPECT with acetazolamide challenge and 123I-IMZ SPECT were performed concurrently while evaluating cognitive function. The radioreactivities of 123I-IMZ SPECT in regions with decreased cerebrovascular reactivities on 123I-IMP SPECT were investigated using affected-to-contralateral side asymmetry ratio (IMZ-ACR)., Results: Twelve patients showed normal cognitive function (MMSE: 29.8 ± 0.4, FAB: 18 ± 0) before surgery. No evident laterality of 123I-IMZ uptake was seen (IMZ-ACR: 0.98 ± 0.04). Neither cognitive function nor 123I-IMZ SPECT worsened after surgery (MMSE: 29.8 ± 0.3, FAB: 18 ± 0, IMZ-ACR: 1.00 ± 0.04). By contrast, 4 patients presented cognitive dysfunction (MMSE: 24.3 ± 3.9, FAB: 14.8 ± 2.7) before revascularization. Preoperative imaging of these patients showed decreased 123I-IMZ uptake, and their IMZ-ACRs (0.83 ± 0.08) were significantly lower than those of the normal group. After revascularization, cognitive functions and 123I-IMZ uptake tended to ameliorate (MMSE: 27.5 ± 1.7, FAB: 16.3 ± 2.2, IMZ-ACR: 0.94 ± 0.09)., Conclusion: Preoperative cognitive function was associated with 123I-IMZ uptake in adult patients with MMD. After revascularization, cognitive function could be recovered in the viable areas of the brain, which is consistent with 123I-IMZ SPECT findings., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Possible local influence of an extreme marine heatwave is investigated on unprecedentedly hot summer around northern Japan in 2023. Sea-surface temperatures (SSTs) and subsurface ocean temperatures around northern Japan were also unprecedentedly high in the summer. This was especially the case off the east coast of Japan, where cool Oyashio water was replaced with much warmer water due to a striking poleward meander of the Kuroshio Extension persistent from the spring. Particularly amplified near-surface air temperature anomalies and even stronger warm anomalies in the subsurface ocean suggest that the marine heatwave acted to sustain the atmospheric heatwave. Anomalous upward of latent and sensible heat fluxes from the warmed sea surface are indicative of local oceanic impact. The warm SST anomalies reduced the lower-tropospheric stratification to maintain unfavourable condition for low-level cloud formation, which in turn led to increased surface insolation for further SST warming as positive feedback. The increased moisture in the warmed lower troposphere contributed to the enhanced surface downward longwave radiation. This enhanced greenhouse effect acted not only as positive feedback on the warm SST anomalies that increased evaporation but also as a contributor for the extreme warmth over northern Japan landmass., (© 2024. The Author(s).)

Objective: Radium-223 is a first alpha-emitting radionuclide treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases. Although the spread-based bone scan index (BSI) and novel index of the intensity-based two-dimensional total bone uptake (2D-TBU) from bone scintigraphy may provide useful input in radium-223 treatment, they have not been evaluated in detail yet. This study aimed to fill this gap by evaluating BSI and 2D-TBU in patients treated with radium-223., Methods: Twenty-seven Japanese patients with mCRPC treated with radium-223 were retrospectively analyzed. The patients were evaluated via blood tests and bone scans at baseline and 3 cycles intervals of treatment. BSI and 2D-TBU were analyzed via VSBONE BSI in terms of correlations, response to radium-223 treatment, association with treatment completion, and the Kaplan-Meier survival analysis was performed., Results: Nineteen patients (70.4%) completed six cycles of radium-223 treatment, whereas eight patients (29.6%) did not complete the treatment regimen. A significant difference in baseline BSI and 2D-TBU was observed between these groups of patients. Both BSI and 2D-TBU were highly correlated (r = 0.96, p < 0.001). Univariate analysis showed an association between radium-223 completion in median BSI and 2D-TBU values (p = 0.015) and completion percentage differences (91.7% vs. 45.5%; p = 0.027). The Kaplan-Meier product limit estimator showed that the median overall survival was 25.2 months (95% CI 14.0-33.6 months) in the completion group and 7.5 months (95% CI 3.3-14.2 months) in the without completion group (p < 0.001). The overall survival based on median cutoff levels showed a significant difference in 2D-TBU (p = 0.007), but not in BSI (p = 0.15)., Conclusions: The 2D-TBU may offer advantages over BSI in classifying patients towards radium-223 treatment based on the degree of progression of bone metastases. This study supports the importance of preliminary assessment of bone metastasis status using BSI and 2D-TBU extracted from VSBONE BSI for radium-223 treatment decisions., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

The rhizomes of Acorus tatarinowii Schott and Acorus gramineus Solander are widely used for treating amnesia in traditional Chinese medicine. In contrast, their leaves are usually discarded without their medicinal properties being known. Here, we found that the hot water extract of leaves improved cognition and tau pathology in model mice of frontotemporal dementia, similar to or even better than that of rhizomes. To explore the optimal method of processing, we made three preparations from dried leaves: hot water extract, extraction residue, and non-extracted simple crush powder. Among them, the simple crush powder had the strongest effect on tauopathy in mice. The crush powder also ameliorated Aβ and α-synuclein pathologies and restored cognition in mouse models of Alzheimer's disease and dementia with Lewy bodies. These findings suggest the potential of Acorus tatarinowii / gramineus leaves as a dietary source for dementia prevention and reveal that simple crushing is a better way to maximize their efficacy.

Background: Previous studies have explored the association between the number of cases and patient outcomes for critical illnesses such as sepsis and trauma, as well as various surgeries, with the expectation that a higher number of cases would have a more favorable effect on patient outcomes. The aim of this study was to elucidate the association among intensive care unit (ICU) case volume, specialization, and patient outcomes in critically ill emergency patients and to determine how ICU case volumes and specializations impact the outcomes of these patients in Japanese ICUs., Methods: Utilizing data from the Japanese Intensive Care PAtient Database (JIPAD) from April 2015 to March 2021, this retrospective cohort study was conducted in 80 ICUs across Japan and included 72,214 emergency patients aged ≥ 16 years. The primary outcome measure was in-hospital mortality, and the secondary outcomes encompassed ICU mortality, 28-day mortality, ventilator-free days, and the lengths of ICU and hospital stays. Bayesian hierarchical generalized linear mixed models were used to adjust for patient- and ICU-level variables., Results: This study revealed a significant association between a higher ICU case volume and decreased in-hospital mortality. In particular, ICUs with a higher percentage (> 75%) of emergency patients showed more pronounced effects, with the odds ratios for in-hospital mortality in the higher case volume quartiles (Q2, Q3, and Q4) being 0.92 (95% credible interval [CI]: 0.88-0.96), 0.70 (95% CI: 0.67-0.73), and 0.78 (95% CI: 0.73-0.83), respectively, compared with the lowest quartile (Q1). Similar trends were observed for various secondary outcomes., Conclusions: Higher ICU case volumes were significantly associated with lower in-hospital mortality rates in Japanese ICUs predominantly treating critically ill emergency patients. These findings emphasize the importance of ICU specialization and highlight the potential benefits of centralized care for critically ill emergency patients. These findings are potential insights for improving health care policy in Japan and may be valuable in emergency care settings in other countries with similar healthcare systems, after careful consideration of contextual differences., (© 2024. The Author(s).)

The majority of low-grade isocitrate dehydrogenase-mutant (IDH mt ) gliomas undergo malignant progression (MP), but their underlying mechanism remains unclear. IDH mt gliomas exhibit global DNA methylation, and our previous report suggested that MP could be partly attributed to passive demethylation caused by accelerated cell cycles. However, during MP, there is also active demethylation mediated by ten-eleven translocation, such as DNA hydroxymethylation. Hydroxymethylation is reported to potentially contribute to gene expression regulation, but its role in MP remains under investigation. Therefore, we conducted a comprehensive analysis of hydroxymethylation during MP of IDH mt astrocytoma. Five primary/malignantly progressed IDH mt astrocytoma pairs were analyzed with oxidative bisulfite and the Infinium EPIC methylation array, detecting 5-hydroxymethyl cytosine at over 850,000 locations for region-specific hydroxymethylation assessment. Notably, we observed significant sharing of hydroxymethylated genomic regions during MP across the samples. Hydroxymethylated CpGs were enriched in open sea and intergenic regions (p < 0.001), and genes undergoing hydroxymethylation were significantly associated with cancer-related signaling pathways. RNA sequencing data integration identified 91 genes with significant positive/negative hydroxymethylation-expression correlations. Functional analysis suggested that positively correlated genes are involved in cell-cycle promotion, while negatively correlated ones are associated with antineoplastic functions. Analyses of The Cancer Genome Atlas clinical data on glioma were in line with these findings. Motif-enrichment analysis suggested the potential involvement of the transcription factor KLF4 in hydroxymethylation-based gene regulation. Our findings shed light on the significance of region-specific DNA hydroxymethylation in glioma MP and suggest its potential role in cancer-related gene expression and IDH mt glioma malignancy., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Consumers are concerned about employing green processing technologies and natural ingredients in different manufacturing sectors to achieve a "clean label" standard for products and minimize the hazardous impact of chemical ingredients on human health and the environment. In this study, we investigated the effects of gelatinized starch dispersions (GSDs) prepared from six plant sources ( indica and japonica rice, wheat, corn, potatoes, and sweet potatoes) on the formulation and stability of oil-in-water (O/W) emulsions. The effect of gelatinization temperature and time conditions of 85-90 °C for 20 min on the interfacial tension of the two phases was observed. Emulsification was performed using a primary homogenization condition of 10,000 rpm for 5 min, followed by high-pressure homogenization at 100 MPa for five cycles. The effects of higher oil weight fractions (15-25% w / w ) and storage stability at different temperatures for four weeks were also evaluated. The interfacial tension of all starch GSDs with soybean oil decreased compared with the interfacial tension between soybean oil and water as a control. The largest interfacial tension reduction was observed for the GSD from indica rice. Microstructural analysis indicated that the GSDs stabilized the O/W emulsion by coating oil droplets. Emulsions formulated using a GSD from indica rice were stable during four weeks of storage with a volume mean diameter ( d 4,3 ) of ~1 µm, minimal viscosity change, and a negative ζ-potential.

Neurodegenerative diseases including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies are age-related disorders and the main cause of dementia. They are characterized by the cerebral accumulation of Aβ, tau, α-synuclein, and TDP-43. Because the accumulation begins decades before disease onset, treatment should be started in the preclinical stage. Such intervention would be long-lasting, and therefore, prophylactic agents should be safe, non-invasively taken by the patients, and inexpensive. In addition, the agents should be broadly effective against etiologic proteins and capable of repairing neurons damaged by toxic oligomers. These requirements are difficult to meet with single-ingredient pharmaceuticals but may be feasible by taking proper diets composed of multiple ingredients. As a source of such diets, we focused on the Hawaiian native herb Mamaki. From its dried leaves and fruits, we made three preparations: hot water extract of the leaves, non-extracted simple crush powder of the leaves, and simple crush powder of the fruits, and examined their effects on the cognitive function and neuropathologies in four different mouse models of neurodegenerative dementia. Hot water extract of the leaves attenuated neuropathologies, restored synaptophysin levels, suppressed microglial activation, and improved memory when orally administered for 1 month. Simply crushed leaf powder showed a higher efficacy, but simply crushed fruit powder displayed the strongest effects. Moreover, the fruit powder significantly enhanced the levels of brain-derived neurotrophic factor expression and neurogenesis, indicating its ability to repair neurons. These results suggest that crushed Mamaki leaves and fruits are promising sources of dementia-preventive diets., (© 2023. The Author(s), under exclusive licence to American Aging Association.)

This study explored the effectiveness of nasal administration in delivering magnetic nanoparticles into the brain for magnetic particle imaging of target regions. Successful delivery of iron oxide nanoparticles, which serve as contrast agents, to specific sites within the brain is crucial for achieving magnetic particle imaging. Nasal administration has gained attention as a method to bypass the blood-brain barrier and directly deliver therapeutics to the brain. In this study, we investigated surface modification techniques for administering magnetic nanoparticles into the nasal cavity, and provided experimental validation through in vivo studies. By compositing magnetic nanoparticles with gold nanoparticles, we enabled additional surface modification via AuS bonds without compromising their magnetic properties. The migration of the designed PEGylated magnetic nanoparticles into the brain following nasal administration was confirmed by magnetization measurements. Furthermore, we demonstrated the accumulation of these nanoparticles at specific target sites using probe molecules immobilized on the PEG terminus. Thus, the efficacy of delivering magnetic nanoparticles to the brain via nasal administration was demonstrated in this study. The findings of this research are expected to contribute significantly to the realization of magnetic particle imaging of target regions within the brain., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class "spinal ependymoma" (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities., (© 2024. The Author(s).)

This study aimed to analyze the printability of corn-based dough during screw-based three-dimensional (3D) food printing (3DFP) by relating its rheological and mechanical properties to its screw-based 3DFP performance, with the objective of providing insights into the utilization of corn-based dough to produce 3D-printed foods. Screw-based 3DFP was performed using seven corn-based doughs with different nixtamalized corn flour (NCF) and water contents. Afterward, their rheological and mechanical properties were analyzed and associated with their screw-based 3DFP performance. The results showed that stable printability was obtained within a specific range of NCF content in the dough (30-32.5 wt%). Below this range, the 3D-printed foods flattened, while above it, the extrudability of the dough was affected. The printability of the dough was influenced by different rheological and mechanical properties, depending on the stage of the screw-based 3DFP process. During the extrusion stage, the loss tangent at nozzle strain, yield stress, apparent viscosity, and adhesiveness mainly affected the extrudability of the dough. In contrast, the loss tangent at minimum strain, elastic modulus, Young's modulus, and hardness influenced the self-supporting stage. Therefore, it is important to find a balance between all of these properties, where stable extrudability and self-supporting of the 3D structure are achieved.

Since propionate exerts several physiological effects, maintenance of its normal colonic fermentation is essential. To investigate whether vitamin B 12 (VB 12 ) is essential for normal propionate fermentation by colonic bacteria, via the succinate pathway, we examined if high-amylose cornstarch (HACS) feeding activated such a pathway, if high HACS feeding impaired propionate fermentation, and if oral VB 12 supplementation normalized propionate fermentation. Male rats were given control, 20% HACS or 3% fucose diets (Expt. 1); a VB 12 -free control diet or one supplemented with 5-30% HACS (Expt. 2); and the 20% HACS diet supplemented with 0.025-25 mg/kg of VB 12 (Expt. 3), for 14 d. HACS feeding significantly increased cecal succinate concentration, activating the succinate pathway (Expt. 1). Cecal cobalamin concentration in 20% and 30% HACS groups was about 75% of that in the control group (Expt. 2). Cecal succinate and propionate concentrations significantly increased and decreased in 30% HACS groups, respectively, compared with the control group. Although HACS group supplemented with 0.025 mg/kg of VB 12 had a low concentration of cecal propionate, adding high amounts of VB 12 to HACS diets provided sufficient amounts of VB 12 to rat ceca and increased cecal propionate concentration (Expt. 3). Compared with the non-HACS group, the relative abundance of Akkermansia muciniphila, but not Bacteroides/Phocaeicola, was lower in the HACS counterpart and showed improvement with increased VB 12 doses. To summarize, feeding high HACS decreased and increased cecal VB 12 and succinate concentrations, respectively. Furthermore, colonic delivery of sufficient amounts of VB 12 to rats likely reduced accumulation of succinate and normalized propionate fermentation.

Potassium ferrate (K 2 FeO 4 ) containing hexavalent iron [Fe(VI)] is an environmentally friendly oxidant, which possesses strong oxidizing power to treat wastewater and sludge. Therefore, the present study investigated degradation of selected antibiotics, namely levofloxacin (LEV), ciprofloxacin (CIP), oxytetracycline (OTC), and azithromycin (AZI), in water and anaerobically digested sewage sludge samples using Fe(VI). The effects of different Fe(VI) concentrations and initial pH values on antibiotic removal efficiency were evaluated. Under the studied conditions, LEV and CIP were almost completely removed from water samples, following second-order kinetics. In addition, over 60% of the four selected antibiotics were removed from sludge samples using 1 g L -1 Fe(VI). Furthermore, P phytoavailability and compostability of Fe(VI)-treated sludge were evaluated using different extraction reagents and a small composting unit. The extraction efficiency of phytoavailable P using 2% citric acid and neutral ammonium citrate was approximately 40% and 70%, respectively. The mixture of Fe(VI)-treated sludge and rice husk was self-heated in a closed composting reactor through the biodegradation of organic matter derived from the treated sludge. Therefore, Fe(VI)-treated sludge may be used as an organic material containing phytoavailable P for compost., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: During the fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Japan, which took place between June and September 2021, a significant number of COVID-19 cases with deterioration occurred in unvaccinated individuals < 65 years old. However, the risk factors for COVID-19 deterioration in this specific population have not yet been determined. This study developed a prediction method to identify COVID-19 patients < 65 years old who are at a high risk of deterioration., Methods: This retrospective study analyzed data from 1,675 patients < 65 years old who were admitted to acute care institutions in Fukushima with mild-to-moderate-1 COVID-19 based on the Japanese disease severity criteria prior to the fifth wave. For validation, 324 similar patients were enrolled from 3 hospitals in Yamagata. Logistic regression analyses using cluster-robust variance estimation were used to determine predictors of disease deterioration, followed by creation of risk prediction scores. Disease deterioration was defined as the initiation of medication for COVID-19, oxygen inhalation, or mechanical ventilation starting one day or later after admission., Results: The patients whose condition deteriorated (8.6%) tended to be older, male, have histories of smoking, and have high body temperatures, low oxygen saturation values, and comorbidities, such as diabetes/obesity and hypertension. Stepwise variable selection using logistic regression to predict COVID-19 deterioration retained comorbidities of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). Two predictive scores were created based on the optimism-corrected regression coefficients: the DOATS score, including all of the above risk factors, and the DOAT score, which was the DOATS score without oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve (AUROCs) of the DOATS and DOAT scores were 0.81 (95% confidence interval [CI] 0.77-0.85) and 0.80 (95% CI 0.76-0.84), respectively. In the validation cohort, the AUROCs for each score were both 0.76 (95% CI 0.69-0.83), and the calibration slopes were both 0.80. A decision curve analysis confirmed the clinical practicability of both scores in the validation cohort., Conclusions: We established two prediction scores that can quickly evaluate the risk of COVID-19 deterioration in mild/moderate patients < 65 years old., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To estimate the ratio of menstrual abnormalities, infertility, and other problems related to pregnancy and childbirth in former long-distance runners. We hypothesized that the female athlete triad during an athletic career affects future fertility and childbearing in former athletes., Design: Cross-sectional study., Setting: Participants of the All Japan University Women's Ekiden., Participants: Female former athletes who competed at national level were asked to complete the questionnaire; 137 valid responses were obtained., Independent Variables: Age at menarche and at the onset of pregnancy, history of amenorrhea and gynecological disorders, and lowest body mass index (BMI) during their athletic career., Main Outcome Measures: Menstrual status, history of pregnancy and childbirth, any related infertility treatment and problems, and history of stress fractures., Results: The mean age at menarche was 13.3 ± 2.2 (range, 10-25) years. Five athletes (3.6%) had primary amenorrhea. Eleven of the 137 participants (8.0%) required treatment for infertility. Sixty participants had 121 pregnancies, of which 5 were yet to deliver during the survey. Fifteen of 116 pregnancies (12.9%) ended in miscarriage, induced abortion, or stillbirth. Logistic regression analysis showed that the factors related to "infertility treatment" were age at the onset of pregnancy ( P = 0.047) and higher BMI during their athletic career ( P = 0.032; odds ratio, 2.19)., Conclusions: The main factor influencing infertility was an older age at the time of pregnancy, similar to that observed in the general population. Amenorrhea or being underweight during their athletic career was not associated with problems related to conception and childbirth., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

A major challenge in human stroke research is interpatient variability in the extent of sensorimotor deficits and determining the time course of recovery following stroke. Although the relationship between the extent of the lesion and the degree of sensorimotor deficits is well established, the factors determining the speed of recovery remain uncertain. To test these experimentally, we created a cortical lesion over the motor cortex using a reproducible approach in four common marmosets, and characterized the time course of recovery by systematically applying several behavioral tests before and up to 8 weeks after creation of the lesion. Evaluation of in-cage behavior and reach-to-grasp movement revealed consistent motor impairments across the animals. In particular, performance in reaching and grasping movements continued to deteriorate until 4 weeks after creation of the lesion. We also found consistent time courses of recovery across animals for in-cage and grasping movements. For example, in all animals, the score for in-cage behaviors showed full recovery at 3 weeks after creation of the lesion, and the performance of grasping movement partially recovered from 4 to 8 weeks. In addition, we observed longer time courses of recovery for reaching movement, which may rely more on cortically initiated control in this species. These results suggest that different recovery speeds for each movement could be influenced by what extent the cortical control is required to properly execute each movement., 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 Kosugi, Saga, Kudo, Koizumi, Umeda and Seki.)

Introduction. The application of data-driven respiratory gating (DDG) for subcentimeter lesions with respiratory movement remains poorly understood. Hence, this study aimed to clarify DDG application for subcentimeter lesions and the ability of digital Positron emission tomography/computed tomography (PET/CT) system combined with DDG to detect these lesions under three-axis respiration. Methods. Discovery MI PET/CT system and National Electrical Manufacturers Association (NEMA) body phantom with Micro Hollow Sphere (4, 5, 6, 8, 10, and 13 mm) were used. The NEMA phantom was filled with 18 F-FDG solutions of 42.4 and 5.3 kBq/ml for each hot sphere and background region. The 3.6 s cycles of three-axis respiratory motion were reproduced using the motion platform UniTraQ. The PET data acquisition was performed in stationary and respiratory-moving states. The data were reconstructed in three PET groups: stationary (NM-PET), no gating with respiratory movement (NG-PET), and DDG gating with respiratory movement (DDG-PET) groups. For image quality, percent contrast (Q H ); maximum, peak, and mean standardized uptake value (SUV); background region; and detectability index (DI) were evaluated in each PET group. Visual assessment was also conducted. Results. The groups with respiratory movement had deteriorated Q H and SUVs compared with NM-PET. Compared with NG-PET, DDG-PET has significantly improved Q H and SUVs in spheres above 6 mm. The background region showed no significant difference between groups. The SUVmax, SUVpeak, and Q H values of 8 mm sphere were highest in NM-PET, followed by DDG-PET and NG-PET. In visual assessment, the spheres above 6 mm were detected in all PET groups. DDG application did not detect new lesions, but it increased DI and visual score. Conclusions . The application of principal component analysis (PCA)-based DDG algorithm improves both image quality and quantitative SUVs in subcentimeter lesions measuring above 6 mm. Although DDG application cannot detect new subcentimeter lesions, it increases the visual indices., (© 2022 IOP Publishing Ltd.)

Descending motor drive and somatosensory feedback play important roles in modulating muscle activity. Numerous studies have characterized the organization of neuronal connectivity in which descending motor pathways and somatosensory afferents converge on spinal motor neurons as a final common pathway. However, how inputs from these two pathways are integrated into spinal motor neurons to generate muscle activity during actual motor behavior is unknown. Here, we simultaneously recorded activity in the motor cortices (MCx), somatosensory afferent neurons, and forelimb muscles in monkeys performing reaching and grasping movements. We constructed a linear model to explain the instantaneous muscle activity using the activity of MCx (descending input) and peripheral afferents (afferent input). Decomposition of the reconstructed muscle activity into each subcomponent indicated that muscle activity before movement onset could first be explained by descending input from mainly the primary motor cortex and muscle activity after movement onset by both descending and afferent inputs. Descending input had a facilitative effect on all muscles, whereas afferent input had a facilitative or suppressive effect on each muscle. Such antagonistic effects of afferent input can be explained by reciprocal effects of the spinal reflex. These results suggest that descending input contributes to the initiation of limb movement, and this initial movement subsequently affects muscle activity via the spinal reflex in conjunction with the continuous descending input. Thus, spinal motor neurons are subjected to temporally organized modulation by direct activation through the descending pathway and the lagged action of the spinal reflex during voluntary limb movement.

Objective: Fractional exhaled nitric oxide (FeNO) is considered to be an adjunct for asthma management, although its usefulness remains controversial. Therefore, it may be necessary for new approaches to use FeNO for asthma management. We evaluated whether diurnal variations of FeNO can predict response to asthma treatment., Methods: This pilot study consisted of 22 uncontrolled asthmatics and 16 healthy subjects. FeNO and peak expiratory flow (PEF) were measured by themselves twice daily at home for three weeks (asthmatics) or two weeks (healthy subjects), and daily mean and diurnal variations of FeNO and PEF levels were calculated. In uncontrolled asthmatics, treatment was intensified a week after study entry, and then control status was reevaluated after three to four weeks. Asthmatics were then divided into two groups; good or poor responders., Results: Diurnal variations of FeNO levels, as well as daily mean FeNO and PEF levels, in uncontrolled asthmatics before intensive treatment were significantly higher than those in healthy subjects, regardless of treatment response ( p  < 0.01). Furthermore, in the good responders, diurnal variations of FeNO levels were significantly decreased in the 1 st week ( p  < 0.05) of intensive treatment, whereas the daily mean FeNO levels significantly dropped in the 2 nd week ( p  < 0.05). In the poor responders, no such changes were observed in FeNO levels. In terms of PEF, only the daily mean levels were significantly elevated after the initiation of intensive treatment, regardless of treatment response., Conclusions: Diurnal variations of FeNO may contribute to predicting early therapeutic response to asthma treatment.

Objective: Retrograde leptomeningeal venous drainage (RLVD) of a dural arteriovenous fistula (dAVF) is associated with neurological morbidity and unfavorable outcomes. However, the direct damage to cortical neurons by dAVF with RLVD has not been elucidated. 123I-iomazenil (123I-IMZ) SPECT can reveal cerebral blood flow and cortical neuronal damage in early and late images, respectively. This study aimed to assess the cerebral venous congestive encephalopathy caused by dAVF using 123I-IMZ SPECT., Methods: Based on the pre- and posttreatment MRI findings, patients were divided into three groups: a normal group, an edema group, and an infarction group. Radioactive counts in the early and late images of 123I-IMZ SPECT were investigated using the affected-to-contralateral side asymmetry ratio (ACR)., Results: None of the patients in the normal group showed any symptoms related to venous congestion. In contrast, all the patients in the edema and infarction groups developed neurological symptoms. The ACR in early images in the edema group was significantly lower than that in the normal group and significantly higher than that in the infarction group. The ACR in the late images of the infarction group was significantly lower than those of the normal and edema groups. After treatment, the neurological signs disappeared in the edema group, but only partial improvement was observed in the infarction group. The ACR in early images significantly improved after treatment in the edema group, but the ACR in late images did not change in any groups., Conclusions: 123I-IMZ SPECT is useful for evaluating hemodynamic disturbances and neuronal damage in dAVFs. The reduction in early images was correlated with the severity of venous congestive encephalopathy, and the significant reduction in late images is a reliable indicator of irreversible venous infarction caused by RLVD.

Copper(I) oxide nanocubes were wrapped with an extremely uniform organic layer grown by self-controlled, Cu-mediated catalysis. This layer aided in retaining the initial cubic structure of the copper nanocubes during their use as a CO 2 reduction electrocatalyst, resulting in high CO 2 reduction selectivity by strong suppression of hydrogen evolution because of exclusion of water from the surface.

Objective: The first edition of guidelines for standardization of bone single photon emission computed tomography (SPECT) imaging was published in 2017, and the optimization and standardization are widely promoted. To the purpose, clarification of the factors related to image quality and quantitative values and their influence are required. The present study aimed to clarify and optimize the influence of patient body habitus on image quality and quantitative values in bone SPECT/CT., Methods: National Electrical Manufacturers Association body phantom (S-size) and custom-made large body phantoms (M-size and L-size) that simulate the abdomens of Japanese patients weighing 60, 80, and 100 kg, were used. Each phantom was filled with 99m Tc-solutions of 108  and 18 kBq/mL for the hot spheres and background, respectively. Dynamic SPECT acquisition was performed for 6000 s (150 s /rotation × 40 rotation). The data were divided into six projection data and reconstructed each acquisition time (150, 300, 450, 600, 750, 900 s, and single projection 6000 s). Image quality was evaluated for contrast (Q H, 17 mm ), background noise (N B, 17 mm ), contrast-to-noise ratio (CNR), maximum standardized uptake value (SUV max, 17 mm ), and visual assessment for a 17 mm hot sphere., Results: Image quality in the 300 s acquisition showed that values of Q H, 17 mm , CNR, and SUV max, 17 mm decreased (-16.7%, -11.8%, and -11.3%) for M-size and (-28.2%, -30.1%, and -21.7%) for L-size compared with S-size, respectively. No significant difference was observed in N B, 17 mm values. M-size and L-size required 1.2 and 2.3 times longer acquisition, to achieve same CNR as S-size. In visual assessment, 17 mm hot sphere could not be detected only in the L-size. When the Japanese bone SPECT guidelines criteria were applied in 600 s, the sphere could be detected between all phantoms., Conclusions: Patient body habitus significantly affects image quality and decreases the quantitative value in bone SPECT/CT. For the optimization, extend acquisition time according to the patient body habitus is effective for image quality. And for the standardization, it is important to achieve imaging conditions that meet the Japanese bone SPECT guidelines criteria to ensure adequate detectability., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background: Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. Methods: We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). Results: The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). Conclusion: This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge., Competing Interests: Competing Interests: Yoko Shibata and Hiroyuki Minemura received lecture fees and research grants from Chugai Pharmaceutical Co., Ltd. The other authors report no competing interests related to this study., (© The author(s).)

The non-coding GGGGCC hexanucleotide repeat expansion (HRE) in C9orf72 gene is a dominant cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This intronic mutation elicits the formation of nuclear and cytoplasmic inclusions containing RNA, RNA-binding proteins, and HRE-derived dipeptide repeat proteins (DPRs), leading to neurodegeneration via the gain-of-toxic function or loss-of-function of relevant proteins. Using C9-500 mice harboring ~500 repeats of the GGGGCC sequence in human C9orf72 gene, we investigated the effects of rifampicin against HRE-related pathological phenotypes. Rifampicin was administered intranasally to 4.5- to 5-month-old mice for 1 month, and their cognitive function and neuropathology were assessed by the Morris water maze test and immunohistochemical staining. Rifampicin treatment reduced the formation of RNA foci and cytoplasmic inclusions containing DPRs or phosphorylated TDP-43, and furthermore, the levels of phosphorylated double-strand RNA-dependent protein kinase (PKR) that regulates repeat-associated non-ATG (RAN) translation. Synapse loss in the hippocampus and neuronal loss and microglial activation in the prefrontal and motor cortices were also attenuated, and mouse memory was significantly improved. Our findings suggest a therapeutic potential of nasal rifampicin in the prevention of C9orf72 -linked neurodegenerative disorders.

Background: The epidemiology and risk of coronavirus disease 2019 (COVID-19) among travelers at international borders remain unclear., Methods: We conducted descriptive and individually matched case-control studies using a nationwide register for COVID-19 testing of travelers from 3 August to 31 October 2020 at airport/port quarantine stations across Japan. Case patients, defined as travelers positive for COVID-19 on arrival, were individually matched with 4 controls for arrival date and airport or port. We assessed associations between test positivity and traveler characteristics using conditional logistic regression analysis., Results: Overall, 157 507 travelers arriving from 146 countries/areas at 17 quarantine stations across Japan were tested for COVID-19. The percentage of test positivity during the study period was 0.35%. In the case-control study, with 536 case patients and 2144 controls, we found evidence of lower test positivity in travelers aged 3-19 years, female travelers, and travel corridor users (adjusted odds ratio [95% confidence interval], 0.36 [.22-.60], 0.71 [.56-.89], and 0.48 [.30-.77], respectively), whereas higher positivity was associated with arrival from South-East Asia (1.88 [1.33-2.65]) or lower-middle- or low-income countries (2.46 [1.69-3.58] and 7.25 [2.22-23.66], respectively), any symptom (4.08 [1.43-11.65]), and nasopharyngeal compared with saliva sampling (2.75 [1.85-4.09]). A higher 14-day average incidence in the countries of stay was also associated with higher test positivity (1.64 [1.16-2.33] and 3.13 [1.88-5.23] for those from countries and areas where the 14-day average incidence was from 10 to <100 and ≥100 cases per million, respectively)., Conclusions: These findings justify travel restrictions based on the epidemic situation in countries of stay, although underestimation of the epidemic in lower-income countries should be considered. A strict travel corridor could also reduce the risk of COVID-19 importation., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Type 2 diabetes mellitus is known to be a risk factor for Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. In AD, the cerebral accumulation of amyloid β (Aβ) triggers a pathological cascade leading to neurodegeneration. Plasma Aβ levels are thought to reflect the brain amyloid pathology and currently used as a diagnostic biomarker of AD. However, amyloid precursor protein and Aβ-generating enzymes, β- and γ-secretases, are widely expressed in various peripheral tissues. Previous reports have shown that glucose and insulin loading cause a transient increase of plasma Aβ in mice and humans. These findings led us to speculate that plasma Aβ is produced from glucose- and insulin-susceptible peripheral tissues to play a role in glucose and insulin metabolism. To test this hypothesis, we investigated the effects of glucose and insulin on Aβ secretion and the effect of Aβ on insulin secretion in vivo, ex vivo, and in vitro. Aβ was found to be secreted from β-cells of the pancreas along with insulin upon glucose stimulation. Upon insulin stimulation, Aβ was secreted from cells of insulin-targeted organs, such as adipose tissues, skeletal muscles, and the liver, along with their organokines. Furthermore, Aβ inhibited the glucose-triggered insulin secretion from β-cells, slowing down glucose clearance from the blood. These results suggest that peripheral Aβ acts as a negative modulator of insulin secretion. Our findings provide a possible mechanism linking diabetes to AD and call attention to how plasma Aβ levels are used in AD diagnosis.

The cell-to-cell transmission of tau aggregates is considered a mechanism underlying the intracerebral spreading of tau pathology in Alzheimer's disease (AD) and other tauopathies. Recent studies suggest that tau oligomers, rather than fibrils, participate in this process. We previously showed that intranasal rifampicin inhibits tau oligomer accumulation and improves cognition in tauopathy mice. In the present study, we examined the effects of nasal rifampicin on tau propagation in a new mouse model of tauopathy. A tau oligomer-rich fraction prepared from the brain of an AD patient was injected into a unilateral hippocampus of tau264 mice that express both 3-repeat and 4-repeat wild-type human tau. Rifampicin administration was started one week after the injection and performed three times a week for 24 weeks. Cognitive function and tau pathology were assessed by the Morris water maze test and brain section staining. Rifampicin treatment inhibited the spreading of tau oligomers from the injection site to other brain regions and neurofibrillary tangle formation in the entorhinal cortex. Synapse and neuronal loss in the hippocampus were also prevented, and cognitive function remained normal. These results suggest that intranasal rifampicin could be a promising remedy that halts the progression of tauopathy by inhibiting tau oligomer propagation.

To investigate whether the oral intake of slowly digestible α-glucan (SDG) could have a trophic (i.e., thickening) effect on their ileal mucosae, for 10 d, rats were given control (non-SDG), 10% isomaltodextrin (IMD) or 10% resistant maltodextrin (RMD) diets. In addition, experimental rat groups were further divided into two groups each and their diets either had or had not 1% sodium carboxymethylcellulose (CMC) added as a thickening agent. In the jejuna and the ilea, compared with control rats, the villus length and the mucosal thickness, but not the crypt depth, were significantly greater in the RMD-fed rats, with the trophic effect being weaker in the IMD-fed rats than in the RMD-fed rats. The colonic crypt depth was significantly greater in SDG groups than in the control group. The concentration of plasma glucagon-like peptide (GLP)-2 in the portal veins of the RMD group but not the IMD group was significantly higher than in the control group, with no effect of CMC supplementation on its concentration. The concentrations of cecal short-chain fatty acids did not significantly increase with SDG supplementation except for propionate concentration of the IMD-supplemented rats, compared with those in the control rats. We concluded that SDGs, especially RMD, thickened the mucosae of the rat distal small intestines. In particular, this effect of RMD but not IMD could have resulted from increased glucose available as a secretagogue of the trophic hormone GLP-2, in the ileum.

Background and Aims: Noninvasive, imaging diagnosis of gastrointestinal mesenchymal tumors (GIMTs) is still difficult. This study aimed to develop a novel diagnostic method of GIMTs via endoscopic ultrasonography (EUS) using circularity., Methods: In a derivation series, we retrospectively collected 50 GIMTs 2-5 cm in diameter of two institutions. After selecting one EUS still image showing the maximal area per lesion, two endoscopists who were blind to the histological diagnosis assessed circularity, a surrogate indicator of roundness (range, 0-1; 1 = a true circle), with an image-analyzing software. Median circularity of three types of GIMT was compared, and the cutoff value to differentiate a group from other groups was presented by drawing a receiver operating characteristic curve. Subsequently, we assessed the diagnostic ability of circularity in 91 GIMTs which were retrospectively collected from the other two institutions by using the optimal cutoff value presented in the derivation series., Results: The circularity in leiomyomas indicated 0.70 and was significantly lower than that of gastrointestinal stromal tumors (0.89), schwannomas (0.90), and their combined group. When leiomyomas were diagnosed as the circularity of <0.8305, which was presented as the optimal cutoff value, the diagnostic accuracy, sensitivity, and specificity in the validation series were 73.6%, 80.0%, and 72.4%, respectively., Conclusion: The data demonstrated that leiomyomas significantly exhibited more distortion than other GIMTs. That implies that the difference in shape, which is objectively determined as circularity, is useful to noninvasively discriminate leiomyomas from other GIMTs., (© 2022 S. Karger AG, Basel.)

Amyloidogenic protein oligomers are thought to play an important role in the pathogenesis of neurodegenerative dementia, including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies. Previously we demonstrated that oral or intranasal rifampicin improved the cognition of APP-, tau-, and α-synuclein-transgenic mice by reducing the amount of Aβ, tau, and α-synuclein oligomers in the brain. In the present study, to explore more effective and safer medications for dementia, we tested the drug combination of rifampicin and resveratrol, which is a multifunctional natural polyphenol with the potential to antagonize the adverse effects of rifampicin. The mixture was intranasally administered to APP-, tau-, and α-synuclein-transgenic mice, and their memory and oligomer-related pathologies were evaluated. Compared with rifampicin and resveratrol alone, the combinatorial medicine significantly improved mouse cognition, reduced amyloid oligomer accumulation, and recovered synaptophysin levels in the hippocampus. The plasma levels of liver enzymes, which reflect hepatic injury and normally increase by rifampicin treatment, remained normal by the combination treatment. Notably, resveratrol alone and the combinatorial medicine, but not rifampicin alone, enhanced the levels of brain-derived neurotrophic factor (BDNF) and its precursor, pro-BDNF, in the hippocampus. Furthermore, the combination showed a synergistic effect in ameliorating mouse cognition. These results show the advantages of this combinatorial medicine with regards to safety and effectiveness over single-drug rifampicin. Our findings may provide a feasible means for the prevention of neurodegenerative dementia that targets toxic oligomers., Competing Interests: TU, TK, and TT have applied for a patent on intranasal rifampicin and resveratrol combination for neurodegenerative dementia (PCT/JP2019/000278). TK and TT are the founders of Medilabo RFP, Inc., who is developing nasal rifampicin. This study received funding from Medilabo RFP, Inc., The funder had the following involvement with the study: TK proposed the drug combination study, and TT designed the study, conducted the drug administration, immunohistochemical staining, western blotting, and wrote the manuscript. The remaining 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 © 2021 Umeda, Sakai, Shigemori, Yokota, Kumagai and Tomiyama.)

Background: Three-dimensional (3D) visualization offers better depth recognition than two-dimensional (2D) imaging, thus helping to provide more useful information. We compared 3D and 2D endoscopy with regard to endoscopic recognition and endoscopic submucosal dissection (ESD) marking for superficial gastric neoplasia., Methods: ESD marking was performed on half of a neoplasia margin under 2D observation and the on other half under 3D observation for 28 gastric lesions (26 early gastric cancers and 2 adenomas). The accuracy of ESD marking was evaluated based on the distance between the pathological and endoscopic neoplasia margins measured on histology sections of ESD specimens. The technical ease of ESD marking and endoscopic lesion recognition (lesion morphology, lesion extent, and comprehensive endoscopic cognition) were assessed using visual analog scale (VAS) questionnaires., Results: The mean distance between the pathological and endoscopic margins under 3D observation (1.03 ± 0.80 mm) was significantly (p = 0.002) shorter than that under 2D observation (1.94 ± 1.96 mm). The VAS for technical ease of ESD marking under 3D observation was significantly better (p < 0.01) than that under 2D observation. The VAS for all aspects of endoscopic recognition under 3D observation was significantly better (p < 0.01) than under 2D observation., Conclusions: 3D flexible endoscopy achieved more accurate endoscopic recognition and ESD marking for superficial gastric neoplasia than a 2D approach in a clinical setting of ESD., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)