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Yojiro Umezaki,1 Motoko Watanabe,2 Yukiko Shinohara,2 Shiori Sugawara,2 Kaoru Kawasaki,2 Trang TH Tu,2 Takeshi Watanabe,2 Takayuki Suga,2 Anna Miura,2 Miho Takenoshita,2 Yusuke Sato,3 Ichiro Minami,4 Jun Oyama,5 Akira Toriihara,5 Tatsuya Yoshikawa,2 Toru Naito,1 Haruhiko Motomura,2 Akira Toyofuku2 1Section of Geriatric Dentistry, Department of General Dentistry, Fukuoka Dental College, Fukuoka 814-0193, Japan; 2Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 3Department of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 4Department of Removable Partial Prosthodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, Japan; 5Department of Diagnostic Radiology and Nuclear Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8548, JapanCorrespondence: Akira ToyofukuDepartment of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8548, JapanTel/Fax +81- 3-5803-5909Email toyoompm@tmd.ac.jpBackground: Phantom bite syndrome (PBS) is characterized by an uncomfortable sensation during occlusion without any evident abnormality. A recent case–control study with single-photon emission computed tomography (SPECT) using 99mTc-ethyl cysteinate dimer could not find the specific features of regional cerebral blood flow (rCBF), which might be due to the heterogeneity of PBS. We analyzed the brain images of PBS corresponding to the clinical features by studying PBS subgroups.Methods: This study contributes to elucidating the pathophysiology of PBS by evaluating regional brain perfusion on SPECT and its clinical features. We performed SPECT using 99mTc-ethyl cysteinate dimer in 44 patients with PBS. The SPECT images were analyzed qualitatively and quantitatively.Results: Asymmetrical rCBF patterns were detected, corresponding to symptom laterality. Patients with PBS with right-side symptoms showed right-side-predominant rCBF asymmetry in the parietal region and left-side-predominant rCBF asymmetry in the thalamus, and vice versa. Moreover, the analysis of the association between rCBF and patient behaviors revealed that patients who blamed their dentists for their symptoms tended to have a symmetrical rCBF pattern.Conclusion: Patients with PBS showed blood flow imbalance in the thalamus and parietal region corresponding to symptom laterality. There are two types of symmetrical and asymmetrical rCBF patterns in the pathophysiology of PBS despite similar clinical manifestations.Keywords: phantom bite syndrome, cerebral blood flow, single-photon emission computed tomography

Background and Aims: The increasing prevalence of obesity has significantly contributed to the global burden of colorectal cancer and the precancerous colorectal adenoma (CRA). Gut microbiota vary at each stage of colorectal carcinogenesis and participate in energy homeostasis. Elucidating gut microbiotal characteristics in obesity-related CRA may help prevent and treat colorectal tumors; however, this remains unclarified. Therefore, this study investigated the gut microbiota profile of patients with obesity-related CRA. Methods: This hospital setting-based cross-sectional study included 113 participants (66 [without CRA control group] and 37 [with CRA group]; each group was divided into obese and nonobese groups) who underwent screening colonoscopy between June 2019 and January 2020. Gut microbiota were analyzed using 16S rRNA and polymerase chain reaction techniques and the data compared between the aforementioned groups. Results: No between-group difference was observed in the diversity index; however, α diversity was the lowest in the obese CRA group. The CRA group had significantly higher and lower numbers of 26 and 17 genera, respectively. Genus Slackia was significantly lower in the obese CRA group than in the nonobese CRA group. Multivariate analysis of the quartiles according to genus Slackia relative abundance rates revealed that the first quartile was an independent risk factor for CRA (odds ratio, 3.57; 95% confidence interval 1.19–10.7). The proportion of equol reductase-positive participants was lowest in the obese CRA group (P = .04). Multivariate odds ratio for CRA was 5.46 (95% confidence interval 1.35–22.0) for genus Slackia and equol reductase-negative participants. Conclusion: Decreased abundance of genus Slackia and absence of equol reductase potentially influence obesity-related CRA development.

Many studies have confirmed the memory enhancement effect of production, generation and elaboration which can be effective after only one encoding. It is also known that greater memory enhancement effects can be obtained by combining multiple memory strategies during encoding. This study aimed to investigate whether the combination of production and self-generated elaboration enhances memory performance compared with production or generation alone. A total of 23 undergraduate and graduate students participated in this study. In the functional magnetic resonance imaging analysis, we explored the neural representation of remembering information after production and self-generated elaboration strategy. We set four encoding strategy conditions: (1) Read Silent (read without production), (2) Read Aloud (only production), (3) Add Silent (self-generated elaboration without production), (4) Add Aloud (production and self-generated elaboration). The retrieval performance and brain activity while retrieving the learned sentences after a one-week delay were examined. The behavioral results showed that the highest memory performance was for sentences encoded in Add Aloud. The interaction between production and self-generated elaboration was statistically significant. These results suggest that the memory enhancement effect of combining production and self-generated elaboration is not a simple addition nor synergistic facilitation effect. The imaging results showed that the following areas were related to the retrieval of the target encoded in the add aloud condition: the area related to integration of internal and external information (precuneus), area related to information rich stimuli (lateral occipital lobe), area related to self-involvement and inference of others' feelings (MPFC), area related to seen imagery (retrosplenial region) and area related to adjustment of movement (cerebellum). These results suggest that with an encoding strategy that combines production and self-generated elaboration, integrated auditory input of vocalizations and generated images, visual images of the scene, self-relevance, inference of other's feeling, movement by moving mouth are stored with the target and enhanced memory performance of AA.

Abstract Obesity is a major risk factor for colorectal cancer (CRC). Sustained hyperglycemia destabilizes tumor suppressor ten-eleven translocation (TET) 2, which is a substrate of AMPK, thereby dysregulating 5-hydroxymethylcytosine (5-hmC). However, the role played by this novel pathway in the development of obesity-related CRC is unclear. In this study, we aimed to evaluate the expression levels of TET2 and 5-hmC in obesity-related CRC and the effects of TET2 expression on the proliferation of CRC cells. To this end, surgically resected CRC samples from seven obese patients (Ob-CRC) and seven non-obese patients (nOb-CRC) were analyzed, and expression levels of the TET family and 5-hmC were compared between the groups. A decrease was observed in TET2 mRNA levels and 5-hmC levels in Ob-CRC compared to that in nOb-CRC. Furthermore, we used CRC cell lines to investigate the relationship between insulin, proliferation, and TET expression and AMPK. In cell lines, glucose and insulin treatments suppressed the expression of TET2 and increased cell proliferation. Downregulation of TET2 using siRNA also induced cell proliferation. An AMPK activator inhibited insulin- or glucose-stimulated cell proliferation and restored TET2 expression. We propose the AMPK-TET2-5-hmC axis as a novel pathway and potential therapeutic target in obesity-related CRC development.

This paper conducts the first trial to apply a masked language AI model and the “Gini coefficient” to the field of English study. We propose an algorithm named CLOZER that generates open cloze questions that inquiry knowledge of English learners. Open cloze questions (OCQ) have been attracting attention for both measuring the ability and facilitating the learning of English learners. However, since OCQ is in free form, teachers have to ensure that only a ground truth answer and no additional words will be accepted in the blank. A remarkable benefit of CLOZER is to relieve teachers of the burden of producing OCQ. Moreover, CLOZER provides a self-study environment for English learners by automatically generating OCQ. We evaluated CLOZER through quantitative experiments on 1,600 answers and show its effectiveness statistically. Compared with human-generated questions, we also revealed that CLOZER can generate OCQs better than the average non-native English teacher. Additionally, we conducted a field study at a high school to clarify the benefits and hurdles when introducing CLOZER. Then, on the basis of our findings, we proposed several design improvements.

Calanus glacialis/marshallae is a dominant zooplankton species in the Pacific Arctic Ocean that is widely distributed in shelf areas, and it plays a vital role in connecting primary production to higher trophic levels. Its phenology is well adapted to hydrography, but there is little available information about regional and diel changes in population structure and grazing features. In this study, we investigated C. glacialis/marshallae during autumn 2019 in the Eastern and Northeastern Chukchi and Canadian basins to reveal geographic and diel variations in population structure, body size, grazing activity, and fatty acid composition. The abundance of C. glacialis/marshallae was found to be high on the slopes and low on the shelves. Body size (prosome length) was well described by the Bělehrádek equation combined with in-situ temperature throughout the sampling region. Cluster analyses based on hydrographic parameters were divided into four regions: southern shelf, northern shelf, slope, and basin. The southern shelf was dominated by copepodite stage five (C5) transported from the Bering Sea by Pacific waters. C4 and C5 were dominant on the northern shelf, suggesting that they grew slower than those on the southern shelf, and the populations also exhibited higher concentrations of fatty acids originating from dinoflagellates than those originating from the pan-Arctic Ocean, indicating low productivity in the region. The population on the slope had the highest abundance, C4 was dominant, and large amounts of diatom-derived eicosapentaenoic acid (EPA). These features are attributed to the upwelling of populations and nutrients that support diatom growth. In the basin, the early copepodite stages of composition were distinctly higher than those recorded in previous studies, because larger amounts of organisms flow into the region, resulting in more extended reproduction periods. In the basin, small and large forms of C5 were simultaneously found, and the small form exhibited a diel grazing activity pattern, but the large forms did not. These findings suggest their well adaptation in changing of the Pacific Arctic Ocean.

The HHP inactivation behaviors of Niigata sake yeast Saccharomyces cerevisiae strain S9arg and its aerobic respiratory-deficient mutant strains were investigated after cultivating them in a YPD media containing 2% to 15% glucose, as well as in moromi mash, in a laboratory-scale sake brewing process. The piezotolerance of strain S9arg, shown after cultivation in a YPD medium containing 2% glucose, decreased to become piezosensitive with increasing glucose concentrations in YPD media. In contrast, the piezosensitivity of a mutant strain UV1, shown after cultivation in the YPD medium containing 2% glucose, decreased to become piezotolerant with increasing glucose concentrations in the YPD medium. The intracellular ATP concentrations were analyzed for an S. cerevisiae strain with intact aerobic respiratory ability, as well as for strain UV1. The higher concentration of ATP after cultivation suggested a higher energy status and may be closely related to higher piezotolerance for the yeast strains. The decreased piezotolerance of strain S9arg observed after a laboratory-scale sake brewing test may be due to a lower energy status resulting from a high glucose concentration in moromi mash during the early period of brewing, as well as a lower aeration efficiency during the brewing process, compared with cultivation in a YPD medium containing 2% glucose.

Abstract Objectives To assess the usefulness of linked color imaging (LCI), a recently developed image‐enhanced endoscopy technique, in the endoscopic diagnosis of eosinophilic esophagitis (EoE). Methods Thirty white light images (WLIs) and 30 WLI+LCI images collected from patients with and without EoE were randomly and blindly reviewed by 10 endoscopists, including four experts (Exs) and six non‐Exs. Edema, ring, exudate furrows, and strictures were rated on the adjusted EoE endoscopic reference score; the diagnosis of EoE was assessed. Using the kappa value, inter‐ and intra‐observer agreements were analyzed among endoscopists. Results WLI+LCI images had a higher diagnostic accuracy for EoE than WLIs (0.85 vs. 0.70, respectively), especially in non‐Exs or endoscopists with no experience with EoE patients. Inter‐observer agreement for WLI+LCI images statistically surpassed WLIs for furrows (kappa, 0.73 vs. 0.67, respectively; p = 0.0013), stricture (kappa, 0.51 vs. 0.39, respectively; p = 0.0072), and diagnosis (kappa, 0.67 vs. 0.57, respectively; p < 0.0001) of EoE. The increase in inter‐observer agreement in WLI+LCI images allowed for a reduction in the differences between the Exs and non‐Ex endoscopists. Intra‐observer agreement for WLI+LCI images surpassed WLIs for a ring (kappa, 0.62 vs. 0.43, p = 0.0052), and a similar trend was found in exudates, furrows, and diagnosis irrespective of the Exs or non‐Exs. Conclusions LCI can contribute to the improvement of the endoscopic diagnosis for EoE, with “moderate” to “substantial” consistency, by enhancing the visibility of abnormal findings, leading to reduced diagnostic disparities among endoscopists.

Abstract Alcohol consumption and smoking pose a significant risk for esophageal squamous cell neoplasia (ESCN) development in males; however, ESCN is often diagnosed in non-drinking and non-smoking females. The mechanisms underlying these differences remain elusive, and understanding them can potentially identify novel pathways involved in ESCN development. We performed short-read sequencing to identify somatic variants on a cancer panel targeting 409 genes using DNA extracted from the superficial squamous cell carcinoma (ESCC) tissues and adjacent non-neoplastic epithelium (NE), and immunohistochemical staining of the protein encoded by the target gene. All male patients (n = 117) were drinkers or smokers, whereas 45% of the female patients (n = 33) were not. Somatic variants were compared among three age-matched groups: 13 female ESCC patients with smoking and drinking habits (known-risk group, F-KR), 13 female ESCC patients without these habits (unknown-risk group, F-UR), and 27 males with ESCC and smoking and drinking habits (M-KR). In the NE, the frequencies of CDKN2A variants were significantly higher in F-UR than in F-KR and M-KR. In both ESCC and NE, p14ARF was significantly overexpressed in F-UR than in the other groups. In conclusion, CDKN2A might be important in ESCC development, independent of known risk factors.

Abstract Background and Aim Obesity affects the gut microbiome, which in turn increases the risk for colorectal cancer. Several studies have shown the mechanisms by which some bacteria may influence the development of colorectal cancer; however, gut microbiome characteristics in obese patients with colorectal cancer remain unclear. Therefore, this study evaluated their gut microbiome profile and its relationship with metabolic markers. Methods The study assessed fecal samples from 36 consecutive patients with colorectal cancer and 38 controls without colorectal cancer. To identify microbiotic variations between patients with colorectal cancer and controls, as well as between nonobese and obese individuals, 16S rRNA gene amplicon sequencing was performed. Results Principal coordinate analysis showed significant differences in the overall structure of the microbiome among the study groups. The α‐diversity, assessed by the Chao1 index or Shannon index, was higher in patients with colorectal cancer versus controls. The relative abundance of the genera Enterococcus, Capnocytophaga, and Polaribacter was significantly altered in obese patients with colorectal cancer, whose serum low‐density lipoprotein concentrations were positively correlated with the abundance of the genus Enterococcus; among the most abundant species was Enterococcus faecalis, observed at lower levels in obese versus nonobese patients. Conclusions This study demonstrated several compositional alterations of the gut microbiome in patients with colorectal cancer and showed that a reduced presence of E. faecalis may be associated with obesity‐related colorectal cancer development. The gut microbiome may provide novel insights into the potential mechanisms in obesity‐related colorectal carcinogenesis.

The purpose of this study was to establish a system for measuring breast underling pressure, evaluate the degree of sustained underling pressure, and verify basic data on the breast lifting distance to improve it. We measured the lifting distance and force at which 24 adult women felt comfortable when their breasts were lifted with an uncovered cloth. The results revealed that the larger the breast size, the greater the pull-up distance and the wider the lifting distance perceived as comfortable. The validity of the measurement method in this study was determined to be useful for the measurement of breast ptosis pressure and breast ptosis position because the measurement was performed at least three times per participant, and the error was small. In the future, we would like to clarify the type of brassiere that supports the breast and gives women a sense of comfort.