Fosfomycin is a highest priority critically important antimicrobial in medical settings and is approved for use in cattle, fish, and humans in Japan. Breakpoints for fosfomycin differ between the antimicrobial susceptibility test guidelines of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Although important for public health, information on the prevalence of fosfomycin-resistant bacteria and mobile fosfomycin resistance genes (fos) in bacteria of nonhuman origin remains insufficient. In this study, we investigated Escherichia coli strains isolated from animals (cattle, pigs, chickens, and dogs) and the association of these with environments in Japan to determine the prevalence of fosfomycin-resistant E. coli based on CLSI and EUCAST, as well as fos gene prevalence. Susceptibility testing for fosfomycin was retrospectively conducted in 2,057 E. coli, and fos genes were detected in fosfomycin-resistant E. coli. Whole-genome sequencing of fos-positive E. coli was performed. The resistance rates to fosfomycin according to CLSI and EUCAST guidelines were 0.6% and 11.7%, respectively. The fosA3 gene was detected in three E. coli isolates (from one cow and two dogs) in Japan. Two fosA3-positive strains harbored the blaCTX-M-14 or blaCTX-M-65 gene located on the same plasmids. The genetic structures of fosA3-carrying plasmids were almost identical to those reported in Japan and China. Herein, we report the prevalence of fosfomycin resistance in Japan, including fosfomycin-nonapproved fields, showing that these may serve as reservoirs of fosfomycin-resistant bacteria and fos genes carried on globally disseminated mobile genetic elements.

Text Responses to dietary fiber supplementation vary markedly among individuals, yet no validated platform exists to prospectively identify optimal fiber types based on individual gut microbiome function. Here we present My Dietary Fiber Finder (MyDFF), an ex vivo functional screening platform that predicts optimal dietary fibers for individual gut microbiomes through direct fermentation profiling. For each participant, the dietary fiber with the highest saccharification index (SI) was designated M-PDF, and that with the lowest SI was designated L-PDF. In a crossover trial involving eight healthy Japanese adults (72 longitudinal observations, each participant serving as their own control), the pre-specified per-participant analysis (Dunnett's test) showed that M-PDF significantly increased fecal volatile fatty acid (VFA; acetate + propionate + butyrate) concentrations over baseline in two of eight participants and total short-chain fatty acid (SCFA) concentrations in one, whereas the non-personalized fiber (L-PDF) did so in none. Post hoc group-level analysis confirmed a significant increase over baseline for M-PDF (total VFA and total SCFA, both p < 0.01) but not for L-PDF, and in a within-participant comparison M-PDF exceeded L-PDF in seven of eight participants (mean difference = 32.4 μmol/g; 95% CI: 8.7-56.1; p = 0.014; Cohen's d = 1.14). However, the magnitude of the pre-intervention saccharification-index differential between the two fibers did not significantly correlate with the magnitude of the in vivo VFA response differential across participants (Pearson r = 0.082, p = 0.85), indicating that the assay did not quantitatively predict response magnitude. Exploratory 16S rRNA gene sequencing analysis showed no significant cohort-level shift in overall gut microbial community composition during either intervention phase. In four separate validation donors, individual fermentation profiles remained relatively stable over the observed 3-9-month follow-up. These proof-of-concept findings support the potential of function-based framework for personalized prebiotic design and motivate larger validation studies.

BackgroundDepression has been associated with various chronic conditions, including metabolic syndrome (MetS), but findings from Japanese studies have been inconsistent and are limited to cross-sectional design. We therefore examined the longitudinal association between depressive symptoms and incidence of MetS and its components in middle-aged Japanese workers.MethodsData were analysed from 2969 public servants (aged 35-65, 73.1% male) in the Aichi Workers' Cohort Study who were free of MetS at baseline (2013), with at least one follow-up assessment (between 2014 and 2018). Depressive symptoms were assessed at baseline using the 11-item Centre for Epidemiological Studies Depression scale (CES-D-11) and categorized into tertiles: first tertile (0-4), second tertile (5-7), and third tertile (≥8). MetS was defined by the harmonized criteria for Japanese, based on waist circumference (≥90 cm for men and ≥80 cm for women), triglycerides, HDL cholesterol, blood pressure, and blood glucose levels. Multivariable logistic regression estimated ORs and 95% CIs. Restricted cubic splines and piecewise logistic regression evaluated non-linearity and a threshold.ResultsDuring five years, 391 participants (13.2%) developed MetS, with a cumulative incidence rate of 10.2% in the first tertile, 15.8% in the second tertile, and 14.9% in the third tertile. In the fully adjusted model, participants in the second and third tertile had higher odds of incident MetS (OR: 1.89, 95% CI, 1.44-2.48; OR: 1.92, 95% CI, 1.40-2.64, respectively) and high triglycerides (OR: 1.43, 95% CI, 1.08-1.90; OR: 1.80, 95% CI, 1.31-2.48, respectively) compared with those in the first tertile. Restricted cubic spline suggested non-linearity (p < 0.001) with a threshold at CES-D-11 approximately 10. Below this threshold, each 1-SD increase in CES-D-11 was associated with higher odds of incident MetS (OR 1.59, 95% CI, 1.31-1.92).ConclusionDepressive symptoms were associated with incident MetS among middle-aged Japanese workers, particularly with high triglyceride component. The association appeared non-linear, with risk increasing up to a CES-D-11 score of approximately 10 and then plateauing. This potential threshold may help improve understanding of the relationship between depressive symptoms and MetS risk, although further studies are needed before it can be used for risk stratification and prevention efforts.

As a second-line treatment for first-line steroid-refractory acute GVHD, ruxolitinib was proven to be significantly more effective than control therapies (nine commonly used therapy options) in a prospective, randomized trial. However, it could sometimes be difficult to administer ruxolitinib for patients with cytopenia or who have difficulty taking it orally regularly. The present retrospective study compared the outcomes of second-line mesenchymal stromal cell (MSC) and antithymocyte globulin (ATG) therapies following first-line steroid therapy for acute GVHD. Clinical data for the total 1120 patients who received MSC (n = 777) and ATG (n = 343) as second-line therapy following first-line steroid therapy for acute GVHD from 2016 to 2022, when both therapies were covered by health insurance in Japan, were extracted from Japanese stem cell transplantation registry data. Overall response rates (ORRs) on day 28 of the MSC and ATG therapies were 62.7% and 51.0%, respectively (multivariate analysis: odds ratio, 1.56; P = 0.001). ORRs for skin, liver, and gastrointestinal tract acute GVHD were 66.3% versus 57.5% (1.43, P = 0.063), 33.1% versus 25.7% (1.18, P = 0.636), and 66.3% versus 49.8% (1.96, P < 0.001), respectively. The incidences of invasive fungal infection and viral infection within the first 100 days after the start of second-line therapy were 3.9% versus 8.2% (Fisher's exact test: P = 0.005) and 13.4% versus 25.1% (P < 0.001), respectively. However, non-relapse mortality, the relapse rate, and overall survival did not differ between MSC and ATG therapies. Furthermore, the propensity score-matched analysis yielded results consistent with the findings described above. In conclusion, this retrospective study demonstrated that the ORR based on whole body assessment and the ORR based on gastrointestinal tract stage assessment were both significantly higher with MSC therapy than with ATG therapy. However, prospective, randomized, controlled trials are necessary for a more accurate comparison.

Artificial intelligence (AI) has advanced rapidly in healthcare, with large language models (LLMs) like ChatGPT-4o showing potential in education and clinical support. This study evaluated the performance of ChatGPT-4o on oral surgery-related questions from the Japanese National Dental Examination, focusing on how visual materials impact accuracy. Questions were categorized by type (general knowledge vs clinical practice), number of correct answers required, and presence of visual materials (e.g., radiographs, models). The comparison of correct and incorrect answers according to the number of visual materials was performed using the Mann-Whitney U-test, while logistic regression was used to assess the influence of specific visual content types. ChatGPT-4o performed well on general knowledge questions but showed lower accuracy on questions requiring clinical decision-making . The presence of multiple visual materials significantly reduced accuracy, with panoramic radiographs and dental models showing the strongest negative effects (odds ratios 0.46 and 0.45, respectively; both P = 0.002). Other visual materials, such as computed tomography/magnetic resonance imaging scans, had no significant impact. These findings highlight the strengths of ChatGPT-4o in processing structured textual data and its limitations in interpreting visual or procedural content. Enhancing AI-assisted dental education will require domain-specific training data and the development of multimodal models capable of integrating both text and images. This study informs future applications of AI in oral surgery education.

Background/Objectives: To develop and validate a simple prediction model for identifying individuals with low fat-free mass index (FFMI) using routinely available clinical variables. Methods: A total of 8736 individuals were included (mean age = 54.2 years). Among men, 1674 (40.1%) had a low FFMI (<18 kg/m[2]), while among women, 2160 (47.3%) had a low FFMI (<15 kg/m[2]). Candidate predictors were preprocessed to reduce redundancy and multicollinearity. Repeated LASSO logistic regression and XGBoost-based SHAP analysis were used to identify robust predictors, and sex-specific logistic regression models were developed using the final selected variables. Model performance was evaluated using 500 repeated 8:2 train-test splits, calibration analysis, risk stratification, and decision curve analysis (DCA). Results: BMI and estimated GFR (eGFR) were consistently selected as key predictors and were used to construct the final sex-specific models. The BMI-eGFR model showed excellent discrimination. Calibration plots demonstrated good agreement between predicted probabilities and observed event rates. Mean held-out sensitivities and specificities were 0.861/0.875 in men and 0.869/0.805 in women, respectively. DCA showed that the model provided a higher net benefit than treat-all or treat-none strategies over most of the evaluated threshold range of 0.05-0.50. Conclusions: Our model for predicting low FFMI may be helpful when direct muscle mass measurement is not readily available.

Microbial dysbiosis and disrupted mucosal immune homeostasis are integrally involved in the pathogenesis of inflammatory bowel diseases (IBDs). Live biotherapeutic products (LBPs) offer a potential therapeutic strategy to restore beneficial microbes and mitigate disease. We investigated the therapeutic efficacy of 2 LBPs, human Clostridia consortia 17-mix and 11-mix, by treating established colitis in murine models. Both LBPs exhibited therapeutic effects in T cell-mediated chronic colitis models induced by human microbiota and in pathobiont-driven gnotobiotic colitis models established with combinations of IBD-relevant human-derived strains. Metagenomic and metabolomic analyses elucidated mechanisms that go beyond established functions driven by short-chain fatty acids (SCFAs) and interleukin (IL)-10-producing regulatory T cells. Notably, LBPs exerted therapeutic effects by directly inhibiting resident pathobionts and through IL-10-independent activation of host anti-inflammatory aryl hydrocarbon receptor (AhR) pathways by bacterial tryptophan metabolites. These results elucidate SCFA- and IL-10-independent protective mechanisms exerted by defined resident bacterial strains that are depleted in IBD dysbiosis.