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Gastroenteritis is one of the most common infectious diseases, characterized by rapid onset of diarrhea with or without nausea, vomiting, fever, and abdominal pain (1,2). Enteric viruses and bacteria are [...]

The lung is a major dose-limiting organ for radiation therapy (RT) for cancer in the thoracic region, and the clarification of radiation-induced lung damage (RILD) is important. However, there have been few reports containing a detailed comparison of radiographic images with the pathological findings of radiation pneumonitis (RP)/radiation fibrosis (RF). We recently reported the upregulated expression of tenascin-C (TNC), an inflammation-associated extracellular matrix molecule, in surgically resected lung tissue, and elevated serum levels were elevated in a RILD patient. Therefore, we have developed a novel mouse model of partial lung irradiation and studied it with special attention paid to the computed tomography (CT) images and immunohistological findings. The right lungs of mice (BALB/c) were irradiated locally at 30 Gy/1fr, and the following two groups were created. In Group 1, sequential CT was performed to confirm the time-dependent changes in RILD. In Group 2, the CT images and histopathological findings of the lung were compared. RP findings were detected histologically at 16 weeks after irradiation; they were also observed on the CT images from 20 weeks. The immunostaining of TNC was observed before the appearance of RP on the CT images. The findings suggest that TNC could be an inflammatory marker preceding lung fibrosis.

We assessed the effect of rotavirus vaccination coverage on the number of inpatients with gastroenteritis of all ages in Japan. We identified patients admitted with all-cause gastroenteritis during 2011–2019 using data from the Diagnosis Procedure Combination system in Japan. We used generalized estimating equations with a Poisson distribution, using hospital codes as a cluster variable to estimate the impact of rotavirus vaccination coverage by prefecture on monthly numbers of inpatients with all-cause gastroenteritis. We analyzed 294,108 hospitalizations across 569 hospitals. Higher rotavirus vaccination coverage was associated with reduced gastroenteritis hospitalizations compared with the reference category of vaccination coverage 80%, adjusted incidence rate ratio was 0.87 [95% CI 0.83–0.90]). Our results show that achieving higher rotavirus vaccination coverage among infants could benefit the entire population by reducing overall hospitalizations for gastroenteritis for all age groups.

Testosterone production is important in males, and various physical and psychological abnormalities occur in individuals with low testosterone levels. In the present study, we aimed to examine the effects of longitudinal changes in total testosterone levels in the same cohort. We included 178 male subjects who visited our hospital multiple times between 2018 and 2023 for medical checkups for at least 3 years. The median baseline age and total testosterone level (TT) of the cohort were 61 years and 4.74 ng/mL, respectively. The patients were divided into four groups based on the difference in TT (ΔTT) between baseline and last visit (Q1, n = 45; Q2, n = 45; Q3, n = 44; Q4, n = 44). ΔTT values ranged from –3.07 to –0.78 ng/mL in Q1, from –0.75 to –0.05 ng/mL in Q2, from –0.03 to 0.73 ng/mL in Q3, and from 0.75 ng/mL to 3.4 ng/mL in Q4. The median ΔTT were –1.22 for Q1, –0.35 for Q2, +0.19 for Q3, and +1.43 for Q4. Decreased TT tended to increase body weight, body mass index, waist circumference, and visceral fat (p for trend 0.0136, 0.0272, 0.0354, and 0.0032, respectively), and decrease adiponectin level (p for trend 0.0219). Herein, we found that decreased TT increases visceral fat and decreases adiponectin levels.

Background: Tissue factor pathway inhibitors (TFPI1 and TFPI2) are ubiquitously distributed in humans and exhibit inhibitory activity against serine proteinases. TFPI1 inhibits the tissue factor (TF)-dependent extrinsic coagulation pathway, while TFPI2 modulates extracellular matrix remodeling. TFPI2 has been reported to be an epigenetically silenced tumor suppressor and independent prognostic factor in various human cancers. However, elevated serum levels of TFPI2 have been observed in ovarian and endometrial cancers compared to healthy controls, with increased levels correlating with poor prognosis in endometrial cancer. This raises the question of why the tumor suppressor TFPI2 is elevated in the blood of patients with gynecological cancers and is associated with adverse outcomes. Methods: A comprehensive literature search was performed in PubMed and Google Scholar without time restriction. Results: TFPI2 gene expression may be influenced by both cancer cell-specific gene expression profiles (e.g., oncogenic signaling pathways) and epigenetic modifications (e.g., DNA methylation, histone modifications, and non-coding RNAs). Although TFPI2 generally exhibits an anti-invasion effect in most human cancers, it has been reported to have a paradoxical pro-invasive effect in certain cancers. TFPI2 facilitates cancer invasion through aberrant alternative splicing or through a pathophysiological process known as angiotropism or vasculogenic mimicry. The overproduction of TFPI2 in the tumor microenvironment may reinforce the extracellular matrix, thereby enhancing tumor cell adhesion and invasion. Conclusion: This review summarizes the current understanding of the seemingly contradictory functions of TFPI2 in human malignancies, primarily focusing on the mechanisms regulating its expression and function, and discusses future prospects for translational research.

Abstract Individuals with autism spectrum disorder (ASD) have a higher prevalence of social memory impairment. A series of our previous studies revealed that hippocampal ventral CA1 (vCA1) neurons possess social memory engram and that the neurophysiological representation of social memory in the vCA1 neurons is disrupted in ASD-associated Shank3 knockout mice. However, whether the dysfunction of Shank3 in vCA1 causes the social memory impairment observed in ASD remains unclear. In this study, we found that vCA1-specific Shank3 conditional knockout (cKO) by the adeno-associated virus (AAV)- or specialized extracellular vesicle (EV)- mediated in vivo gene editing was sufficient to recapitulate the social memory impairment in male mice. Furthermore, the utilization of EV-mediated Shank3-cKO allowed us to quantitatively examine the role of Shank3 in social memory. Our results suggested that there is a certain threshold for the proportion of Shank3-cKO neurons required for social memory disruption. Thus, our study provides insight into the population coding of social memory in vCA1, as well as the pathological mechanisms underlying social memory impairment in ASD.

Abstract Background Recently, real‐world data have been recognized to have a significant role for research and quality improvement worldwide. The decision on the existence or nonexistence of postoperative complications is complex in clinical practice. This multicenter validation study aimed to evaluate the accuracy of identification of patients who underwent gastrointestinal (GI) cancer surgery and extraction of postoperative complications from Japanese administrative claims data. Methods We compared data extracted from both the Diagnosis Procedure Combination (DPC) and chart review of patients who underwent GI cancer surgery from April 2016 to March 2019. Using data of 658 patients at Kyoto University Hospital, we developed algorithms for the extraction of patients and postoperative complications requiring interventions, which included an invasive procedure, reoperation, mechanical ventilation, hemodialysis, intensive care unit management, and in‐hospital mortality. The accuracy of the algorithms was externally validated using the data of 1708 patients at two other hospitals. Results In the overall validation set, 1694 of 1708 eligible patients were correctly extracted by DPC (sensitivity 0.992 and positive predictive value 0.992). All postoperative complications requiring interventions had a sensitivity of >0.798 and a specificity of almost 1.000. The overall sensitivity and specificity of Clavien–Dindo ≥grade IIIb complications was 1.000 and 0.995, respectively. Conclusion Patients undergoing GI cancer surgery and postoperative complications requiring interventions can be accurately identified using the real‐world data. This multicenter external validation study may contribute to future research on hospital quality improvement or to a large‐scale comparison study among nationwide hospitals using real‐world data.

Background: Ovarian cancer is often characterized by aggressive growth and chemoresistance, leading to a poor prognosis. The energy and nutrient acquisition through metabolic reprogramming has been reported to facilitate cancer cell proliferation, invasion, and metastasis. Therefore, a therapeutic strategy to consider is to rewire energy metabolism. Mitochondrial dynamics have a profound impact on the metabolic profiles. In this review, we summarize the current understanding of the molecular mechanisms governing mitochondrial dynamics and their impact on cell proliferation and invasion and discuss future perspectives for therapeutic strategies and research directions. Methods: A search was conducted for literature published up to 30 June 2023 using the online databases PubMed and Google Scholar in this narrative literature review. Results: Mitochondria are essential for regulating metabolic reprogramming to meet the increasing energy demand for rapid cancer cell proliferation and invasion. A metabolic switch from OXPHOS to glycolysis may promote invasion, and OXPHOS-driven metabolism may be associated with proliferation, chemoresistance, and stemness. Many ovarian cancer cells are known to favor glycolysis over OXPHOS, but the opposite takes place in the subpopulation of cancer cells. The preference for glycolysis versus OXPHOS in ovarian cancer cells may be determined by histopathologic types, the unique genetic profile of energy metabolism, and intrinsic (e.g., oncogenic signaling) and extrinsic (e.g., nutritional status and hypoxia) factors. Conclusions: Preclinical studies suggest that mitochondrial dynamics regulators have therapeutic potential in ovarian cancer, but some factors limit their beneficial effects.

Abstract Background Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung injury with high mortality; no approved medication exists. Efficacy and safety of bone marrow–derived, allogeneic, multipotent adult progenitor cells (invimestrocel) plus standard treatment in patients with ARDS caused by pneumonia was evaluated. Methods A randomized, open-label, standard therapy–controlled, phase 2 study (January 2019–September 2021) conducted in 29 centers in Japan. Patients with ARDS caused by pneumonia, with extensive early fibroproliferation on high-resolution computed tomography and low risk of systemic organ failure identified by an Acute Physiology and Chronic Health Evaluation (APACHE II) score were included. Patients were randomized 2:1 to receive a single intravenous infusion of 9.0 × 108 cells of invimestrocel (administered at a rate of up to 10 mL/min over 30–60 min by free flow) plus standard treatment (N = 20) or standard treatment (N = 10) consistent with the clinical practice guidelines of the Japanese Respiratory Society for the management of ARDS. Primary endpoint was ventilator-free days (VFDs) through day 28 after study treatment. Analysis of covariance was performed with treatment group, age, partial pressure arterial oxygen/fraction of inspired oxygen ratio, and APACHE II score as covariates. Results Median (interquartile range) number of VFDs was numerically higher in the invimestrocel group versus standard group (20.0 [0.0–24.0] vs 11.0 [0.0–14.0]) but was not statistically significantly different (least square [LS] means [95% confidence interval (CI)]: invimestrocel group, 11.6 [6.9–16.3]; standard group, 6.2 [− 0.4 to 12.8]; LS mean difference [95% CI], 5.4 [− 1.9 to 12.8]; p = 0.1397). Ventilator weaning rate at day 28 was 65% (13/20) versus 30% (3/10), and mortality rate was 21% (4/19) versus 29% (2/7) at day 28 and 26% (5/19 patients) versus 43% (3/7 patients) at day 180, for the invimestrocel and standard groups, respectively. No allergic or serious adverse reactions were associated with invimestrocel. Conclusions In Japanese patients with ARDS caused by pneumonia, invimestrocel plus standard treatment resulted in no significant difference in the number of VFDs but may result in improved survival compared with standard treatment. Invimestrocel was well tolerated. Trial registration: ClinicalTrials.gov, Identifier: NCT03807804; January 8, 2019; https://clinicaltrials.gov/ct2/show/NCT03807804 .

BackgroundClinicians' research activities reportedly improve their healthcare performance. Presenting research at conferences may be related to improved patient care outcomes; however, few studies have investigated this relationship. Thus, we examined the association between presenting at conferences and the mortality of patients hospitalized for acute myocardial infarction.MethodsWe analyzed an administrative database of acute care hospitals in Japan. The study compared patients admitted to hospitals in which physicians made at least one conference presentation during the patient's admission year (Presentation Group) with those admitted to hospitals with no conference presentations (Control group). We performed multivariable logistic regression analyses to estimate the risk of all-cause in-hospital mortality. Five models were fitted: a Crude model, unadjusted; Model 1, adjusted for personal factors, including sex, age, Killip classification, and so on; Model 2, adjusted for Model 1 plus hospital factors; Model 3 was a multilevel analysis clustered by hospital codes and adjusted for the same variables as Model 1; Model 4 was adjusted for Model 1 plus evidence-based practices through causal mediation analysis.ResultsAfter excluding 3,544 patients with missing Killip classification or ambulance use, data for 56,923 patients in 384 acute care hospitals were analyzed. Drug prescription in accordance with the evidence was significantly greater in the Presentation group than in the Control group. Moreover, conference presentation was significantly associated with lower in-hospital mortality in all models (Odds ratios (OR) = 0.68, 95% Confidence intervals (CIs): 0.65 to 0.72 in the Crude model; OR = 0.73, 95% CIs: 0.68 to 0.79 in Model 1; OR = 0.76, 95% CIs: 0.70 to 0.82 in Model 2; OR = 0.84, 95% CIs: 0.76 to 0.92 in Model 3; OR = 1.00, 95% CIs: 0.92 to 1.09 in Model 4).ConclusionThe promotion of scholarly activities such as conference presentations might improve patient outcomes through increased evidence-based practice.

BackgroundBiosimilars have the potential to save a significant amount of money in cancer treatment costs. However, barriers exist in the adoption of biosimilar products. Japan introduced a new health policy in 2022 to promote the use of biosimilars in oncology by offering financial incentives to eligible hospitals. This study aims to examine the association between these financial incentives and prescription patterns.MethodsThe study analyzed Diagnosis Procedure Combination (DPC) data to assess the impact of the new health policy on the use of biosimilar products in oncology. The policy provided an additional fee for hospitals using biosimilar products. The study included patients with specific types of cancer and analyzed the proportion of monthly biosimilar prescriptions using the number of prescriptions of reference and biosimilar products. A generalized synthetic control method was used for analysis.ResultsFrom April 2020 to March 2023, the study involved 27,737 patients in 114 hospitals, with 63 eligible hospitals receiving financial incentives. The average number of prescriptions of the drugs (rituximab, trastuzumab, and bevacizumab) increased gradually in both eligible and ineligible hospitals. The financial incentives were associated with a significant increase in the proportion of biosimilar product prescriptions, with a monthly increase of 0.092 per month (95% CI, 0.040-0.145) [9.2%, 95% CI, 4.0-14.5] compared to ineligible hospitals.ConclusionOur study indicates that providing financial incentives to hospitals to utilize biosimilar products increased their prescriptions. Japan's recent health policy of moderate financial incentives is an effective approach to increasing prescriptions of biosimilar products.