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Introduction: High-resolution manometry (HRM) allows assessment of esophagogastric junction (EGJ) disruption. While type 3 EGJ predicts definitive gastroesophageal reflux disease (GERD), type 2 EGJ is less clearly implicated in GERD pathogenesis. This study aimed to characterize physiologic findings in type 2 EGJ to determine if the HRM-based Milan Score can define GERD within type 2 EGJ., Methods: 535 patients with suspected GERD who underwent HRM and reflux monitoring were retrospectively analyzed. Clinical, HRM, and reflux study data were compared between the EGJ morphology subtypes, with objective GERD defined according to Lyon Consensus 2.0. The Milan Score, a novel metric that integrates ineffective esophageal motility, EGJ-contractile integral, EGJ morphology, and straight leg raise response, was abnormal when ≥ 137 (risk rate 50% for GERD). Receiver operating characteristic (ROC) curve analysis was performed to assess the accuracy of the Milan Score to predict objective GERD., Results: Type 3 EGJ was associated with the highest rate of objective GERD, followed by type 2 and type 1 EGJ (p < 0.001), with a corresponding stepwise increase in AET from type 1 to 3 EGJ (p < 0.001). Type 2 EGJ with Milan Score < 137 resembled type 1 EGJ (objective GERD in 23.6% vs. 33.2%, p = 0.09), and type 2 EGJ with score ≥ 137 resembled type 3 EGJ (objective GERD in 88.2% vs. 78.8%, p = 0.11). On ROC analysis, the Milan Score had an area under the curve of 0.858., Conclusion: While type 2 EGJ includes varying GERD severity, the Milan Score can segregate patients at risk for objective GERD., (© 2025 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objective: The tumor microenvironment characterized by heterogeneously organized vasculatures causes intra-tumoral heterogeneity of oxygen partial pressure at the cellular level, which cannot be measured by current imaging techniques. The intra-tumoral cellular heterogeneity may lead to a reduction of therapeutic effects of radiation. The purpose of this study was to investigate the effects of the heterogeneity on biological effectiveness of H-, He-, C-, O-, and Ne-ion beams for different oxygenation levels, prescribed dose levels, and cell types.&#xD;Approach. The intra-tumoral cellular distributions were simulated with a numerical tumor model for average oxygen pressures ranging from 2.5 to 15 mmHg. The relative biological effectiveness (RBE)-weighted dose distributions of 3-15 Gy prescribed doses were planned for a cuboid target with the five ion species for constant values. Radiosensitivities of human salivary gland tumor (HSG) and Chinese hamster ovary (CHO) cells were investigated. The planned dose distributions were then recalculated by taking the heterogeneity into account. &#xD;Main results. As decreased and prescribed dose increased, the biological effectiveness of the ion beams decreased due to the heterogeneity. The reduction in biological effectiveness was pronounced for lighter H- and He-ion beams compared to heavier C-, O-, and Ne-ion beams. The RBE-weighted dose in the target for HSG (CHO) cells decreased by 41.2% (44.3%) for the H-ion beam, while it decreased by 16.7% (14.7%) for the Ne-ion beam at a prescribed dose of 15 Gy under a of 2.5 mmHg.&#xD;Significance. The intra-tumoral cellular heterogeneity causes a significant reduction in biological effectiveness of ion beams. These effects should be considered in estimation of therapeutic outcomes., (© 2025 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Pleural tuberculoma is often observed during treatment for tuberculous pleurisy; however, this condition is rarely found as a solitary pleural nodule in patients without a history of tuberculosis treatment, and no cases have been reported in children. We report a case of a 12-year-old boy with pleural tuberculoma presenting as a solitary mass. He had a fever and cough that prompted chest radiography, which revealed a mass in the right lung. Symptoms improved with antibacterial medication; however, computed tomography (CT) revealed a 4.5-cm pleural mass that partially bordered the ribs. CT-guided biopsy revealed a necrotizing granuloma, but the real-time polymerase chain reaction result for Mycobacterium tuberculosis was negative. Malignant diseases, such as osteosarcoma, could not be ruled out; thus, surgical resection was performed, and pleural tuberculoma was diagnosed. The patient was treated with antituberculosis drugs for 6 months, and no recurrence was observed in the following 2 years. Pleural tuberculomas should be considered in the differential diagnosis of solitary pleural tumors, especially in countries where tuberculosis is endemic., (Copyright © 2025 by the American Academy of Pediatrics.)

Background/aim: MicroRNAs (miRNAs) have been highlighted as non-invasive clinical biomarkers in liquid biopsy. This study aimed to investigate the clinical significance of circulating tumor suppressors, precursor-miR-488 (pre-miR-488) and miR-488-5p, in the blood of patients with gastric cancer (GC)., Materials and Methods: The expression levels of pre-miR-488 and miR-488-5p in tumor tissues and blood were measured using RT-qPCR, and the clinicopathological and prognostic significance of their expression was assessed in patients with GC. Next, pathway analysis of miR-488-5p expression in GC tissues was performed by gene set enrichment analysis (GSEA) using the TCGA dataset. Finally, pre-miR-488 in exosomes from the plasma of GC patients was analyzed using RT-qPCR., Results: Both pre-miR-488 and miR-488-5p were down-regulated in tumor tissues, whereas their expression in the blood was significantly higher in patients with GC than in healthy controls. Low expression of pre-miR-488 or miR-488-5p in the blood was associated with poor prognosis in patients with GC. Furthermore, low pre-miR-488 expression in the blood was an independent poor prognostic factor for overall survival. miR-488-5p expression tended to be negatively correlated with the expression of gene sets involved in epithelial-mesenchymal transition and hypoxia. pre-miR-488 was detected in exosomes isolated from the plasma of patients with GC., Conclusion: Circulating pre-miR-488 and miR-488-5p expression in the blood may serve as novel prognostic biomarkers for patients with GC, predicting clinical outcomes and guiding therapeutic strategies., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Stress is a significant cause of mental disorders, for which effective treatments remain limited due to an insufficient understanding of its pathogenic mechanisms. Recent research has increasingly focused on non-neuronal cells to elucidate the molecular mechanisms underlying psychopathology. In this review, we summarize the current knowledge on how non-neuronal cells in the central nervous system, including microglia, astrocytes, and oligodendrocytes, respond to peripherally derived stress-related factors and how these responses contribute to the development of mental disorders. A more comprehensive understanding of stress-induced alterations, with careful consideration of the type and timing of stress exposure, will provide fundamental insights into the pathogenesis of diverse stress-related mental disorders., (© 2024 International Society for Neurochemistry.)

Purpose: Double-tract reconstruction (DTR) is one of the major procedures following proximal gastrectomy (PG) with anti-reflex function for the esophagus. Although many studies demonstrated the feasibility of laparoscopic DTR, there is a lack of research on robotic DTR. We aimed to assess the safety and feasibility of robotic DTR following PG., Methods: Esophagojejunostomy was performed with a robotic stapler under endoscopic observation using the TilePro function of the Davinci Xi surgical system. The gastrojejunostomy procedure slightly differed depending on the size of the remnant stomach. Along with short-term surgical outcomes, long-term outcomes were compared based on the size of the remnant stomach., Result: Thirty patients underwent robotic DTR. The median value of operative bleeding was 10 mL, although the median operative and reconstruction times were 398 and 119 min, respectively. Anastomotic complications were absent, and reflux esophagitis was not observed endoscopically 1 year after operation. Body weight loss, symptoms, and blood test findings did not differ significantly., Conclusion: Robotic DTR may be a safe and favorable procedure in terms of the postoperative course and incidence of reflux esophagitis., (© 2024 The Author(s). Asian Journal of Endoscopic Surgery published by Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background and Aims: To prevent end-stage renal disease caused by diabetic kidney disease, we created a predictive model for high-risk patients using machine learning., Methods and Results: The reference point was the time at which each patient's estimated glomerular filtration rate (eGFR) first fell below 60 mL/min/1.73 m 2 . The input period spanned the reference point to 1 year prior. The primary endpoint was a 50% decrease in eGFR from the mean of the input period over the 3 year evaluation period. We created predictive models for patients' primary endpoints using time series data of various variables over the input period. Among 2,533 total patients, 1,409 had reference points, 31 had records for their input and evaluation periods and had reached their primary endpoints, and 317 patients had not. The area under the curve (AUC) of the predictive model peaked (0.81) when the minimum eGFR, the difference between maximum and minimum eGFR, and both maximum and minimum urinary protein values were included in the features., Conclusion: The accuracy of prognosis prediction can be improved by considering the variable components of urinary protein and eGFR levels. This model will allow us to identify patients whose renal functions are relatively preserved with eGFR of more than 60 mL/min/1.73 m 2 and are likely to benefit clinically from immediate treatment intensification., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Liquid biopsy using circulating tumor DNA (ctDNA) has been reported to be less invasive and effective for comprehensive genetic analysis of heterogeneous solid tumors, including decision-making for therapeutic strategies, predicting recurrence, and detecting genetic factors related to treatment resistance in various types of cancers. Breast cancer, colorectal cancer, and lung cancer are among the most prevalent malignancies worldwide, and clinical studies of liquid biopsy for these cancers are ongoing. Liquid biopsy has been used as a companion diagnostic tool in clinical settings, and research findings have accumulated, especially in cases of colorectal cancer after curative resection and non-small cell lung cancer (NSCLC) after curative chemoradiotherapy, in which ctDNA detection helps predict eligibility for adjuvant chemotherapy. Liquid biopsy using ctDNA shows promise across a wide range of cancer types, including breast cancer, and its clinical applications are expected to expand further through ongoing research. In this article, studies on liquid biopsy in breast cancer, colorectal cancer, and NSCLC are compared focusing on ctDNA., Competing Interests: Declarations. Conflict of interest: TM: speakers’ bureau from Chugai Pharmaceutical, KM: speakers’ bureau and research funding from Chugai Pharmaceutical, KA: honoraria from Chugai Pharmaceutical, EB: honoraria and research funding from Chugai Pharmaceutical. All the other authors have no conflict of interest. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)