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RNA Delivery Using a Graphene Oxide-Polyethylenimine Hybrid Inhibiting Myotube Differentiation
Full text linkGraphene oxide (GO) conjugated with short polyethylenimine (PEI) chains (GO-PEI) has been designed as a candidate nanocarrier for small interfering RNA (siRNA) delivery to mammalian cells based on the efficient interaction between the positively charged GO-based platform and the negatively charged siRNA. The function and efficiency of siRNA delivery using GO-PEI were compared to those using the positive control Lipofectamine RNAiMax by analyzing the differentiation to myotubes, and myogenin gene and protein expression in C2C12 cells. RNAiMax transfection induced cellularization and reduction of both myogenin gene and protein expression, suggesting that the differentiation of C2C12 cells was triggered by gene silencing. While GO-PEI also promoted cellularization, the myogenin gene expression remained comparable to scrambled controls, whereas the protein levels were higher than those observed with RNAiMax. Mechanistically, we attributed the reduced gene silencing efficiency of GO-PEI to a poor endosomal escape, despite strong siRNA complexation. This limitation was likely due to a low buffering capacity of GO-PEI, as a significant fraction of nitrogen atoms were already protonated, reducing the availability of free amines necessary for endosomal disruption. An appropriate chemical modification to enhance siRNA release from the endosomes is therefore essential for advancing the development of GO-based platforms as versatile and efficient nanocarriers in gene therapy applications
An Extension of Input Setup Assistance Service Using Generative AI to Unlearned Sensors for the SEMAR IoT Application Server Platform
Full text linkNowadays, Internet of Things (IoT) application systems are broadly applied to various sectors of society for efficient management by monitoring environments using sensors, analyzing sampled data, and giving proper feedback. For their fast deployment, we have developed Smart Environmental Monitoring and Analysis in Real Time (SEMAR) as an integrated IoT application server platform and implemented the input setup assistance service using prompt engineering and a generative AI model to assist connecting sensors to SEMAR with step-by-step guidance. However, the current service cannot assist in connections of the sensors not learned by the AI model, such as newly released ones. To address this issue, in this paper, we propose an extension to the service for handling unlearned sensors by utilizing datasheets with four steps: (1) users input a PDF datasheet containing information about the sensor, (2) key specifications are extracted from the datasheet and structured into markdown format using a generative AI, (3) this data is saved to a vector database using chunking and embedding methods, and (4) the data is used in Retrieval-Augmented Generation (RAG) to provide additional context when guiding users through sensor setup. Our evaluation with five generative AI models shows that OpenAI’s GPT-4o achieves the highest accuracy in extracting specifications from PDF datasheets and the best answer relevancy (0.987), while Gemini 2.0 Flash delivers the most balanced results, with the highest overall RAGAs score (0.76). Other models produced competitive but mixed outcomes, averaging 0.74 across metrics. The step-by-step guidance function achieved a task success rate above 80%. In a course evaluation by 48 students, the system improved the student test scores, further confirming the effectiveness of our proposed extension
A Guided Self-Study Platform of Integrating Documentation, Code, Visual Output, and Exercise for Flutter Cross-Platform Mobile Programming
Full text linkNowadays, Flutter with the Dart programming language has become widely popular in mobile developments, allowing developers to build multi-platform applications using one codebase. An increasing number of companies are adopting these technologies to create scalable and maintainable mobile applications. Despite this increasing relevance, university curricula often lack structured resources for Flutter/Dart, limiting opportunities for students to learn it in academic environments. To address this gap, we previously developed the Flutter Programming Learning Assistance System (FPLAS), which supports self-learning through interactive problems focused on code comprehension through code-based exercises and visual interfaces. However, it was observed that many students completed the exercises without fully understanding even basic concepts, if they already had some knowledge of object-oriented programming (OOP). As a result, they may not be able to design and implement Flutter/Dart codes independently, highlighting a mismatch between the system’s outcomes and intended learning goals. In this paper, we propose a guided self-study approach of integrating documentation, code, visual output, and exercise in FPLAS. Two existing problem types, namely, Grammar Understanding Problems (GUP) and Element Fill-in-Blank Problems (EFP), are combined together with documentation, code, and output into a new format called Integrated Introductory Problems (INTs). For evaluations, we generated 16 INT instances and conducted two rounds of evaluations. The first round with 23 master students in Okayama University, Japan, showed high correct answer rates but low usability ratings. After revising the documentation and the system design, the second round with 25 fourth-year undergraduate students in the same university demonstrated high usability and consistent performances, which confirms the effectiveness of the proposal
Two Cases of Esophageal Mucosal Damage Observed after Peroral Endoscopic Myotomy for Esophageal Motility Disorders
Full text linkThis report presents two cases of esophageal mucosal damage following peroral endoscopic myotomy (POEM) for esophageal motility disorders. In the first case, delayed perforation and mediastinitis occurred on postoperative day 15 and the patient was treated with endoscopic clipping and antibiotics. In the second case, although no perforation was observed, extensive mucosal injury developed the day after POEM which was successfully managed by fasting and antibiotic therapy. These findings highlight the need for careful patient management to minimize the risks associated with POEM, while maximizing its therapeutic benefits
Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates
Full text linkContext: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC).
Objective: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs.
Evidence acquisition: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs).
Evidence synthesis: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo.
Conclusions: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings
A Review of the Endoscopic Treatment for Bile Leak Following Cholecystectomy and Hepatic Surgery
Full text linkBile leak occurs in 2-25% of liver transplant, 3-27% of hepatic resection, and 0.1-4% of cholecystectomy cases. The clinical course of bile leak varies depending on the type of surgery that caused the fistula, as well as the type, severity, and timing of bile duct injury. Although infections resulting from bile leak can be life-threatening, the introduction of endoscopic treatment has enabled some patients to avoid reoperation and has reduced the negative impact on quality of life associated with external fistulas for percutaneous drainage. Endoscopic interventions, such as sphincterotomy and stent placement, reduce the pressure gradient between the bile duct and duodenum, facilitating bile drainage through the papilla and promoting the closure of the leak. We reviewed the literature from 2004 to 2024 regarding bile leak following cholecystectomy and liver surgery, examining recommended techniques, timing, and treatment outcomes. In cases of bile leak following cholecystectomy, clinical success was achieved in 72-96% of cases, while success rates for bile leak following liver surgery ranged from 50% to 100%. Although endoscopic treatment is effective, it is not universally applicable, and its limitations must be carefully considered
Inhibition of Air-Exposure Stress–Induced Autolysis in Clostridium perfringens by Zn2+
Full text linkClostridium perfringens is a pathogenic anaerobe that causes gas gangrene and food poisoning. Although autolysin-mediated reorganization of the bacterial cell wall is crucial for cell division, excessive autolysin activity induced by stressors can lead to cell lysis. In C. perfringens, air exposure is a significant stressor that causes cell lysis, and Acp (N-acetylglucosaminidase) is known to be a major autolysin. To further facilitate C. perfringens research, a technology to prevent air-induced cell lysis must be developed. This study investigated the role of Acp in air-induced autolysis and explored potential inhibitors that would prevent cell lysis during experimental procedures. Morphological analyses confirmed that Acp functions as an autolysin in C. perfringens, as acpdeficient strains exhibited filamentous growth. The mutants exhibited negligible autolysis under air-exposure stress, confirming the involvement of Acp in the autolytic process. We also evaluated the effects of various divalent cations on Acp activity in vitro and identified Zn2+ as a potent inhibitor. Brief treatment with a Zn2+- containing buffer induced dose-dependent cell elongation and autolysis inhibition in C. perfringens. These findings demonstrate that simple Zn2+ treatment before experiments stabilizes C. perfringens cells, reducing autolysis under aerobic conditions and facilitating various biological studies, except morphological analyses
Epstein-Barr Virus-Associated Early Gastric Carcinoma with Lymphoid Stroma Mimicking a Submucosal Tumor: A Typical Case Diagnosed by Endoscopic Resection and Treated by Local Resection with Sentinel Node Navigation
Full text linkGastric cancer with lymphoid stroma (GCLS) accounts for 1%-7% of gastric cancers; ~80% are Epstein-Barr virus (EBV)-positive. The rate of lymph node metastasis is relatively low, even when an early GCLS has invaded the submucosa. We report an early GCLS with massive submucosal invasion mimicking a submucosal tumor (SMT), diagnosed by endoscopic submucosal resection (ESD) and treated with local resection and sentinel node navigation surgery (SNNS). The patient was a 40-year-old Japanese man. A protruding lesion on the greater curvature of the middle part of his stomach was detected by X-ray, and an endoscopic examination revealed a 2.5-cm protruding tumor covered with a normal mucosa and small ulcers at the apex. ESD was performed for a diagnosis. The pathological diagnosis was lymphoepithelioma-like gastric cancer (GCLS), pT1b(SM2), Ly0, V0, pHM1, pVM1. EBV infection in the cancer cells was confirmed pathologically by EBV-encoded RNA. The local resection was performed using SNNS. The patient has had no recurrence or post-gastrectomy syndrome 4 years postsurgery. EBV-associated early GCLS resembling an SMT is relatively rare, and clinicians need to be aware of this disease. Local resection using SNNS may be a surgical option for GCLS cases with a low rate of lymphatic metastasis
Effects of Visual Stimuli on Perceived Sound Volume in Virtual Reality Spaces
No full textWith the proliferation of affordable and high-performance virtual reality (VR) devices, VR content such as games and the metaverse is becoming increasingly widespread. In VR environments, users experience various sensory stimuli, primarily through visual and auditory cues. However, subjective perception of these stimuli varies based on user context. Existing studies have shown that auditory perception can be influenced by visual stimuli, however, most of them have focused on congruent audiovisual stimuli, leaving the effects of non-congruent pairings unexplored. This study investigates how visual stimuli, specifically color and crowdedness, influence perceived sound volume in VR. In the experiment that participants experienced VR environments with different room colors while listening to test tones, the results showed that warm colors led to higher perceived volume at low sound levels. Also, in the experiment that participants viewed VR scenes with varying crowd densities while hearing announcements, less crowded environments resulted in higher perceived sound volume. These findings suggest that visual context impacts auditory perception, providing insights for optimizing hearable devices and enhancing VR auditory experiences
Ti-18Nb-xAl合金の構成相と材料特性に及ぼすAl添加量の影響
Full text linkThe Ti-18mass%Nb alloy with a quenched α” martensitic structure exhibited a high damping capacity. However, there are issues such as lower strength than annealed α+β structure and decreasing damping capacity due to heating until 400 K. Therefore, in this study, to address these issues, we investigated the effect of Al addition on the constituent phases and material properties of Ti-18Nb-xAl alloys. The crystal structure was determined by examining the lattice constant and unit volume using X-ray diffraction, and optical microscopy was also performed. The material properties were investigated by Vickers hardness, Young’s modulus, internal friction, tensile tests, and DSC measurements. Vickers hardness and tensile strength increased with increasing Al content. This is thought to be due to the combined effects of the refinement of the microstructure and solid-solution strengthening due to Al addition. The Young’s modulus increased slightly from 0Al to 1Al, but increased significantly to 4Al. Internal friction was highest for 0Al and decreased for 4Al, whereas 7Al showed a higher value than 1Al. In the DSC heating curves, there was a decrease in the exothermic peak starting temperature and an increase in the phase-transformation heat with the addition of Al, except for 1Al. It was suggested that these changes in Ti-18Nb-xAl alloys were influenced by the structure of the quenched α” phase, texture, and pseudoelasticity or phase transformation by deformation