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Background: In patients with slow-flow vascular malformations (SFVMs) including venous malformations (VM), lymphatic malformations (LM) or Klippel-Trenaunay Syndrome (KTS), somatic gain-of-function mutations in genes encoding phosphatidyl inositol 3-kinase alpha (PI3Kα, gene name PIK3CA) have been identified. A phase 2 study was conducted with the patients to assess the efficacy and safety of ART-001 (serabelisib), an orally available selective PI3Kα inhibitor., Methods: This is a multicenter, randomized, double-blind, proof-of-concept, phase 2 trial. Eligible participants were patients aged 2 years and older, diagnosed either with VM, LM or KTS. Participants were administered either 50 or 100 mg of ART-001 for 24 weeks. The primary endpoint was the response rate defined as the proportion of participants who achieved ≥ 20% reduction in lesion volume at week 24. Secondary endpoints include safety, pharmacokinetics, pain, and quality of life scores., Results: Thirty-five patients (median age: 14 years old; VM, n = 17, KTS, n = 13 and LM, n = 5) were randomly assigned and received treatment (50 mg, n = 17 and 100 mg, n = 18). ART-001 showed a response rate: 29.4% (95% confidence interval 10.3-56.0%) at 50 mg and 33.3% (13.3-59.0%) at 100 mg. Mean lesion volume reductions at 50 mg and 100 mg were - 2.3% (95% CI - 14.3 to 9.6%) and - 12.6% (- 25.3 to 0.06%), respectively. No drug-related serious adverse events were observed. Treatment-emergent adverse events were generally mild to moderate and transient. Pharmacokinetic profiles were similar between pediatric and adolescent/adult patients except for lower C trough levels in pediatric patients., Conclusion: ART-001 was effective and well-tolerated in patients with SFVMs. These results support the further development of ART-001 in SFVMs and other PIK3CA-related overgrowth syndromes to confirm clinical benefits and long-term safety., Trial Registration:  Japan Registry of Clinical Trial, jRCT2071210027. Registered May 25 2021, https://jrct.niph.go.jp/en-latest-detail/jRCT2071210027., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol, amendments, subject-informed consent and informed assent were approved by the independent institutional review board of each study site (Gifu University Hospital, National Center for Child Health and Development, Kobe University Hospital, Oita University Hospital, Keio University Hospital, Juntendo Urayasu Hospital, Tohoku University Hospital, and Tokai University Hospital). After having been explained the clinical trial by the investigator or sub-investigator, signed informed consent was obtained either from participants (age ≥ 20), participants and their parent/guardian (20 > age ≥ 16), or participants’ parent/guardian (age < 16). Children 7 to 15 years of age provided written informed assent. Consent for publication: Written informed consent was obtained from the patient for publication of this article and any accompanying images. Competing interests: AT, KK, and HA were employees of ARTham Therapeutics Inc. and HN was the CEO of ARTham Therapeutics. MO, Tai N, AF, Tad N, NU, JO, SH, and TO served as paid adviser to ARTham Therapeutics Inc. Tai N serves as a paid adviser to Kaken Pharmaceutical Co. Ltd. AF has received honoraria from Nobelpharma Co. Ltd., (© 2025. The Author(s).)

Human African trypanosomiasis (HAT) is one of the most lethal of the neglected tropical diseases. While the discovery of a novel antitrypanosomal drug is highly desired, the creation of a superior lead compound is challenging. Herein we report ukabamide ( 1 ), which was isolated from a marine Moorena sp. cyanobacterium, as a selective and potent antitrypanosomal lipopeptide (IC 50 = 34 ± 18 nM against Trypanosoma brucei rhodesiense ). Its structure was elucidated by spectroscopic analyses and degradation reactions and confirmed by total synthesis. In addition, we prepared two modified analogs and revealed the importance of the fatty acid chain length for biological activity. These findings may provide design guidelines for an antitrypanosomal drug.

Interventional oncology provides image-guided therapies, including transarterial tumor embolization and percutaneous tumor ablation, for malignant tumors in a minimally invasive manner. As in other medical fields, the application of artificial intelligence (AI) in interventional oncology has garnered significant attention. This narrative review describes the current state of AI applications in interventional oncology based on recent literature. A literature search revealed a rapid increase in the number of studies relevant to this topic recently. Investigators have attempted to use AI for various tasks, including automatic segmentation of organs, tumors, and treatment areas; treatment simulation; improvement of intraprocedural image quality; prediction of treatment outcomes; and detection of post-treatment recurrence. Among these, the AI-based prediction of treatment outcomes has been the most studied. Various deep and conventional machine learning algorithms have been proposed for these tasks. Radiomics has often been incorporated into prediction and detection models. Current literature suggests that AI is potentially useful in various aspects of interventional oncology, from treatment planning to post-treatment follow-up. However, most AI-based methods discussed in this review are still at the research stage, and few have been implemented in clinical practice. To achieve widespread adoption of AI technologies in interventional oncology procedures, further research on their reliability and clinical utility is necessary. Nevertheless, considering the rapid research progress in this field, various AI technologies will be integrated into interventional oncology practices in the near future., Competing Interests: Declarations. Conflict of interest: Y.M. received a grant and lecturer fee from Canon Medical Systems outside the submitted work. The other authors have no relevant financial or non-financial interests to disclose. Ethical approval. Ethical approval was not required for this review., (© 2024. The Author(s).)

Objective: To evaluate the effect and safety of sclerotherapy in patients with difficult-to-resect venous malformations treated with ethanolamine oleate., Design and Setting: This investigator-initiated clinical trial employed a multicenter, single-arm design and was conducted in Japan., Patients: Overall, 44 patients with difficult-to-resect venous malformations were categorized into two cohorts: 22 patients with cystic-type malformations and 22 patients with diffuse-type malformations, including children (<15 years old)., Interventions: Adult patients received injections of 5% ethanolamine oleate solution, double diluted with contrast or normal saline, with a maximum dose of 0.4 mL/kg. The same method of administration was used for children (<15 years old). The maximum volume of the prepared solution in one treatment was 30 mL., Evaluation Methods: Treatment effect was assessed by evaluating the difference in lesion volume using magnetic resonance imaging as a primary endpoint and differences in pain using a visual analog scale as a key secondary endpoint., Results: Among the 45 patients who consented, one was excluded owing to potential intracranial involvement of venous malformations during screening. Regarding the primary outcome, 26 of 44 patients (59.1%, 95% confidence interval: 44.41-72.31%) achieved ≥ 20% reduction in malformation volume, with 16 patients having cystic lesions (72.7%, 51.85-86.85%) and 10 patients having diffuse lesions (45.5%, 26.92-65.34%). Both cohorts showed significant improvement in self-reported pain scores associated with lesions 3 months post-sclerotherapy. No death or serious adverse events occurred. Hemoglobinuria was observed in 23 patients (52%), a known drug-related adverse event. Prompt initiation of haptoglobin therapy led to full recovery within a month for these patients., Conclusions: Ethanolamine oleate shows potential as a therapeutic sclerosing agent for patients with difficult-to-resect venous malformations., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Fuji Chemical Industries Co., Ltd. provided ethanolamine oleate for treatment during the study period. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2025 Ozaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/Objectives: The therapeutic efficacy of percutaneous sclerotherapy (PS) for venous malformations (VMs) based on volumetric magnetic resonance imaging (MRI) measurements and its association with early post-treatment coagulation markers remains unexplored. This study evaluates the therapeutic efficacy of 5% monoethanolamine oleate (EO)-based PS in treating difficult-to-resect VMs using volumetric MRI and investigates its association with early changes in coagulation markers. Methods: This post-hoc analysis utilized data from a prospective, open-label, multicenter clinical trial initiated on 1 January 2021. The correlation between MRI-determined volume reduction and post-sclerotherapy changes in coagulation markers was assessed. Results: Between January 2021 and April 2023, 44 patients underwent EO-based PS. Based on a ≥ 20% VM volume reduction, patients were classified into "achieved" ( n = 26; 59.1%) and "non-achieved" ( n = 18; 40.9%) groups. D-dimer levels significantly increased on postoperative day 1 (POD1) compared with pretreatment screening ( p < 0.001), whereas fibrinogen and prothrombin international normalized ratio levels remained unchanged. In the achieved group, a significant correlation was observed between the volume reduction rate and the administered EO dose per lesion volume (mL/cm 3 ; Spearman's ρ = 0.43, p = 0.03). The non-achieved group showed significantly higher D-dimer elevation than the achieved group ( p = 0.03). Conclusions: This is the first multicenter study to evaluate EO-based PS efficacy for VMs using volumetric MRI and explore its relationship with early post-treatment coagulation markers. Elevated D-dimer levels on POD1 were not predictive of treatment efficacy, highlighting their limited clinical utility in assessing therapeutic response.

Ventricular tachycardia (VT) is a severe arrhythmia commonly treated with implantable cardioverter defibrillators, antiarrhythmic drugs and catheter ablation (CA). Although CA is effective in reducing recurrent VT, its impact on survival remains uncertain, especially in patients with extensive scarring. Stereotactic arrhythmia radioablation (STAR) has emerged as a novel treatment for VT in patients unresponsive to CA, leveraging techniques from stereotactic body radiation therapy used in cancer treatments. Recent clinical trials and case series have demonstrated the short-term efficacy and safety of STAR, although long-term outcomes remain unclear. Imaging techniques, such as electroanatomical mapping, contrast-enhanced magnetic resonance imaging and nuclear imaging, play a crucial role in treatment planning by identifying VT substrates and guiding target delineation. However, challenges persist owing to the complex anatomy and variability in target volume definitions. Advances in imaging and artificial intelligence are expected to improve the precision and efficacy of STAR. The exact mechanisms underlying the antiarrhythmic effects of STAR, including potential fibrosis and improvement in cardiac conduction, are still being explored. Despite its potential, STAR should be cautiously applied in prospective clinical trials, with a focus on optimizing dose delivery and understanding long-term outcomes. Collaborative efforts are necessary to standardize treatment strategies and enhance the quality of life for patients with refractory VT., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Gold (or electrum) in hydrothermal fluid precipitates directly from gold sulfide complex and/or partly via suspended nanoparticles. The hydrothermal fluid contains "invisible gold" that is atomically dispersed in sulfide minerals or as nanoparticles with a size of less than 10 nm. However, the contribution of these gold nanoparticles to the formation of native gold and its alloy with silver (electrum) remains unclear. The Higashi-Aogashima Knoll Caldera hydrothermal field, south of Tokyo, Japan, is an area of significant seafloor hydrothermal activity that is known for high-grade gold-containing minerals in sulfide-rich rocks. In this study, dry-polished thin sections were created to minimize sample damage and scanning and transmission electron microscopy were used to investigated the cross-sectional and three-dimensional morphologies of native gold grains in a sulfide-rich mound rock from the Central Cone site of the caldera. The surfaces of the gold grains comprised nanoparticles with sizes of 5-50 nm that were also attached to their periphery, which suggests that gold nanoparticles in deep-sea hydrothermal fluid were involved in the mineralization of the gold. In addition, the distribution of silver was uneven within the gold grains, which suggests that the gold precipitation comprised multiple stages at different temperatures that resulted in the post-deposition or secondary remobilization of silver., Competing Interests: The authors declare no competing interest., (Copyright: © 2025 Okada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Euodia Fruit is a crude drug used to treat migraine and headaches and is well-known to contain indole alkaloids, which may contribute to the observed pharmacological activities. A methanolic extract of Euodia Fruit exhibited pancreatic lipase inhibitory activity (IC 50 13.9 mg/mL). Bioassay-guided fractionation of the extract led to the isolation of 14 quinolone alkaloids (1-14), three indole alkaloids: rutaecarpine (15), evodiamine (16), and dehydroevodiamine (17), and a limonoid: rutaevine acetate (18), among which three quinolone alkaloids (12-14) have been previously undescribed. The structures of 12-14 were determined by extensive spectroscopic analyses, including two-dimensional (2D) NMR. Compounds 2, 3, 6-9, 13, and 14 exhibited pancreatic lipase inhibitory activity, with IC 50 values ranging from 1.40 to 7.37 mM. The results revealed that the length of the aliphatic side chain and the presence of an olefinic bond at the C-2 side chain of the quinolone alkaloids could impact lipase inhibitory activity. In soybean oil-loaded mice, orally administered evocarpine (8) reduced serum triglyceride levels in a dose-dependent manner. Furthermore, 8-14 at 5.0 and 50 μM exhibited peroxisome proliferator-activated receptor (PPAR)-γ ligand-binding activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Due to the growing medical need for gynecologic robotic surgery, several robotic surgeries may be performed in a single day at high-volume centers. This study evaluated the safety of performing multiple robot-assisted hysterectomies (RAHs) per day by the same surgeon., Methods: We reviewed the clinical data of patients who underwent robotic surgery from April 2018 to September 2024 at the Department of Gynecology, Yamanashi Central Hospital, and also examined the surgical type, order, and surgeon for each procedure., Results: A total of 352 RAHs performed by the same surgeon were included. Among them, 267 were the first and second cases performed on the same day (Group A), and 85 were the third to fifth cases (Group B). There were no statistically significant differences between the two groups regarding age, body mass index, uterine weight, surgical indication, and history of abdominal surgery. The median operative time of 68 (35-179) min in Group A and 66 (37-187) min in Group B was similar (p = 0.141). Both groups also had similar estimated blood loss (p = 0.744). Each group had two perioperative complications, and no patient underwent conversion to open or laparoscopic surgery., Conclusion: Performing multiple RAHs by the same surgeon in a single day may be a safe procedure with no negative impact on operative time, blood loss, or perioperative complications. Hence, it could be a useful treatment option for high-volume centers., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

The PARP inhibitor olaparib is an anti-cancer agent based on synthetic lethality that targets poly (ADP-ribose) polymerases. It is used as a therapeutic agent for breast, ovarian, pancreatic, and prostate cancers carrying BRCA1/2 mutations that cause deficiency in homologous recombination. In recent years, acquired resistance to PARP inhibitors has become a clinical problem in PARP inhibitor-treated patients. Meanwhile, the development of molecular targeted drugs for highly malignant oral cancers has not progressed, and effective treatment strategies are needed. In this study, we identified the histone deacetylase inhibitor NSC-3852 as a compound that synergistically enhances the effects of olaparib in oral squamous cell carcinoma cell lines. N-Acetyl-l-cysteine treatment partially recovered cell survival after co-treatment with olaparib and NSC-3852. Moreover, the combination of olaparib and NSC-3852 rapidly upregulated γH2AX at 2 h after treatment, and induced S-phase arrest and apoptosis at 24 h after treatment, suggesting that this combination induced apoptosis through accumulation of massive DNA damage. Taken together, these findings demonstrate that NSC-3852 is a sensitizer of olaparib and suggest that the combination of NSC-3852 and olaparib may be a useful therapeutic strategy for homologous recombination-proficient cancers, including cancers with acquired resistance to olaparib and high-grade oral squamous cell carcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)