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Presepsin (soluble CD14 subtype) is a clinically used diagnostic biomarker for sepsis. It is secreted into the blood by activated macrophages, and serum concentrations are elevated in patients with sepsis. Previous reports suggest that presepsin may be secreted into the peripheral blood due to increased hemophagocytosis. However, the relationship between serum presepsin concentration and hemophagocytosis, as evidenced by bone marrow aspiration for diagnosing hemophagocytic lymphohistiocytosis, is not well understood. Therefore, we investigated the relationship between serum presepsin level and hemophagocytes in bone marrow. We retrospectively analyzed 61 patients with serum presepsin level who underwent bone marrow aspirations. We examined the relationship between serum presepsin level and other laboratory findings, including the number of macrophages and the percentage of hemophagocytes in their bone marrow. Macrophages and hemophagocytes were counted using bone marrow smears. Immunostaining of bone marrow aspirate smears was performed using a CD14 antibody to evaluate the relationship between serum presepsin level and hemophagocytes in the bone marrow. Serum presepsin level correlated with inflammatory markers (C-reactive protein and D-dimer) and markers related to hemophagocytosis (lactate dehydrogenase, ferritin, red blood cell count, hemoglobin, hematocrit, number of macrophages, and percentage of hemophagocytes in the bone marrow). The percentage of hemophagocytes in the bone marrow was positively correlated with serum presepsin level (r = 0.435, p < 0.001) and with ferritin (r = 0.438, p = 0.015), both of which were elevated during hemophagocytosis. CD14 expression is attenuated in hemophagocytes in bone marrow and lymph nodes. These findings suggest that serum presepsin is released by hemophagocytes and reflects the activation of macrophages and hemophagocytosis in bone marrow.

ObjectivesOsteoarthritis (OA) features ageing-related defects in cellular homeostasis mechanisms in articular cartilage. These defects are associated with suppression of forkhead box O (FoxO) transcription factors. FoxO1 or FoxO3 deficient mice show early onset OA while FoxO1 protects against oxidative stress in chondrocytes and promotes expression of autophagy genes and the essential joint lubricant proteoglycan 4 (PRG4). The objective of this study was to identify small molecules that can increase FoxO1 expression.MethodsWe constructed a reporter cell line with FoxO1 promoter sequences and performed high-throughput screening (HTS) of the Repurposing, Focused Rescue and Accelerated Medchem (ReFRAME) library . Hits from the HTS were validated and function was assessed in human chondrocytes, meniscus cells and synoviocytes and following administration to mice. The most promising hit, the histone deacetylase inhibitor (HDACI) panobinostat was tested in a murine OA model.ResultsAmong the top hits were HDACI and testing in human chondrocytes, meniscus cells and synoviocytes showed that panobinostat was the most promising compound as it increased the expression of autophagy genes and PRG4 while suppressing the basal and IL-1β induced expression of inflammatory mediators and extracellular matrix degrading enzymes. Intraperitoneal administration of panobinostat also suppressed the expression of mediators of OA pathogenesis induced by intra-articular injection of IL-1β. In a murine OA model, panobinostat reduced the severity of histological changes in cartilage, synovium and subchondral bone and improved pain behaviours.ConclusionPanobinostat has a clinically relevant activity profile and is a candidate for OA symptom and structure modification.

Gene expression imbalances were measured for tyrosine kinase ( TK ) genes using Nanostring in 19 samples of inflammatory myofibroblastic tumor (IMT). All cases were immunohistochemically stained with anaplastic lymphoma kinase (ALK) and pan-tropomyosin-related-kinase (pan-Trk) antibodies. Five cases with imbalanced ALK expression, reported with Nanostring, were tested using fluorescence in situ hybridization (FISH); two cases with imbalanced neurotrophic tyrosine receptor kinase 3 ( NTRK3 ) expression were tested using reverse transcription-polymerase chain reaction (RT-PCR). One case with imbalanced expression for ROS proto-oncogene 1 ( ROS1 ) was tested using RNA sequencing and RT-PCR. TK fusions were detected in all cases with imbalanced TK expression. RNA sequencing detected a FN1–ROS1 fusion gene in an adult IMT case. IMT with ALK rearrangement showed myofibroblast-dominant features. IMT with ETV6–NTRK3 fusion showed prominent lymphoplasmacytic infiltration with scattered myofibroblasts. Pan-Trk IHC revealed only scattered positively stained cells in IMT with ETV6–NTRK3 fusion gene. ROS1 -positive IMT showed myofibroblast-dominant features.

This paper proposes a cluster-based flight path construction method for automated drone-assisted pear pollination systems in orchard environments. The approach uses RGB-D (Red-Green-Blue-Depth) sensing through an observation drone equipped with RGB and depth cameras to detect blooming pear flowers. Flower detection is performed using a YOLO (You Only Look Once)-based object detection algorithm, and three-dimensional flower positions are estimated by integrating depth information with the drone’s positional and orientation data in the east-north-up coordinate system. To enhance pollination efficiency, the method applies the OPTICS (Ordering Points To Identify the Clustering Structure) algorithm to group detected flowers based on spatial proximity that correspond to branch-level distributions. The cluster centroids then construct a collision-free flight path, with offset vectors ensuring safe navigation and appropriate nozzle orientation for effective pollen spraying. Field experiments conducted using RTK-GNSS-based flight control confirmed the accuracy and stability of generated flight trajectories. The drone hovered in front of each flower cluster and performed uniform spraying along the planned path. The method achieved a fruit set rate of 62.1%, exceeding natural pollination at 53.6% and compared to the 61.9% of manual pollination. These results demonstrate the effectiveness and practicability of the method for real-world deployment in pear orchards.

Introduction Comprehensive analyses using clinical sequences subcategorized osteosarcoma (OS) into several groups according to the activated signaling pathways. Mutually exclusive co-occurrences of gene amplification (PDGFRA/KIT/KDR, VEGFA/CCND3, and MDM2/CDK4) have been identified in approximately 40% of OS, representing candidate subsets for clinical evaluation of additional therapeutic options. Thus, it would be desirable to evaluate the specific gene amplification before starting therapy in patients with OS. Materials and Methods This is a retrospective study. We examined 13 cases of clinical OS samples using NanoString-based copy number variation (CNV) analysis. Decalcification and chemotherapeutic effects on this analysis were also assessed. Results First, the accuracy of this system was validated by showing that amplification/deletion data obtained from this system using various types of cancer cell lines almost perfectly matched to that from the Cancer Cell Line Encyclopedia (CCLE). We identified potentially actionable alterations in CDK4/MDM2 amplification in 10% of samples and potential additional therapeutic targets (PDGFRA/KIT/KDR and VEGFA/CCND3) in 20% of samples, which is consistent with the reported frequencies. Furthermore, this assay could identify these potential therapeutic targets regardless of the sample status (frozen vs formalin-fixed paraffin-embedded [FFPE] tissues). Conclusion We established a NanoString-based rapid and cost-effective method with a short turnaround time (TAT) to examine gene amplification status in OS. This CNV analysis using FFPE samples is recommended where the histological evaluation of viable tumor cells is possible, especially for tumors after chemotherapy with higher chemotherapeutic effects.

Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase ( KIT ) or platelet-derived growth factor receptor alpha ( PDGFRA ). Recently, the neurotrophic tyrosine receptor kinase ( NTRK ) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit. Interestingly, all of these cases showed only trkB but not trkA/trkC expression. Cap analysis of gene expression (CAGE) analysis identified increased number of genes whose promoters were activated in pan-trk/trkB positive GISTs. Imbalanced expression of NTRK2 , which suggests the presence of NTRK2 fusion, was not observed in any of trkB positive GISTs, despite higher mRNA expression. TrkB expression was found in duodenal GISTs and more than half of small intestinal GISTs, and this subset of cases showed poor prognosis. However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.

Background Diffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing Creutzfeldt–Jakob disease (CJD). Thalamic lesions are rarely detected by DWI in sporadic CJD (sCJD) cases with methionine homozygosity at polymorphic codon 129 (129MM) of the prion protein (PrP) gene. Here, we describe an unusual sCJD case, characterized by prolonged isolated thalamic diffusion hyperintensities and atypical brain pathology, in combination with the 129MM genotype. Case presentation A 72-year-old Japanese man developed a mild unsteady gait that had persisted for 1 year. DWI revealed isolated thalamic diffusion hyperintensities. Over the following 4 years, his condition progressed to include ataxia and cognitive decline. Repeated cerebrospinal fluid tests were negative for 14-3-3 protein, total tau protein, and real-time quaking-induced conversion assay. Electroencephalography did not show periodic sharp wave complexes or generalized periodic discharges. Despite these findings, thalamic DWI abnormalities persisted and evolved to include cortical lesions in the later stage of the disease. Genetic testing confirmed a 129MM genotype with no pathogenic PrP gene variants. Brain autopsy identified type 2 pathogenic PrP and the absence of the M2-thalamic prion strain, suggesting an MM2-cortical (MM2C)-subtype of sCJD. Histopathology revealed small vacuoles (sv) and patchy-perivacuolar PrP deposits without large vacuoles (lv). Patchy-perivacuolar deposits are a characteristic feature of the MM2C (lv) subtype and indicate MM2C (lv) pathology. Thus, this case was classified as a rare MM2C (sv + lv) subtype. No PrP protein staining was observed in the thalamus, despite spongiform changes with small vacuoles. Conclusions This case underscores the diagnostic challenges of atypical CJD with isolated thalamic abnormalities on DWI. Despite negative cerebrospinal fluid findings and clinical diagnostic criteria, persistent DWI abnormalities and evolving clinical symptoms continued to raise suspicion of CJD. A definitive diagnosis, being the MM2C (sv + lv) subtype of sCJD, was confirmed upon pathological examination. Even when atypical findings, such as isolated thalamic abnormalities, are observed and various tests are negative, if suspicion of CJD cannot be ruled out, it is important to confirm the diagnosis and pathological subtypes via postmortem analysis.

Stable pear cultivation relies on cross-pollination, which typically depends on insects or wind. However, natural pollination is often inconsistent due to environmental factors such as temperature and humidity. To ensure reliable fruit set, artificial pollination methods such as wind-powered pollen sprayers are widely used. While effective, these methods require significant labor and operational costs, highlighting the need for a more efficient alternative. To address this issue, this study aims to develop a fully automated drone-based pollination system that integrates Artificial Intelligence (AI) and Unmanned Aerial Vehicles (UAVs). The system is designed to perform artificial pollination while maintaining conventional pear cultivation practices. Demonstration experiments were conducted to evaluate the system’s effectiveness. Results showed that drone pollination achieved a fruit set rate comparable to conventional methods, confirming its feasibility as a labor-saving alternative. This study establishes a practical drone pollination system that eliminates the need for wind, insects, or human labor. By maintaining traditional cultivation practices while improving efficiency, this technology offers a promising solution for sustainable pear production.