Daido University

Abstract Background: Tumor-infiltrating lymphocytes (TILs) reflect host immune response and are associated with prognosis and treatment response in HER2-positive and triple-negative breast cancer (TNBC). While the International Immuno-Oncology Biomarker Working Group recommends evaluating stromal TILs in tumor areas, intratumoral heterogeneity and small sample size in core needle biopsy (CNB) specimens limit consistent assessment. It remains unclear whether central tumor (CT) or invasive margin (IM) regions should be prioritized and what cut-off values are clinically relevant. Ultrasonographic (US) features may also reflect the immune microenvironment. We previously proposed a TILs-US score based on three US features that predicts lymphocyte-predominant breast cancer (LPBC). This study evaluated the clinical utility of TILs assessment from CT and IM regions, appropriate cut-off values for predicting response in HER2-positive and TNBC using CNB, and explored optimal biopsy targeting through pathologic and US comparisons. Methods: In this multicenter retrospective study, we analyzed 239 patients (124 HER2-positive, 115 TNBC) with cT1-3/cN0-2 breast cancer who underwent surgery after neoadjuvant chemotherapy (NAC). TILs were evaluated using CNB specimens obtained before NAC and assessed separately in the central tumor (CT) and invasive margin (IM) regions. The IM was defined as a 1-mm-wide area centered on the interface between the tumor and surrounding stroma, while the CT was defined as the remaining intratumoral area within the IM boundary. TILs were analyzed using binary cut-offs of 30% and 50%, as well as a three-tier classification: low (0-10%), intermediate (11-49%), and high (≥50%). Pre-treatment ultrasound (US) findings included tumor shape (scored 0-2), internal echo (0-2), and posterior echo (0-3), which were used to calculate a composite TILs-US score ranging from 0 to 7. Associations between TIL levels, US features, and pathological complete response (pCR) were analyzed. Results: Overall, 104 patients achieved pCR (HER2-positive: 39; TNBC: 65). Using a 30% cut-off, TILs were evenly distributed both CT and IM, while ≥50% cases were relatively rare especially CT (CT: 10%; IM: 20%). CT TILs ≥30% was significantly associated with pCR (p=0.001), whereas the ≥50% cut-off was not (p=0.128). In contrast, both 30% and 50% cut-offs in the IM region were predictive of pCR (p<0.001 and p=0.009, respectively). Subtype analysis revealed that in TNBC, TILs ≥30% in both CT and IM regions were significantly correlated with pCR. In HER2-positive cases, however, only IM TILs ≥30% was predictive of pCR. Similar trends were observed with the three-tier classification. Among US features, a small lobulated shape was associated with high TILs levels in both CT and IM regions, while an enhanced posterior echo was correlated with high TILs in the IM region. Conclusion: Our findings suggest that TILs assessment should include the IM in addition to the CT, especially in CNB specimens as provide valuable information. Given the limited tissue area available in CNB specimen, using a 30% cut-off for TILs may offer a clinically meaningful threshold to predict treatment response. In cases where US findings suggest central fibrosis, targeting only the tumor center may result in sampling fibrotic areas with sparse immune and tumor cells, potentially hindering proper evaluation. Therefore, selecting the biopsy target based on US imaging is essential. Especially in HER2-positive breast cancer, as well as TNBC, it is important for operators to consider the optimal needle insertion angle and sampling site to ensure appropriate sampling of viable tumor tissue and immune microenvironment for accurate pathological and immunological evaluation. Citation Format: Y. Kimura, R. Yamaguchi, K. Fukui, A. Kanou, M. Noma, S. Akashi-Tanaka, K. Arihiro, N. Iwamoto, Y. Ohta, T. Okuno, S. Kashiwagi, Y. Kamei, Y. Tanada, S. Nakano, A. Nagata, A. Murakami, Y. Mochitomi, A. Yamakawa, M. Yamaguchi, H. Shima, A. Emi. Ultrasound-guided biopsy-based tils assessment at tumor margins as a predictive biomarker of neoadjuvant treatment response in early her2-positive and triple-negative breast cancer: a multicenter study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-18.

Despite substantial advances in understanding urinary stone formation, including mechanisms of calcium phosphate (CaP) crystallization, tissue infiltration, and stone development via Randall’s plaques, the global prevalence of urolithiasis continues to rise and current knowledge has only limited impact on clinical outcomes. This study focuses on the CaP phase, particularly brushite, and re-examines its role under physiologically relevant conditions as a potential key to more effective prevention. The aim was to elucidate how reactions proceed near the surfaces of brushite crystals that can present in urine, and how these reactions are modulated by coexisting proteins, using wide-field optical observation combined with quantitative modeling. Single-crystal brushite was immersed in a model solution pre-equilibrated with calcium oxalate monohydrate (COM), and the time evolution of the Ca2+ concentration field associated with brushite dissolution was evaluated by in situ microscopy and one-dimensional diffusion analysis. The results demonstrated that brushite dissolution generates a critical Ca2+ supersaturation zone extending several hundred micrometers from the crystal surface, within which COM nucleation occurs. Upon addition of bovine serum albumin (BSA) as a model protein, the average growth of COM was inhibited, whereas the local frequency of COM nucleation increased markedly in regions of the brushite surface with high step and kink densities, yielding dense, rigid COM–brushite composites. These findings indicate that brushite crystals function not merely as apatite precursors, but as localized “reaction fields” that spatially control calcium oxalate nucleation, aggregation, and consolidation. Furthermore, urinary proteins can, through these fields, act not only as inhibitors but also as local promoters of stone formation.

The aerial acrobat robot is a mechanical structure that achieves continuous acrobatic motion without electrical power by utilizing gravitational potential energy.The power of this motion is the rotational motion resulting from the imbalance of moments caused by both the masses, called counterbalance, and the weight of the robot. Or, it is the rotational motion resulting from the reciprocal energy conversion between the gravitational potential and kinetic energy of these two masses. Using the quasi-static single-link model mechanism, we derived a formula for the power moment that is important in the design of the mechanical structure to produce the aerial acrobat robot’s motion. This structure is mainly made of resin and is approximately 2 m long. Based on this structure, we developed a paper craft aerial acrobat robot compacted to about 0.27 m so that anyone can easily play with it. In the paper craft aerial acrobat robot based on the quasi-static single-link model, instability in the rotational behavior becomes apparent. To enhance the accuracy of the analysis of rotational moments, which are crucial in design, we develop a modeling method for a paper craft aerial acrobat robot using multibody dynamics. Furthermore, the theoretical solution for a simplified model of the paper craft aerial acrobat robot is constructed based on the double pendulum. The dynamic moments obtained by the modeling method of the paper craft aerial acrobat robot is verified by comparing the theoretical solution.

Secondary-air injection has previously been proposed as a means of mitigating the pressure oscillations that can arise during high-load homogeneous charge compression ignition (HCCI) combustion. The present work clarifies how the suppression effect changes when the air is introduced from multiple locations. HCCI experiments were carried out in a rapid-compression machine using one, two, or four wall-mounted gas injectors, while injection pressure and duration were also varied systematically. Over the entire test matrix, the oscillation intensity decreased monotonically with injector count: at a given injection pressure or duration, more injectors produced weaker pressure swings. When the data were reorganized by the total volume of injected air, multi-point injection still required a smaller air dose to achieve the same level of suppression: two injectors halved the air demand relative to a single injector, and four injectors reduced it further. Infrared thermometry revealed that low-intensity cases featured a complex, interlaced temperature field in which hot kernels emerged simultaneously at several sites and spread throughout the chamber. Such a distributed ignition pattern was realized with shorter pulses and smaller air quantities as the number of injectors increased, explaining the enhanced suppression. The findings deepen the understanding of combustion-oscillation dynamics in HCCI engines and provide quantitative guidance for optimizing secondary-air injection systems.

Weak soils present significant challenges for highway construction in seismic regions, often leading to instability issues such as settlements and slope failures. These conditions necessitate safe, effective, and cost-efficient solutions to ensure embankment stability. Despite the critical importance of embankment stability under dynamic loading, research on soil reinforcement techniques in seismic scenarios is limited. This study evaluated the seismic performance of conventional deep cement mixing (DCM) columns versus innovative T-shaped deep mixing (TDM) columns for highway embankments on soft soil through three-dimensional finite element analysis via PLAXIS 3D. After validation, a comprehensive parametric study investigated the effects of column type, spacing (1.67m, 2.14m, and 3.0m), and seismic loading on embankment response parameters, including settlement, lateral displacement, and excess pore water pressure. The results demonstrate that both reinforcement methods significantly enhance seismic stability compared with unreinforced conditions. Compared with unreinforced embankments, TDM columns achieved superior performance, with settlement reductions of 89.95% versus 36.11% for DCM columns. Under seismic loading, the TDM columns exhibited 88.31% less settlement than the DCM columns at the embankment crest. Parametric analysis revealed that closer column spacing (1.67m) reduced settlements to 0.0032m for TDM compared with 0.023m at wider spacing (3.0m). The TDM columns also demonstrated more controlled consolidation behavior with smoother settlement time histories and reduced excess pore water pressure fluctuations. The findings indicate that TDM columns provide superior seismic performance through enhanced load transfer mechanisms and improved soil‒structure interactions, making them the preferred solution for highway embankments in seismically active regions.

Development of efficient catalysts for ammonia production from atmospheric pressure of dinitrogen at ambient tem-perature has been desired for next-generation scientific techniques to achieve a carbon-neutral society. Herein, we report the synthesis and catalytic activity of a new series of molybdenum trichloride complexes with PCP-type pincer ligands bearing benzoimidazole skeletons connected with aryl groups or a naphthoimidazole skeleton, which have been designed as efficient catalysts for reduction of dinitrogen into ammonia, based on our previous computational screening. The large π-conjugated structure of the pincer ligands effectively increased the electron-accepting ability of the molybdenum complexes without compromising their proton-accepting abil-ity, resulting in the promotion of the rate-determining step (i.e., the proton-coupled electron transfer (PCET) to the nitride complexes as a key reaction intermediate) and catalytic activity toward ammonia formation from dinitrogen under ambient reaction conditions. As a result of both theoretical and experimental investigations, the so far highest turnover frequencies for ammonia formation (TOF(NH3), up to 900 equiv./Mo•min−1) and maximum turnover number (TON(NH3), up to 84,000 equiv./Mo) were successfully achieved by using molybdenum complexes with a 3,5-bis(trifluoromethyl)phenyl (ArF) group on the benzoimidazole skeleton because of the synergistic effect of the ArF group, i.e., the extension of the π-conjugation in the ligand and the electron-withdrawing ability.

ObjectiveWe investigated the association between interleukin-6 (IL-6) and interleukin-8 (IL-8) concentrations in bone marrow fluid and osteoporotic vertebral fracture (OVF) prognosis to obtain insights that could improve the prediction of poor prognosis.MethodsPatients with OVFs admitted consecutively to a single facility and who underwent balloon kyphoplasty were prospectively enrolled. Bone marrow fluid was collected during surgery, and IL-6 and IL-8 concentrations were measured. Independent experts blinded to patient details examined the preoperative magnetic resonance imaging (MRI) radiographs to identify poor prognostic findings. IL-6 and IL-8 levels in the groups with and without poor prognostic findings were compared using the Wilcoxon rank-sum test. Associations between log-transformed IL-6 and IL-8 levels and poor prognosis were evaluated using logistic regression with adjustments for confounding factors.ResultsAmong the 95 enrolled patients, 49 were excluded, and 46 were included in the analysis. In the poor prognosis group, both IL-6 and IL-8 levels were higher than those in the non-poor prognosis group (median IL-6: 491 vs. 72 pg/mL, p=0.014; median IL-8: 1574 vs. 84 pg/mL, p=0.003). Associations between log-transformed IL-6 and IL-8 concentrations and poor prognosis were observed, with crude and adjusted odds ratios for IL-6 at 1.75 (95% confidence interval (CI) 1.10-2.81) and 1.95 (95% CI 1.05-3.63), respectively, and for IL-8 at 1.81 (95% CI 1.23-2.65) and 2.10 (95% CI 1.21-3.64), respectively.ConclusionIL-6 and IL-8 concentrations in the bone marrow fluid may be associated with poor OVF prognosis. Their causal roles and potential as serum prognostic markers require further investigation.

<bold>Introduction:</bold> In sarcoidosis, the inflammatory subset of CD14+/CD16+ intermediate monocytes (IM) has been found to correlate with disease severity and prognosis. We assessed the percentage of IM in treatment naïve patients with pulmonary sarcoidosis during their treatment with methotrexate (MTX) or prednisone as exploratory endpoint of the PREMDETH trial. <bold>Method</bold> Monocytes were measured by FACS in whole blood and IM were identified. Mann-Whitney U tests were used to test for differences between groups. <fig><object-id>erj;66/suppl_69/PA5131/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><caption> Figure 1 Mean (±95%CI) percentage of IM monocytes over time. *** p<0.001. </caption><graphic></graphic></fig> <bold>Results:</bold> During treatment with MTX there was no change in percentage of IM over the course of 24 weeks. In patients treated with prednisone percentage of IM decreased significantly, resulting in a median change of -61% at 4 weeks, -50% at 16 weeks and -42% at 24 weeks (p <0.001, <0.001 and 0.001). At 4, 16 and 24 weeks mean percentage of IM was significantly different between MTX and prednisone (Fig. 1). <bold>Conclusion:</bold> While prednisone and MTX are both anti-inflammatory drugs and equipotent in improving FVC after 24 weeks of treatment of patients with pulmonary sarcoidosis during the PREDMETH trial, there is a remarkable difference in levels of circulating IM between both drugs. Our data suggests that compared to prednisone, the anti-inflammatory effect of MTX in patients with sarcoidosis does not involve an effect on the IM monocytes in the peripheral circulation.

BACKGROUNDAnaplastic ependymomas are malignant CNS tumors with poor prognosis. Chondroid metaplasia in ependymomas is extremely rare, and its clinical significance remains unclear.OBSERVATIONSA 21-year-old male underwent gross-total resection and adjuvant radiotherapy for an anaplastic ependymoma. Over the following 6 years, he experienced multiple recurrences treated with endoscopic resections, Gamma Knife radiosurgery, temozolomide, and bevacizumab. Seven years after initial surgery, a previous irradiated cerebellar lesion showed aggressive regrowth and was resected. Histopathology revealed chondroid metaplasia within the recurrent tumor. Although temporary control of the tumor within the irradiated field with proton therapy was achieved, the rapid progression of disseminated lesions proved fatal.LESSONSThis is the fifth reported case of chondroid metaplasia in an ependymoma following radiotherapy. Once metaplasia occurs, the prognosis is highly unfavorable, particularly in anaplastic cases. Although proton therapy was administered under suboptimal conditions, the initial tumor control suggests it may be more effective if applied earlier. In the absence of effective chemotherapy, repeated minimally invasive surgeries and radiosurgeries may help preserve cognitive function and control disease progression.https://thejns.org/doi/10.3171/CASE25308