Houston Medical Center

Abstract Background: Anti-tumor immune activity impacts outcomes in HER2+ EBC, and anti-HER2 antibodies act in part through immune mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC). Margetuximab is an anti-HER2 antibody engineered to enhance ADCC through increased affinity for FcγRIIIa. Early changes in circulating immune populations during anti-HER2 therapy remain poorly characterized. We used CyTOF to profile peripheral blood mononuclear cells (PBMCs) at baseline and early on-treatment in patients receiving neoadjuvant chemotherapy plus HER2-directed therapy. Methods: The investigator-initiated MARGOT trial (NCT04425018/TBCRC052) randomized 171 patients with stage II-III HER2+ EBC 1:2 to receive neoadjuvant THP (trastuzumab/pertuzumab/paclitaxel) or TMP (margetuximab/pertuzumab/paclitaxel). The primary endpoint, pathologic complete response (pCR), was previously reported; pCR was numerically higher with TMP but not statistically significant. This PBMC sub-study included all patients with paired PBMCs at baseline and cycle 2 day 1 (C2D1; 3 weeks on-treatment) from sites meeting quality criteria before the data cut-off. A total of 91 patients (THP n = 25, TMP n = 66) underwent CyTOF profiling at both timepoints using 22 surface and 13 functional markers, identifying 26 immune cell populations. Descriptive statistics were used to summarize baseline and on-treatment cell type changes (Δ). Associations with pCR were evaluated using logistic regression; on-treatment changes by treatment arm were analyzed using linear regression. Multiple testing was addressed using false discovery rate (q-values); raw p-values <0.05 were considered of interest. We hypothesized that ADCC effector populations (e.g., NK cells, monocytes) would change more with margetuximab, and that evidence of ADCC would correlate with response. Results: For the 91 patients (56 HR+, 35 HR-), pCR rates were similar to the overall trial: 52% TMP, 48% THP. Baseline cell types associated with pCR overall and by treatment arm are shown in Table 1. After 3 weeks of therapy, classical monocytes showed the largest change across all cell populations in both treatment arms (mean Δ -5.1% (p<0.001, q<0.001) in TMP and -4.6% (p = 0.013, q = 0.110) in THP). A decrease in one activated NK cell subset (NK CD56dimCD57+CD8-) was observed only with TMP (TMP: mean Δ -1.83% vs THP: mean Δ -0.47%; mean difference TMP vs THP = -1.36; p = 0.002, q = 0.052). Functional marker analyses will be presented at the meeting. Conclusions: Neoadjuvant chemotherapy plus anti-HER2 therapy induces early changes in circulating immune populations in HER2+ EBC. PBMC profiling reveals a rapid decline in circulating monocytes and NK cell subsets after 3 weeks of therapy, potentially reflecting tumor migration and contribution to ADCC. Citation Format: E. Segui, H. Heiling, J. Baginska, A. N. Nau, I. Gomez Diaz, J. Huezo, P. R. Pohlmann, M. F. Rimawi, N. F. Sinclair, R. L. Yung, N. U. Lin, A. C. Wolff, M. K. DeMeo, A. Root, T. Rahman, A. Mohammed-Abreu, M. DiLullo, A. Patel, E. R. Ogayo, T. A. King, E. P. Winer, E. A. Mittendorf, N. Tayob, S. Tolaney, I. E. Krop, J. Agudo, A. G. Waks. Peripheral immune profiling during neoadjuvant HER2-targeted therapy in HER2-positive (HER2+) early breast cancer (EBC): Mass cytometry (CyTOF) analysis from the MARGOT trial [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 PS2-08-10.

Digital twins are increasingly utilized across all lifecycle stages of physical entities. Augmented reality (AR) offers real-time immersion into three-dimensional (3D) data, which provides an immersive experience with dynamic, high-quality, and multi-dimensional digital twins. A robust and customizable data platform is essential to create scalable 3D digital twins; Universal Scene Description (USD) provides these necessary qualities. Given the potential for integrating immersive AR and 3D digital twins, we developed a software application to bridge the gap between multi-modal AR immersion and USD-based digital twins. Our application provides real-time, multi-user AR immersion into USD-based digital twins, making it suitable for time-critical tasks and workflows. AR digital twin software is currently being tested and evaluated in an application we are developing to train astronauts. Our work demonstrates the feasibility of integrating immersive AR with dynamic 3D digital twins. AR-enabled digital twins have the potential to be adopted in various real-time, time-critical, multi-user, and multi-modal workflows.

We propose a workflow for high-resolution velocity inversion and seismic imaging that jointly utilizes OBN and DAS-VSP data. Because DAS-VSP data record axial strain rate and OBN data capture pressure, directly integrating these measurements into a Full Waveform Inversion (FWI) can be challenging. Conventional approaches convert DAS-VSP data into velocity components, relying on assumptions and approximations that may introduce errors. To address this issue, we present a novel method that directly simulates strain rate components using the acoustic wave equation with virtual dipole sources, explicitly accounting for the gauge length effect in DAS measurements. This approach precisely reconstructs the data and avoids errors associated with data conversion as well as gauge length effects. We applied the proposed method to a joint OBN and DAS-VSP survey conducted in the East China Sea. Our results demonstrate that the combined use of OBN and DAS-VSP data reduces parameter trade-offs, furth

The fluid end subsystem in cementing equipment is critical to the reliability and performance of pressure pumping operations. Failures in components such as valves, plungers, and seals can lead to costly downtime and operational risks. This paper presents a lightweight and interpretable anomaly detection method for identifying fluid end anomalies. The approach leverages the deviation between theoretical flow rate calculated from crankshaft speed and actual flow rate measured by a flowmeter to compute a normalized flow rate difference (NFRD). A health indicator is extracted from NFRD per cementing job, and anomalies are detected using a threshold-based classifier. Validation on three cementing pumping units demonstrates the method’s effectiveness, achieving a 66.7% detection rate and 75% precision. The proposed model supports rapid troubleshooting, enhances maintenance planning, and reduces unplanned downtime.

Poor recovery of active glenohumeral external rotation (aGHER) after brachial plexus birth injury (BPBI) is common. Late spinal accessory nerve-to-infraspinatus motor branch (SAN-IS) transfer has been reported as effective. The authors investigated its efficacy in children older than 4 years with BPBI. This case series involved children with no aGHER undergoing SAN-IS transfer. Indications included absent aGHER in shoulder abduction and a positive external rotation drop test. Subscapularis release was done for passive GHER less than 30 degrees in patients without glenohumeral dysplasia, whereas external derotational humeral osteotomy was performed for those with dysplasia and passive GHER less than 0 degrees. Data collected included demographics, Narakas group classification, preoperative and postoperative hand-to-neck Mallet scores, postoperative aGHER, aGHER strength (British Medical Research Council scale), and parental satisfaction. Twenty-six patients, with a mean age of 9.9 years (range, 4 to 26 years) and mean follow-up of 27.9 months (range, 12 to 74 months), were included. Five patients (19%) had a concurrent upper subscapularis release, and 8 (31%) underwent derotational humeral osteotomy. Infraspinatus was macroscopically normal and contractile in all but 2 cases. Twenty-one patients (80%) achieved a mean aGHER of 71 degrees (range, 60 to 80 degress). Of these, 90% scored M4 on the British Medical Research Council scale, and 85% had a hand-to-neck Mallet score of 4. Shoulder forward flexion improved a mean of 35 degrees (range, 20 to 60 degrees) in 40% of patients. Parents were satisfied in 6 cases and extremely satisfied in 20 cases. Late SAN-IS transfer is both effective and safe for restoring aGHER in patients older than 4 years with BPBI.

Abstract Medulloblastoma (MB), the most prevalent pediatric brain malignancy, exhibits a notable sex bias in incidence and survival rates. Males have a higher incidence rate across all age groups and have worse prognoses than their females for ages groups over three years old. There is growing evidence that the biological sex is a major variable driving differences in cancer incidence and treatment responses. However, the underlying mechanism is not well understood. Here, we report an unanticipated sex-biased role of the oncogene Yap1 in SHH medulloblastoma. To elucidate whether YAP1 is a cooperating oncogene for SMO-induced SHH MB formation, we genetically deleted Yap1 from a mouse model of SHH MB (Fsmo:GFAP-cre) and observed that Yap1 deletion significantly prolongs survival in males, but not females. Through an integrated multi-omics approach, we demonstrate that YAP1 is required to maintain cancer stem cells in both sexes. In contrast, Yap1 plays a more critical role in regulating genes that promote immune evasion in male MB cells than in female cells. Notably, YAP1 regulates the expression of the immune checkpoint molecule Cd276/B7-H3, which suppresses cytotoxic T cell function. CD276 blockade through a blocking antibody or Yap1 deletion in MB cells is sufficient to reverse T cell suppression in vitro, and Yap1 deletion is sufficient to significantly increase immune infiltrates and T cell activation in vivo. In females, neither CD276 blockade nor Yap1 deletion in MB cells is sufficient to reverse T cell suppression: it required combined inhibition of YAP1 and CD276. We also identified a new set of YAP1 target genes in vivo and these gene signatures predict survival in male but not patients across multiple human cancer types. These findings implicate our findings beyond medulloblastoma and indicate highly conserved dependencies to YAP1 in a sex-biased manner. In conclusion, Yap1 is a critical cooperating oncogene for SMO-induced MB and it promotes MB progression by promoting cancer stem cells and immune suppression.