PTPRO-related CD8⁺ T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer

Background: Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in “immune-cold” breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers. Methods: ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8+ T-cell signatures (PTSs). The Kaplan–Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets. Results: High PTPRO expression was related to high infiltration levels of CD8+ T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8+ T cells in the TIME, we focused on the impact of PTPRO expression on CD8+ T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs). Conclusion: PTPRO significantly impacts CD8+ T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients

Large-area epitaxial growth of curvature-stabilized ABC trilayer graphene.

The properties of van der Waals (vdW) materials often vary dramatically with the atomic stacking order between layers, but this order can be difficult to control. Trilayer graphene (TLG) stacks in either a semimetallic ABA or a semiconducting ABC configuration with a gate-tunable band gap, but the latter has only been produced by exfoliation. Here we present a chemical vapor deposition approach to TLG growth that yields greatly enhanced fraction and size of ABC domains. The key insight is that substrate curvature can stabilize ABC domains. Controllable ABC yields ~59% were achieved by tailoring substrate curvature levels. ABC fractions remained high after transfer to device substrates, as confirmed by transport measurements revealing the expected tunable ABC band gap. Substrate topography engineering provides a path to large-scale synthesis of epitaxial ABC-TLG and other vdW materials

Searching Collaborative Agents for Multi-plane Localization in 3D Ultrasound

3D ultrasound (US) is widely used due to its rich diagnostic information, portability and low cost. Automated standard plane (SP) localization in US volume not only improves efficiency and reduces user-dependence, but also boosts 3D US interpretation. In this study, we propose a novel Multi-Agent Reinforcement Learning (MARL) framework to localize multiple uterine SPs in 3D US simultaneously. Our contribution is two-fold. First, we equip the MARL with a one-shot neural architecture search (NAS) module to obtain the optimal agent for each plane. Specifically, Gradient-based search using Differentiable Architecture Sampler (GDAS) is employed to accelerate and stabilize the training process. Second, we propose a novel collaborative strategy to strengthen agents' communication. Our strategy uses recurrent neural network (RNN) to learn the spatial relationship among SPs effectively. Extensively validated on a large dataset, our approach achieves the accuracy of 7.05 degree/2.21mm, 8.62 degree/2.36mm and 5.93 degree/0.89mm for the mid-sagittal, transverse and coronal plane localization, respectively. The proposed MARL framework can significantly increase the plane localization accuracy and reduce the computational cost and model size.Comment: Early accepted by MICCAI 202

FetusMapV2: Enhanced Fetal Pose Estimation in 3D Ultrasound

Fetal pose estimation in 3D ultrasound (US) involves identifying a set of associated fetal anatomical landmarks. Its primary objective is to provide comprehensive information about the fetus through landmark connections, thus benefiting various critical applications, such as biometric measurements, plane localization, and fetal movement monitoring. However, accurately estimating the 3D fetal pose in US volume has several challenges, including poor image quality, limited GPU memory for tackling high dimensional data, symmetrical or ambiguous anatomical structures, and considerable variations in fetal poses. In this study, we propose a novel 3D fetal pose estimation framework (called FetusMapV2) to overcome the above challenges. Our contribution is three-fold. First, we propose a heuristic scheme that explores the complementary network structure-unconstrained and activation-unreserved GPU memory management approaches, which can enlarge the input image resolution for better results under limited GPU memory. Second, we design a novel Pair Loss to mitigate confusion caused by symmetrical and similar anatomical structures. It separates the hidden classification task from the landmark localization task and thus progressively eases model learning. Last, we propose a shape priors-based self-supervised learning by selecting the relatively stable landmarks to refine the pose online. Extensive experiments and diverse applications on a large-scale fetal US dataset including 1000 volumes with 22 landmarks per volume demonstrate that our method outperforms other strong competitors.Comment: 16 pages, 11 figures, accepted by Medical Image Analysis(2023

Quantitative real-time RT-PCR validation of differential mRNA expression of SPARC, FADD, Fascin, COL7A1, CK4, TGM3, ECM1, PPL and EVPL in esophageal squamous cell carcinoma

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors and typically presents at an advanced and rapidly fatal stage. To better understand the role of genetics in the etiology and prevention of ESCC and to identify potential susceptibility genes as well as early detection markers, we previously compared tumor and matched normal tissues from ESCC patients from a high-risk area of China using cDNA expression microarrays and identified 41 differentially-expressed genes (13 over-expressed and 28 under-expressed). METHODS: In the current study, we validated and quantitated differential mRNA expression in a sample of nine of these 41 genes, including four that were over-expressed (SPARC, FADD, Fascin, COL7A1), and five that were under-expressed (CK4, TGM3, ECM1, PPL, EVPL), in 75 new ESCC patients using quantitative Real-time RT-PCR and the 2(-ΔΔCT )method to examine both tumor and matched normal tissue. In addition, we examined expression patterns for these genes by selected demographic and clinical characteristics. RESULTS: Four previously over-expressed (tumor ≥2-fold normal) genes were all increased in the majority of new ESCC patients: SPARC was increased in 71% of patients, Fascin in 70%, FADD in 63%, and COL7A1 in 57%. Five previously under-expressed (tumor ≤0.5-fold normal) genes similarly showed decreased mRNA expression in two-thirds or more of patients: CK4 was decreased in 83% of patients, TGM3 in 77%, ECM1 in 73%, and PPL and EVPL in 67% each. In subset analyses, associations with age (for COL7A1), family history (for PPL and ECM1), and alcohol use (for SPARC and Fascin) were also noted. CONCLUSION: These data indicate that these nine genes have consistent differential mRNA expression, validating results of our previous cDNA array results, and affirming their potential role in the early detection of ESCC

Magnetic Properties of Single Transition-Metal Atom Absorbed Graphdiyne and Graphyne Sheet

The electronic and magnetic properties of single 3d transition-metal(TM) atom (V, Cr, Mn, Fe, Co, and Ni) adsorbed graphdiyne (GDY) and graphyne (GY) are systematically studied using first-principles calculations within the density functional framework. We find that the adsorption of TM atom not only efficiently modulates the electronic structures of GDY/GY system, but also introduces excellent magnetic properties, such as half-metal and spin-select half-semiconductor. Such modulation originates from the charge transfer between TM adatom and the GDY/GY sheet as well as the electron redistribution of the TM intra-atomic s, p, and d orbitals. Our results indicate that the TM adsorbed GDY/GY are excellent candidates for spintronics.Comment: 8 pages, 7 figure

Short dual antiplatelet therapy in patients with high bleeding risk undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

Background The efficacy and safety of an abbreviated duration of dual antiplatelet therapy (DAPT) in patients with high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) (PCI-HBR patients) remain controversial. Methods The Cochrane Library, PubMed, EMBASE, and Ovid MEDLINE databases were searched. Studies that enrolled PCI-HBR patients as research subjects, compared different DAPT durations, and reported incidences of major adverse cardiac events (MACE) and net adverse clinical events (NACE) in PCI-HBR patients were obtained. The studies were stratified according to the DAPT duration (1, 3, and 6 months), and meta-analysis was subsequently performed. Results Nine studies (10 cohorts) were included in the meta-analysis. Compared with those who received DAPT for >1 month, PCI-HBR patients who received the 1-month DAPT regimen had comparable risks of NACE and MACE. Compared to those who received DAPT for >3 months, the risk of developing MACE in PCI-HBR patients who received the 3-month DAPT was not increased; however, the risk of ischemic stroke and stent thrombosis increased. Compared to those who received DAPT for >6 months, patients who received the 6-month DAPT had a reduction in the risk of major bleeding without an increase in NACE and MACE. Conclusions Shortening the DAPT regimen to 1 or 6 months did not increase the risk of MACE, and the 6-month DAPT regimen reduced the risk of major bleeding. However, the 3-month DAPT regimen increased the risk of ischemic stroke. Thus, shortened DAPT reduced the risk of MACE and bleeding, with a small absolute increase in ischemic strokes