Imprinting abnormalities pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, with no universal correction method owing to their complexity and stochastic nature. In this study, we targeted these defects at their source-embryos from same-sex parents-aiming to establish a stable, maintainable imprinting pattern de novo in mammalian cells. Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate.
View Article and Find Full Text PDFPurpose To develop and evaluate a deep learning-based prognostic model for predicting survival in locoregionally- advanced nasopharyngeal carcinoma (LA-NPC) using serial MRI before and after induction chemotherapy (IC). Materials and Methods This multicenter retrospective study included 1039 LA-NPC patients (779 male, 260 female, mean age 44 [standard deviation: 11]) diagnosed between April 2009 and December 2015. A radiomics- clinical prognostic model (Model RC) was developed using pre-and post-IC MRI and other clinical factors using graph convolutional neural networks (GCN).
View Article and Find Full Text PDFRationale And Objectives: To propose a novel MRI-based hyper-fused radiomic approach to predict pathologic complete response (pCR) to neoadjuvant therapy (NAT) in breast cancer (BC).
Materials And Methods: Pretreatment dynamic contrast-enhanced (DCE) MRI and ultra-multi-b-value (UMB) diffusion-weighted imaging (DWI) data were acquired in BC patients who received NAT followed by surgery at two centers. Hyper-fused radiomic features (RFs) and conventional RFs were extracted from DCE-MRI or UMB-DWI.
Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.
Methods: Patients with ischemic stroke presenting 4.
DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2.
View Article and Find Full Text PDFBackground: Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile.
Methods: This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022.
Background: Type A aortic dissection (TAAD) is a life-threatening condition characterized by complex pathophysiology, in which macrophages play a critical but not yet fully understood role. This study focused on the role of endothelial cells with elevated expression of ACKR1 (atypical chemokine receptor 1) and their interaction with proinflammatory macrophages in TAAD development.
Methods: Single-cell transcriptomic analysis of human aortic tissues was used to identify cellular heterogeneity in TAAD.
Rationale And Objectives: To construct and validate a clinical-radiomics model based on radiomics features extracted from two-stage multimodal ultrasound and clinicopathologic information for early predicting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients treated with NAC.
Materials And Methods: Consecutive women with biopsy-proven breast cancer undergoing multimodal US pretreatment and after two cycles of NAC and followed by surgery between January 2014 and November 2023 were retrospectively collected for clinical-radiomics model construction (n = 274) and retrospective test (n = 134). The predictive performance of it was further tested in a subsequent prospective internal test set recruited between January 2024 to July 2024 (n = 76).
Background Gallium 68 (Ga) pentixafor has emerged as a potential C-X-C chemokine receptor type 4 (CXCR4)-targeted radiotracer for neuroendocrine tumor, yet its application in Cushing disease remains uncertain. Purpose To assess the diagnostic accuracy and value of Ga-pentixafor PET/MRI in localizing adrenocorticotropic hormone (ACTH)-secreting pituitary tumors in Cushing disease. Materials and Methods A prospective single-center study was conducted from March 2023 to February 2024 in participants with Cushing disease scheduled for surgical pituitary tumor resection.
View Article and Find Full Text PDFBackground: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().
Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.
Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.
Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.
Phytophthora pathogens secrete numerous apoplastic effectors to manipulate host immunity. Herein, we identified a polysaccharide lyase 1 protein, PsPL1, which acts as an essential virulence factor of P. sojae infection in soybean.
View Article and Find Full Text PDFIn deep-space optical communication systems, precise pointing and aiming of the laser beam is essential to ensure the stability of the laser link. In this paper, an adaptive compound control system based on adaptive feedforward and Proportional-Integral-Differentiation (PID) feedback is proposed. The feedforward controller is stabilized using Youla-Kucera (YK) parameterization.
View Article and Find Full Text PDFBackground: We aim to assess the efficacy of rapid local ischemic postconditioning (RL-IPostC) following successful reperfusion in patients with acute ischemic stroke with anterior circulation large vessel occlusion who underwent endovascular thrombectomy.
Methods: We conducted an ambidirectional cohort study with 78 prospectively enrolled patients with RL-IPostC and endovascular thrombectomy and 129 retrospectively enrolled patients with endovascular thrombectomy. The RL-IPostC procedure involved 5 cycles of 15-s balloon inflation and deflation in the ipsilateral internal carotid artery.
Two-dimensional (2D) ion crystals may represent a promising path to scale up qubit numbers for ion trap quantum information processing. However, to realize universal quantum computing in this system, individually addressed high-fidelity two-qubit entangling gates still remain challenging due to the inevitable micromotion of ions in a 2D crystal as well as the technical difficulty in 2D addressing. Here we demonstrate two-qubit entangling gates between any ion pairs in a 2D crystal of four ions.
View Article and Find Full Text PDFGlucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM.
View Article and Find Full Text PDFBackground: Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery.
View Article and Find Full Text PDF