Understanding transcriptional heterogeneity in cancer cells and its implication for treatment response is critical to identify how resistance occurs and may be targeted. Such heterogeneity can be captured by in vitro studies through clonal barcoding methods. We present TraCSED (Transformer-based modeling of Clonal Selection and Expression Dynamics), a dynamic deep learning approach for modeling clonal selection.
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: 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.
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 PDFProc Natl Acad Sci U S A
October 2024
This study aims to determine the impact of adjunct nondamaging focal laser therapy on the number of anti-vascular endothelial growth factor (anti-VEGF) injections and visual acuity (VA) and imaging in patients with diabetic macular edema (DME). A retrospective analysis of 18 eyes of 14 patients with DME treated with a single session of the PASCAL 532 nm Synthesis Photocoagulator with Endpoint Management was conducted. Demographic data, VA, imaging, laser parameters, and anti-VEGF injection burden six months before and after treatment were collected.
View Article and Find Full Text PDFAlthough high-dimensional clinical data (HDCD) are increasingly available in biobank-scale datasets, their use for genetic discovery remains challenging. Here we introduce an unsupervised deep learning model, Representation Learning for Genetic Discovery on Low-Dimensional Embeddings (REGLE), for discovering associations between genetic variants and HDCD. REGLE leverages variational autoencoders to compute nonlinear disentangled embeddings of HDCD, which become the inputs to genome-wide association studies (GWAS).
View Article and Find Full Text PDFThe nitration reaction of aromatic compounds is one of the extensively studied chemical reactions that result in the manufacturing of various industrial products applied in pharmaceuticals, dyes, perfumes, and explosives. A series of modified sulfated zirconia (SZ) catalysts SO/ZrO-MO (M=Ce, Co, Mn, Zn, and M/SZ) doped with different metal elements by a coprecipitation method were investigated in the toluene nitration reaction. Various characterization techniques (X-ray diffraction, Brunauer-Emmett-Teller, thermogravimetric analysis, X-ray photoelectron spectroscopy, and temperature-programmed desorption of ammonia) indicated that doping metal elements in SZ led to excellent catalytic properties, increasing the specific surface area of the catalyst and facilitating the formation of a stable tetragonal zirconia phase.
View Article and Find Full Text PDFT cell receptor (TCR)-engineered T cell therapy is a promising potential treatment for solid tumors, with preliminary efficacy demonstrated in clinical trials. However, obtaining clinically effective TCR molecules remains a major challenge. We have developed a strategy for cloning tumor-specific TCRs from long-term surviving patients who have responded to immunotherapy.
View Article and Find Full Text PDFThe reactivity of the rare earth metal alkyl complexes RE(CHSiMe)(THF) () [RE = Y (), Yb (), Lu (); = 2,5-[(2-pyrrolyl)CPh](-methylpyrrole)] with various nitriles and isonitriles has been fully developed. Treatment of the yttrium monoalkyl complex () with 2 equiv of aromatic nitriles afforded the symmetric trisubstituted β-diketiminato yttrium complexes (, , and through successive cyano group insertion into the RE-C bond and 1,3-H shift or the unsymmetric trisubstituted β-diketiminato yttrium complex () unexpectedly via a 1,3-SiMe shift when 4-(trifluoromethyl)benzonitrile was used in this reaction under the same conditions. By treating with 2 equiv of tolyl acetonitrile, an activation of the C-H bond occurred to form the corresponding β-aryl keteniminato complexes and .
View Article and Find Full Text PDFBackground: Calcification of the aortic valve leads to increased leaflet stiffness and consequently results in the development of calcific aortic valve disease (CAVD). However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified a novel aortic valve calcification-associated PIWI-interacting RNA (piRNA; AVCAPIR) that increases valvular calcification and promotes CAVD progression.
View Article and Find Full Text PDFGenerating ion-photon entanglement is a crucial step for scalable trapped-ion quantum networks. To avoid the crosstalk on memory qubits carrying quantum information, it is common to use a different ion species for ion-photon entanglement generation such that the scattered photons are far off-resonant for the memory qubits. However, such a dual-species scheme can be subject to inefficient sympathetic cooling due to the mass mismatch of the ions.
View Article and Find Full Text PDFObjectives: To investigate the clinical application of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in the etiological diagnosis and treatment of refractory pneumonia (RTP) in children.
Methods: A retrospective analysis was performed on 160 children with RTP who were admitted to the Department of Pediatric Internal Medicine, Maternal and Child Health Hospital of Inner Mongolia Autonomous Region, from January 2020 to March 2023. According to whether mNGS was performed, they were divided into two groups: mNGS (=80) and traditional testing (=80).
A central question in neural tissue engineering is how the tissue-engineered nerve (TEN) translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes. Here, we report a skin-derived precursor-induced Schwann cell (SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft (SKP-SCs-TEN) that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral, histological, and electrophysiological evidence. For achieving better effect of neuroregeneration, this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix (ECM).
View Article and Find Full Text PDFBackground Preoperative assessment of follicular thyroid neoplasms is challenging using the current US risk stratification systems (RSSs) that are applicable to papillary thyroid neoplasms. Purpose To develop a US feature-based RSS for differentiating between follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC) in biopsy-proven follicular neoplasm and compare it with existing RSSs. Materials and Methods This retrospective multicenter study included consecutive adult patients who underwent conventional US and received a final diagnosis of follicular thyroid neoplasm from seven centers between January 2018 and December 2022.
View Article and Find Full Text PDFEpstein-Barr virus (EBV) is a type of human -herpesvirus, and its reactivation plays an important role in the development of EBV-driven Burkitt lymphoma (BL). Despite intensive chemotherapy, the prognosis of relapsed/refractory BL patients remains unfavorable, and a definitive method to completely eliminate latent EBV infection is lacking. Previous studies have demonstrated that histone deacetylase (HDAC) inhibitors can induce the transition of EBV from latency to the lytic phase.
View Article and Find Full Text PDFNi-rich layered ternary cathodes (i.e., LiNiCoMO, M = Mn or Al, + + = 1 and ≥ 0.
View Article and Find Full Text PDFA robust in vitro model of the human respiratory epithelium, including the alveolar and the airway epithelium, is essential for understanding the biology and pathology of the human respiratory system. We previously described a protocol to derive human lung organoids from primary lung tissues. We now describe a protocol to induce bidirectional differentiation to generate mature alveolar or airway organoids.
View Article and Find Full Text PDFRelapsed or refractory (r/r) mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a poor prognosis. Bruton tyrosine kinase (BTK) is a mediator of B-cell receptor signaling and is associated with the development of B-cell lymphomas. Patients with r/r MCL were enrolled in this phase 1/2 study and treated with orelabrutinib, a novel, highly selective BTK inhibitor.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2023
Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles).
View Article and Find Full Text PDF