This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the CTSA Program led by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) at the United States. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers.
View Article and Find Full Text PDFBackground: FOXF2, a member of the transcription factor FOX family proteins, plays a key role in tumorigenesis and tumor aggressiveness. However, the potential molecular mechanism of FOXF2 in esophageal squamous cell carcinoma (ESCC) remains largely unknown. Exploring its role and mechanism in ESCC progression may help identify new diagnostic markers and therapeutic targets.
View Article and Find Full Text PDFBackground: Cardiomyocyte oxidative stress significantly contributes to the progression of hypertension-induced heart failure, highlighting the need for targeted therapies. We developed a novel peptide, NPA7, that coactivates the GC-A (guanylyl cyclase A)/cGMP and MasR (Mas receptor)/cAMP pathway. This study aimed to test NPA7's ability to inhibit oxidative stress by modulating the p62-KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2-related factor 2) pathway in human cardiomyocytes (HCMs) and a rat model of hypertension.
View Article and Find Full Text PDFBackground: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.
Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.
Probing regional glycogen metabolism in humans non-invasively has been challenging due to a lack of sensitive approaches. Here we studied human muscle glycogen dynamics post-exercise with a spatial resolution of millimeters and temporal resolution of minutes, using relayed nuclear Overhauser effect (glycoNOE) MRI. Data at 5T showed a homogeneous distribution of glycogen in resting muscle, with an average concentration of 99 ± 13 mM.
View Article and Find Full Text PDFPurpose: To investigate the ability to quantify fundus curvature and detect posterior staphyloma using widefield optical coherence tomography (OCT).
Design: Cross-sectional diagnostic evaluation.
Methods: This study reviewed 205 highly myopic eyes of 205 participants.
Background: Liver hemangiomas (HGs) are characterized by cavernous venous spaces delineated by a lining of vascular endothelial cells and interspersed with connective tissue septa. Typically, a liver HG has higher apparent diffusion coefficient (ADC) and T2 values than those of hepatocellular carcinomas (HCCs) and liver metastases, and lower ADC and T2 values than those of liver simple cysts. However, a portion of HGs shows ADC and T2 overlapping with those of HCC, liver metastasis, and simple cyst.
View Article and Find Full Text PDFBackground: In STREAM-1 (Strategic Reperfusion Early After Myocardial Infarction), excess intracranial hemorrhage occurred in patients aged ≥75 years receiving full-dose tenecteplase as part of a pharmaco-invasive strategy, whereas no further intracranial hemorrhage occurred after halving the tenecteplase dose. In STREAM-2 (Second Strategic Reperfusion Early After Myocardial Infarction), half-dose tenecteplase was an effective and safe pharmaco-invasive strategy in older patients with ST-segment-elevation myocardial infarction presenting within <3 hours, compared with primary percutaneous coronary intervention (PCI). We prespecified evaluating the efficacy and safety of a half-dose versus full-dose pharmaco-invasive strategy and compared the half-dose pharmaco-invasive strategy to primary PCI in patients aged ≥75 years.
View Article and Find Full Text PDFBackground: Mitochondrial dysfunction is a key factor in the development of atherogenesis. METTL4 (methyltransferase-like protein 4) mediates N6- methyldeoxyadenosine (6mA) of mammalian mitochondrial DNA (mtDNA). However, the role of METTL4-mediated mitoepigenetic regulation in atherosclerosis is still unknown.
View Article and Find Full Text PDFDespite its limitations, restriction enzyme (RE)-mediated cleavage remains the prevalent method for generating sticky ends in DNA assembly. Here, we present RNase HII Fusion (RH2Fusion), a robust system for user-defined sticky ends, enabling scarless assembly of multiple DNA fragments alongside simultaneous site-directed mutagenesis (SDM) at multiple sites. In bacterial cells, DNA fragments with ribonucleotide modifications are expected to form complementary 3' overhangs after RNase HII treatment, followed by annealing and recombination via the bacterial self-repair system.
View Article and Find Full Text PDFOncolytic viruses have been considered promising cancer immunotherapies. However, oncovirotherapy agents impart durable responses in only a subset of cancer patients. Thus, exploring the cellular and molecular mechanisms underlying the heterogeneous responses in patients can provide guidance to develop more effective oncolytic virus therapies.
View Article and Find Full Text PDFRationale And Objectives: High-grade patterns, visceral pleural invasion, lymphovascular invasion, spread through air spaces, and lymph node metastasis are high-risk factors and associated with poor prognosis in lung adenocarcinomas (LUADs). This study aimed to construct and validate a radiomic model and a radiographic model derived from low-dose CT (LDCT) for predicting high-risk LUADs in solid and part-solid nodules.
Materials And Methods: This study retrospectively enrolled 658 pathologically confirmed LUADs from July 2018 to December 2022 from four centers, which were divided into training set (n=411), internal validation set (n=139), and external validation set (n=108).
Objectives: To develop and externally validate a fully automated diagnostic convolutional neural network (CNN) model for cirrhosis based on liver MRI and serum biomarkers.
Methods: This multicenter retrospective study included consecutive patients receiving pathological evaluation of liver fibrosis stage and contrast-enhanced liver MRI between March 2010 and January 2024. On the training dataset, an MRI-based CNN model was constructed for cirrhosis against pathology, and then a combined model was developed integrating the CNN model and serum biomarkers.
Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.
Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals.
Background: Circulating proteins in blood are involved in various physiological processes, but their contributions to blood pressure regulation remain partially understood. In traditional observational studies, identifying circulating proteins causally associated with blood pressure is challenging because of potentially unmeasured confounding and possible reverse causality.
Methods: Two-sample Mendelian randomization analyses were conducted to estimate the causal effects of 2270 circulating proteins (data sourced from 8 genome-wide association studies) on diastolic blood pressure, systolic blood pressure, and pulse pressure.
Development of large-scale alkaline seawater electrolysis requires robust and corrosion-resistant anodes. Here we propose engineering NiFe layered double hydroxide (LDH)-based anodes by incorporating a series of anions into the LDH interlayers. The most optimal NiFe LDH anode with intercalated phosphates demonstrates stable operation at a high current density of 1.
View Article and Find Full Text PDFRationale And Objectives: To explore the value of diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator (MAP) magnetic resonance imaging histogram analysis in evaluating the grade and proliferative activity of meningiomas.
Materials And Methods: A total of 134 meningioma patients were prospectively included and underwent magnetic resonance diffusion imaging. The whole-tumor histogram parameters were extracted from multiple functional maps.
Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer's disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here made advances by pinpointing a Lactobacillus murinus (L.m.
View Article and Find Full Text PDFThere exists a pressing need for a non-invasive panel that differentiates mild fibrosis from non-fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). In this work, we applied quantitative lipidomics and sterolomics on sera from the PERSONS cohort with biopsy-based histological assessment of liver pathology. We trained a lasso regression model using quantitative omics data and clinical variables, deriving a combinatorial panel of lipids and clinical indices that differentiates mild fibrosis (>F1, n = 324) from non-fibrosis (F0, n = 195), with an area under receiver operating characteristic curve (AUROC) at 0.
View Article and Find Full Text PDFAs an important nonoil route for acquiring aromatics, the highly efficient conversion of methanol to aromatics over Zn/ZSM-5 zeolites remains an ongoing challenge. In this work, we developed a uniform loading approach of zinc and further combined it with a hollow capsule structure to design the high-performance Zn/ZSM-5 catalyst. The electrostatic assembly among EDTA, -butylamine and negative silica-alumina gel gave rise to an "Inorganic-Organic Hybrid Sphere" in form of Na·{[(SiO)Al]/(SiO)(-butylamine)(EDTA)(-butylamine)(SiO), which further transformed into mesoporous aluminosilicates sphere (MASS) through calcination.
View Article and Find Full Text PDFHydrogel-based tissue expansion combined with mass spectrometry (MS) offers an emerging spatial proteomics approach. Here, we present a filter-aided expansion proteomics (FAXP) strategy for spatial proteomics analysis of archived formalin-fixed paraffin-embedded (FFPE) specimens. Compared to our previous ProteomEx method, FAXP employed a customized tip device to enhance both the stability and throughput of sample preparation, thus guaranteeing the reproducibility and robustness of the workflow.
View Article and Find Full Text PDFRationale And Objectives: Accurate prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is crucial for guiding treatment. This study evaluates and compares the performance of clinicoradiologic, traditional radiomics, deep-learning radiomics, feature fusion, and decision fusion models based on multi-region MR habitat imaging using six machine-learning classifiers.
Materials And Methods: We retrospectively included 300 HCC patients.
Crucial for cell activities, ion channels are key drug discovery targets. Although small-molecule and peptide modulators dominate ion channel drug discovery, antibodies are emerging as an alternative modality. However, challenges persist in generating potent antibodies, especially for channels with limited extracellular epitopes.
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