Given that optical thermometers are widely used due to their unique advantages, this study aims to address critical challenges in existing technologies, such as insufficient sensitivity, limited temperature measurement ranges, and poor signal recognition capabilities. Herein, we develop a thermometer based on the fluorescence intensity ratio (FIR) of Sb-doped CsNaInCl (CsNaInCl:Sb). As the temperature increases from 203 to 323 K, the thermally induced transition from triplet to singlet self-trapped excitons (STEs) leads to enhanced 455 nm photoluminescence (PL) from singlet STE recombination.
View Article and Find Full Text PDFMosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.
View Article and Find Full Text PDFMembers of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.
View Article and Find Full Text PDFBackground: Postdischarge contacts (PDCs) after hospitalization are common practice, but their effectiveness in reducing use of acute care after discharge remains unclear.
Purpose: To assess the effects of PDC on 30-day emergency department (ED) visits, 30-day hospital readmissions, and patient satisfaction.
Data Sources: MEDLINE, Embase, and CINAHL searched from 2012 to 25 May 2023.
Interleukin 1 beta (IL-1β) and IL-1 receptor antagonist (IL-1RA) are both upregulated following traumatic injury. As IL-1RA blocks inflammatory signaling by IL-1β, overexpression of IL-1β relative to IL-1RA may drive inflammatory diseases. As such, determination of the relationship between IL-1β to IL-1RA expression levels in horses may provide insight into disease states or serve as a therapeutic readout of response to medical interventions.
View Article and Find Full Text PDFProteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that target undruggable proteins, enhance selectivity and prevent target accumulation through catalytic activity. The unique structure of PROTACs presents challenges in structural identification and drug design. Liquid chromatography (LC), combined with mass spectrometry (MS), enhances compound annotation by providing essential retention time (RT) data, especially when MS alone is insufficient.
View Article and Find Full Text PDFLarge language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a 'passing' score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval.
View Article and Find Full Text PDFNew treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.
View Article and Find Full Text PDFThe GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are devastating neurodegenerative disorders caused by β-hexosaminidase A (HexA) deficiency. In the Sandhoff disease mouse model, rescue potential was severely reduced when HexA was introduced after disease onset. Here, we assess the effect of recombinant HexA and HexD3, a newly engineered mimetic of HexA optimized for the treatment of Tay-Sachs disease and Sandhoff disease.
View Article and Find Full Text PDFAn outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 pandemic, has resulted in over 7 million confirmed deaths. In addition to severe respiratory and systematic symptoms, several comorbidities increase the risk of fatal outcomes. Therefore, it is essential to investigate the impact of COVID-19 on pre-existing conditions in patients, such as cancer and other infectious diseases.
View Article and Find Full Text PDFRET (Rearranged during transfection) kinase is a validated target for non-small cell lung cancer (NSCLC). In 2020, two selective RET inhibitors, selpercatinib and pralsetinib were approved by the US FDA. However, high treatment costs and clinically acquired resistance (e.
View Article and Find Full Text PDFPurpose: Cumulative cisplatin doses of ≥ 200 mg/m improve survival in adults with head-and-neck squamous cell carcinoma (HNSCC) undergoing chemoradiation, but many older adults with HNSCC cannot receive this prognostically relevant dose due to toxicities. This study aims to develop predictive models to assess the likelihood of older adults with HNSCC receiving ≥ 200 mg/m cisplatin during chemoradiation.
Methods: 366 patients from the SENIOR database, an international cohort of adults ≥ 65 years with HNSCC, received definitive chemoradiation with single-agent cisplatin and were analyzed.
Intraductal papillary mucinous neoplasms (IPMN) are commonly detected pancreatic cysts that may transform into pancreatic ductal adenocarcinoma (PDAC). Predicting which IPMNs will progress to PDAC remains a clinical challenge. Moreover, identifying those clinically evident IPMNs for which a surveillance approach is best is a dire clinical need.
View Article and Find Full Text PDFBehav Res Methods
December 2024
The assessment of color vision is crucial in both fundamental visual research and clinical diagnosis. However, existing tools for color vision assessment are limited by various factors. This study introduces a novel, efficient method for color vision assessment, which is based on a continuous motion tracking task and a Kalman filter model.
View Article and Find Full Text PDFProtein-ligand binding affinity prediction is a crucial and challenging task in the field of drug discovery. However, traditional simulation-based computational approaches are often prohibitively time-consuming, limiting their practical utility. In this study, we introduce a novel deep learning method, CPIScore, which leverages the capabilities of Transformer and Graph Convolutional Networks (GCN) to enhance the prediction of protein-ligand binding affinity.
View Article and Find Full Text PDFThe continuous impact of COVID-19 on aquatic environments has attracted considerable attention, primarily focusing on short-term water quality effects during lockdown, while studies on changes following the lifting of restrictions are relatively limited. Following adjustments to China's pandemic public policy in December 2022, the effects on water quality and nutrient status in lakes and reservoirs remain unclear. In this study, we collected national environmental monitoring data comprising 15 indicators of water quality, meteorology, soil, and economic factors, from 86 lakes and reservoirs across China between March 2021 and December 2023.
View Article and Find Full Text PDFAboveground biomass (AGB) is a critical indicator for monitoring the crop growth status and predicting yields. UAV remote sensing technology offers an efficient and non-destructive method for collecting crop information in small-scale agricultural fields. High-resolution hyperspectral images provide abundant spectral-textural information, but whether they can enhance the accuracy of crop biomass estimations remains subject to further investigation.
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