Deconvolution of Human Urine across the Transcriptome and Metabolome.

BACKGROUND: Early detection of the cell type changes underlying several genitourinary tract diseases largely remains an unmet clinical need, where existing assays, if available, lack the cellular resolution afforded by an invasive biopsy. While messenger RNA in urine could reflect the dynamic signal that facilitates early detection, current measurements primarily detect single genes and thus do not reflect the entire transcriptome and the underlying contributions of cell type-specific RNA. METHODS: We isolated and sequenced the cell-free RNA (cfRNA) and sediment RNA from human urine samples (n = 6 healthy controls and n = 12 kidney stone patients) and measured the urine metabolome. We analyzed the resulting urine transcriptomes by deconvolving the noninvasively measurable cell type contributions and comparing to plasma cfRNA and the measured urine metabolome. RESULTS: Urine transcriptome cell type deconvolution primarily yielded relative fractional contributions from genitourinary tract cell types in addition to cell types from high-turnover solid tissues beyond the genitourinary tract. Comparison to plasma cfRNA yielded enrichment of metabolic pathways and a distinct cell type spectrum. Integration of urine transcriptomic and metabolomic measurements yielded enrichment for metabolic pathways involved in amino acid metabolism and overlapped with metabolic subsystems associated with proximal tubule function. CONCLUSIONS: Noninvasive whole transcriptome measurements of human urine cfRNA and sediment RNA reflects signal from hard-to-biopsy tissues exhibiting low representation in blood plasma cfRNA liquid biopsy at cell type resolution and are enriched in signal from metabolic pathways measurable in the urine metabolome.

A high-spin s-triazine linked fluorenyl radical polymer.

The syntheses of high-spin organic polymers have been a daunting task due to the highly reactive nature of organic radicals, especially when they are ferromagnetically coupled. In this paper, we report our approach to obtain high-spin organic polymers, in which a reasonably stable fluorenyl radical was employed as the primary radical unit, and s-triazine serves as the connector that facilitates ferromagnetic coupling between them. Initially, the diamagnetic polymer precursor was synthesized by cyclotrimerization of a cyano-monomer. Subsequently, the high-spin polymers were obtained by oxidizing corresponding anionic polymers using O2 (6) or I2 (7). The temperature-dependent magnetic moments, and field-dependent magnetization data obtained from SQUID measurements revealed ferromagnetic couplings between primary radical units, with coupling J = 7.5 cm-1 and 38.6 cm-1. The percentages of primary unit in the radical form are 29%, and 47% for 6 and 7, respectively. Notably, this marks the first reported instance of a high-spin fluorenyl radical polymer exhibiting ferromagnetic coupling.

Electronic Documentation of Intraoperative Observation of Cystoscopic Procedures Using the cMDX Information System.

PURPOSE: Accurate documentation of lesions during transurethral resection of bladder tumors (TURBT) is essential for precise diagnosis, treatment planning, and follow-up care. However, optimizing schematic documentation techniques for bladder lesions has received limited attention. MATERIALS AND METHODS: This prospective observational study used a cMDX-based documentation system that facilitates graphical representation, a lesion-specific questionnaire, and heatmap analysis with a posterization effect. We designed a graphical scheme for bladder covering bladder landmarks to visualize anatomic features and to document the lesion location. The lesion-specific questionnaire was integrated for comprehensive lesion characterization. Finally, spatial analyses were applied to investigate the anatomic distribution patterns of bladder lesions. RESULTS: A total of 97 TURBT cases conducted between 2021 and 2023 were included, identifying 176 lesions. The lesions were distributed in different bladder areas with varying frequencies. The distribution pattern, sorted by frequency, was observed in the following areas: posterior, trigone, lateral right and anterior, and lateral left and dome. Suspicious levels were assigned to the lesions, mostly categorized either as indeterminate or moderate. Lesion size analysis revealed that most lesions fell between 5 and 29 mm. CONCLUSION: The study highlights the potential of schematic documentation techniques for informed decision making, quality assessment, primary research, and secondary data utilization of intraoperative data in the context of TURBT. Integrating cMDX and heatmap analysis provides valuable insights into lesion distribution and characteristics.

Multiomics characterization of cell type repertoires for urine liquid biopsies.

Urine is assayed alongside blood in medicine, yet current clinical diagnostic tests utilize only a small fraction of its total biomolecular repertoire, potentially foregoing high-resolution insights into human health and disease. In this work, we characterized the joint landscapes of transcriptomic and metabolomic signals in human urine. We also compared the urine transcriptome to plasma cell-free RNA, identifying a distinct cell type repertoire and enrichment for metabolic signal. Untargeted metabolomic measurements identified a complementary set of pathways to the transcriptomic analysis. Our findings suggest that urine is a promising biofluid yielding prognostic and detailed insights for hard-to-biopsy tissues with low representation in the blood, offering promise for a new generation of liquid biopsies.

Efficient Augmented Intelligence Framework for Bladder Lesion Detection.

PURPOSE: Development of intelligence systems for bladder lesion detection is cost intensive. An efficient strategy to develop such intelligence solutions is needed. MATERIALS AND METHODS: We used four deep learning models (ConvNeXt, PlexusNet, MobileNet, and SwinTransformer) covering a variety of model complexity and efficacy. We trained these models on a previously published educational cystoscopy atlas (n = 312 images) to estimate the ratio between normal and cancer scores and externally validated on cystoscopy videos from 68 cases, with region of interest (ROI) pathologically confirmed to be benign and cancerous bladder lesions (ie, ROI). The performance measurement included specificity and sensitivity at frame level, frame sequence (block) level, and ROI level for each case. RESULTS: Specificity was comparable between four models at frame (range, 30.0%-44.8%) and block levels (56%-67%). Although sensitivity at the frame level (range, 81.4%-88.1%) differed between the models, sensitivity at the block level (100%) and ROI level (100%) was comparable between these models. MobileNet and PlexusNet were computationally more efficient for real-time ROI detection than ConvNeXt and SwinTransformer. CONCLUSION: Educational cystoscopy atlas and efficient models facilitate the development of real-time intelligence system for bladder lesion detection.

A Novel Residual Frequency Estimation Method for GNSS Receivers.

In Global Navigation Satellite System (GNSS) receivers, residual frequency estimation methods are traditionally applied in the synchronization block to reduce the transient time from acquisition to tracking, or they are used within the frequency estimator to improve its accuracy in open-loop architectures. There are several disadvantages in the current estimation methods, including sensitivity to noise and wide search space size. This paper proposes a new residual frequency estimation method depending on differential processing. Although the complexity of the proposed method is higher than the one of traditional methods, it can lead to more accurate estimates, without increasing the size of the search space.