An integrated single-cell and spatial transcriptomic atlas of thyroid cancer progression identifies prognostic fibroblast subpopulations.

Thyroid cancer progression from curable well-differentiated thyroid carcinoma to highly lethal anaplastic thyroid carcinoma is distinguished by tumor cell de-differentiation and recruitment of a robust stromal infiltrate. Combining an integrated thyroid cancer single-cell sequencing atlas with spatial transcriptomics and bulk RNA-sequencing, we define stromal cell subpopulations and tumor-stromal cross-talk occurring across the histologic and mutational spectrum of thyroid cancer. We identify distinct inflammatory and myofibroblastic cancer-associated fibroblast (iCAF and myCAF) populations and perivascular-like populations.

Tenascin-C potentiates Wnt signaling in thyroid cancer.

Tenascin-C (TNC) is a secreted extracellular matrix protein that is highly expressed during embryonic development and re-expressed during wound healing, inflammation, and neoplasia. Studies in developmental models suggest that TNC may regulate the Wnt signaling pathway. Our lab has shown high levels of Wnt signaling and TNC expression in anaplastic thyroid cancer (ATC), a highly lethal cancer with an abysmal ~3-5 month median survival.

No Increased Risk of Major Adverse Cardiovascular Events following Nicotinamide Exposure.

Importance: Nicotinamide metabolites have recently been implicated in increased risk of major cardiovascular events (MACE). Supportive data about clinical risk of MACE for nicotinamide users is lacking.

Objective: To determine whether nicotinamide use results in an increase of MACE.

EVPsort: An Atlas of Small ncRNA Profiling and Sorting in Extracellular Vesicles and Particles.

Extracellular vesicles and particles (EVPs) play a crucial role in mediating cell-to-cell communication by transporting various molecular cargos, with small non-coding RNAs (ncRNAs) holding particular significance. A thorough investigation into the abundance and sorting mechanisms of ncRNA within EVPs is imperative for advancing their clinical applications. We have developed EVPsort, which not only provides an extensive overview of ncRNA profiling in 3,162 samples across various biofluids, cell lines, and disease contexts but also seamlessly integrates 19 external databases and tools.

FindAdapt: A python package for fast and accurate adapter detection in small RNA sequencing.

Adapter trimming is an essential step for analyzing small RNA sequencing data, where reads are generally longer than target RNAs ranging from 18 to 30 bp. Most adapter trimming tools require adapter information as input. However, adapter information is hard to access, specified incorrectly, or not provided with publicly available datasets, hampering their reproducibility and reusability.

Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk.

Importance: Clinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones.

Objective: To identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones.

Design, Setting, And Participants: This genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics.

scDemultiplex: An iterative beta-binomial model-based method for accurate demultiplexing with hashtag oligos.

Single-cell sequencing have been widely used to characterize cellular heterogeneity. Sample multiplexing where multiple samples are pooled together for single-cell experiments, attracts wide attention due to its benefits of increasing capacity, reducing costs, and minimizing batch effects. To analyze multiplexed data, the first crucial step is to demultiplex, the process of assigning cells to individual samples.

Phenome-Wide Association Study of Gene Variants and Differential Associations With Clinical Outcomes Across Populations in the Million Veteran Program a Multiethnic Biobank.

Introduction: Common variants in the gene are considered an evolutionary adaptation against urinary tract infections (UTIs) and have been implicated in kidney stone formation, chronic kidney disease (CKD), and hypertension. However, differences in variant-phenotype associations across population groups are unclear.

Methods: We tested associations between variants and up to 1528 clinical diagnosis codes mapped to phenotype groups in the Million Veteran Program (MVP), using published phenome-wide association study (PheWAS) methodology.

Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19.

Remdesivir is the first US Food and Drug Administration (FDA)-approved drug for the treatment of coronavirus disease 2019 (COVID-19). We conducted a retrospective pharmacogenetic study to examine remdesivir-associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID-19 between March 15, 2020, and June 30, 2021. Pharmacogene phenotypes were assigned using Stargazer.

APOL1 Risk Variants, Acute Kidney Injury, and Death in Participants With African Ancestry Hospitalized With COVID-19 From the Million Veteran Program.

Importance: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates.

Objective: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) variants G1 or G2 (high-risk group) have significantly increased rates of kidney disease.

A domain damage index to prioritizing the pathogenicity of missense variants.

Prioritizing causal variants is one major challenge for the clinical application of sequencing data. Prompted by the observation that 74.3% of missense pathogenic variants locate in protein domains, we developed an approach named domain damage index (DDI).

Beyond Programmed Death-Ligand 1: B7-H6 Emerges as a Potential Immunotherapy Target in SCLC.

Introduction: The programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors, atezolizumab and durvalumab, have received regulatory approval for the first-line treatment of patients with extensive-stage SCLC. Nevertheless, when used in combination with platinum-based chemotherapy, these PD-L1 inhibitors only improve overall survival by 2 to 3 months. This may be due to the observation that less than 20% of SCLC tumors express PD-L1 at greater than 1%.

A SAC Phosphoinositide Phosphatase Controls Rice Development via Hydrolyzing PI4P and PI(4,5)P.

Phosphoinositides (PIs) as regulatory membrane lipids play essential roles in multiple cellular processes. Although the exact molecular targets of PI-dependent modulation remain largely elusive, the effects of disturbed PI metabolism could be employed to identify regulatory modules associated with particular downstream targets of PIs. Here, we identified the role of (), which encodes a suppressor of actin (SAC) domain-containing phosphatase with unknown function in rice ().

Synthesis of surface molecularly imprinted nanoparticles for recognition of lysozyme using a metal coordination monomer.

Molecularly imprinted polymers against proteins are regarded as promising substitutes for natural antibodies, but have been frustrated with the problems including reduced interaction between functional monomers and protein template in the aqueous media required during their synthesis and restricted mass transfer across the resulting crosslinked polymer matrixes. For addressing these issues, herein we proposed a strategy for imprinting of a protein on the surface of nanoparticles using a metal chelating monomer. With lysozyme as a model protein template and Cu(2+) chelating N-(4-vinyl)-benzyl iminodiacetic acid as the coordination monomer along with other monomers, protein imprinted polymer nanoshells were formed over vinyl-modified silica nanoparticles via surface polymerization in high-dilution monomer solution.

Silica nanoparticle supported molecularly imprinted polymer layers with varied degrees of crosslinking for lysozyme recognition.

Surface imprinting over nanosized support materials is particularly suitable for protein templates, considering the problems with mass transfer limitation and low binding capacity. Previously we have demonstrated a strategy for surface protein imprinting over vinyl-modified silica nanopartiles with lysozyme as a model template by polymerization in high-dilution monomer solution to prevent macrogelation. Herein, the synthesis process was further studied toward enhancement of the imprinting performance by examining the effect of several synthesis conditions.

Enhanced lysozyme imprinting over nanoparticles functionalized with carboxyl groups for noncovalent template sorption.

Surface molecular imprinting, in particular over nanosized support materials, is very suitable for a template of bulky structure like protein. Inspired by the surface template immobilization method reported previously, we herein demonstrate an alternative strategy for enhancing specific recognition of core-shell protein-imprinted nanoparticles through prefunctionalizing the cores with noncovalent template sorption groups. For proof of this concept, silica nanoparticles chosen as the core materials were modified consecutively with 3-aminopropyltrimethoxysilane and maleic anhydride to introduce polymerizable double bonds and terminal carboxyl groups, hence capable of physically adsorbing the print protein.