Children with systemic lupus erythematosus (SLE) are at increased risk of developing kidney disease, termed childhood-onset lupus nephritis (cLN). Single-cell transcriptomics of dissociated kidney tissue has advanced our understanding of LN pathogenesis, but loss of spatial resolution prevents interrogation of in situ cellular interactions. Using a technical advance in spatial transcriptomics, we generated a spatially resolved, single-cell resolution atlas of kidney tissue from eight patients with cLN and four control individuals.
View Article and Find Full Text PDFACS Appl Mater Interfaces
October 2024
Ternary metal carbide TiAlC has been proposed as a metal gate material in logic semiconductor devices. It is a hard-to-etch material due to the low volatility of the etch byproducts. Here, a simple, highly controllable, and dry etching method for TiAlC has been first presented using nonhalogen N/H plasmas at low pressure (several Pa) and 20 °C.
View Article and Find Full Text PDFPD-1 is a key negative regulator of CD8 T cell activation and is highly expressed by exhausted T cells in cancer and chronic viral infection. Although PD-1 blockade can improve viral and tumor control, physiological PD-1 expression prevents immunopathology and improves memory formation. The mechanisms driving high PD-1 expression in exhaustion are not well understood and could be critical to disentangling its beneficial and detrimental effects.
View Article and Find Full Text PDFPurpose: Current monoclonal antibody-based treatment approaches for cutaneous T cell lymphoma (CTCL) rely heavily on the ability to identify a tumor specific target that is essentially absent on normal cells. Herein, we propose tumor associated glycoprotein-72 (TAG-72) as one such target. TAG-72 is a mucin-associated, truncated O-glycan that has been identified as a chimeric antigen receptor (CAR)-T cell target in solid tumor indications.
View Article and Find Full Text PDFObjective: To compare oocyte maturation rates and pregnancy outcomes in women with polycystic ovary syndrome (PCOS) undergoing biphasic in vitro maturation (capacitation in vitro maturation [CAPA-IVM]) with vs. without follicle-stimulating hormone (FSH) priming.
Design: Randomized, controlled, assessor-blinded trial.
Dengue hemorrhagic fever (DHF) is the most prevalent and fastest-growing vector-borne disease globally, with symptoms ranging from mild to severe and, in some cases, fatal. Quang Nam province in Vietnam can serve as a model for dengue epidemiological study, as it is an endemic region for DHF with a tropical climate, which significantly constrains the health system. However, there are very few epidemiological and microbiological reports on Dengue virus (DENV) serotypes in this region due to the limited availability of advanced surveillance infrastructure.
View Article and Find Full Text PDFThe CF group is well noted for being noninteractive with other functional groups. In this Note, we present a highly rigid model system containing a significant hydrogen bonding interaction between a charged N-H donor and a CF acceptor that challenges this accepted wisdom. Spectroscopic and single crystal X-ray crystallography data characterize this interaction, consistent with a weak to moderate hydrogen bond that would be difficult to observe in an intermolecular system.
View Article and Find Full Text PDFBackground: This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia.
Methods: Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention.
N Engl J Med
September 2024
Background: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection.
Methods: The systematic review was registered in PROSPERO (CRD42023468063).
Concurrent readout of sequence and base modifications from long unamplified DNA templates by Pacific Biosciences of California (PacBio) single-molecule sequencing requires large amounts of input material. Here we adapt Tn5 transposition to introduce hairpin oligonucleotides and fragment (tagment) limiting quantities of DNA for generating PacBio-compatible circular molecules. We developed two methods that implement tagmentation and use 90-99% less input than current protocols: (1) single-molecule real-time sequencing by tagmentation (SMRT-Tag), which allows detection of genetic variation and CpG methylation; and (2) single-molecule adenine-methylated oligonucleosome sequencing assay by tagmentation (SAMOSA-Tag), which uses exogenous adenine methylation to add a third channel for probing chromatin accessibility.
View Article and Find Full Text PDFResearch on metastatic cancer has been hampered by limited sample availability. Here we present the breast cancer post-mortem tissue donation program UPTIDER and show how it enabled sampling of a median of 31 (range: 5-90) metastases and 5-8 liquids per patient from its first 20 patients. In a dedicated experiment, we show the mild impact of increasing time after death on RNA quality, transcriptional profiles and immunohistochemical staining in tumor tissue samples.
View Article and Find Full Text PDFCysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors for a wide range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed "DrugMap," an atlas of cysteine ligandability compiled across 416 cancer cell lines.
View Article and Find Full Text PDFAn extremely bulky -terphenyl bis(aniline), -CH{CH[N(H)TCHP]-2} (TCHP = 2,4,6-tricyclohexylphenyl) TerphH, has been developed. Deprotonation of a less bulky analogue, TerphH (Dip = 2,6-diisopropylphenyl), with BePh affords the bimetallic system, [(BePh)(μ-Terph)] . Treating either TerphH or TerphH with Mg{CH(SiMe)} gives the monomeric bis(anilide) complexes [Mg(Terph)] (Ar = Dip , TCHP ) which display rare examples of η-arene coordination to the metal center.
View Article and Find Full Text PDFA central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma. T cell exhaustion, resulting from chronic antigen exposure in the tumour microenvironment, is a major driver of ICB resistance. Here, we show that CD38, an ecto-enzyme involved in nicotinamide adenine dinucleotide (NAD) catabolism, is highly expressed in exhausted CD8 T cells in melanoma and is associated with ICB resistance.
View Article and Find Full Text PDFBackground: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation.
Methods: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma.
A combined study using the surface-enhanced Raman scattering (SERS) technique and quantum chemical calculations was carried out to elucidate the adsorption behavior of sulfathiazole, an antibiotic drug, on gold nanoparticles. The tetrahedral Au cluster was used as a simple model to mimic a nanostructured gold surface. Computations using density functional theory with the PBE functional were performed in both the gas phase and aqueous medium using a continuum model.
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