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This study underscores the crucial role of seal impressions on Sino-Russian treaties, viewing the indifference of seal-created visual information as a significant defect in current treaty scholarship. This research proposes that the analysis of material seals holds equal importance to the textual examination of written articles in comprehending SinoRussian diplomatic culture. The mandatory use of official seals for signing bilateral treaties in both the Qing and Russian Empires is deeply rooted in their unique civilizations and traditions. From this background, the political culture of these empires guided the treaty negotiators to perceive the seal impressions on treaties not only as mutual commitments to fulfilling the treaty promises but also as a non-linguistic means to engage with their respective relationship positions. As a result, both written articles and visual sigillography are invaluable as primary sources in treaty research.

Background: Paraneoplastic antibodies are implicated in heterogeneous clinical presentations. Commercial immunoassays include indirect immunofluorescence (IIF), and line immunoblot (LIB). LIB can be associated with false positives, and unfortunately, further confirmatory assays are not readily available in diagnostic laboratories., Objectives: To determine frequency of positive LIB on serum or cerebrospinal fluid (CSF) using EUROLine paraneoplastic neurological syndromes (PNS) 12 Ag Test kit (EuroImmun, Germany) and establish concordance with IIF on Nova Lite kit (Inova Diagnostics, United States) and clinical presentation., Methods: A retrospective analysis of all LIB performed over a four-year period was undertaken. Healthy control samples were also analysed with IIF and LIB., Results: Two thousand and eighty-one LIB samples were processed, 91 (4.4%) were positive from 69 patients with a median age of 64 years. There were 37 females (53.6%). Some samples had two antibody specificities ( n  = 6, 6.6%). Of those with one antibody, GAD65 ( n  = 22), Yo ( n  = 19), SOX1 ( n  = 17) and amphiphysin ( n  = 14) were most frequent. Of the positive LIBs, 80 (87.9%) had concurrent IIF and eight samples (10%) had a typical IIF pattern. Clinical relevance of a positive LIB, irrespective of IIF, was seen in 15/91 samples (14.3%) from nine patients; GAD65 ( n  = 3), Hu ( n  = 2), amphiphysin ( n  = 1), Yo ( n  = 1), Tr ( n  = 1) and CV2 ( n  = 1). Of the 71 healthy controls, five (7.0%) had a positive LIB: medium band ( n  = 4, 5.6%: amphiphysin, CV2, SOX1 and Yo) and strong band ( n  = 1, 1.4%: Yo). All IIF were negative. On average, signal intensity (SI) was higher in those with disease (SI 77.3/very strong band) compared to those without (SI 28.6/strong band) and healthy controls (SI 2/negative band) ( p  < 0.0001)., Discussion: LIB has a high false positive rate, and in this cohort, there were more false than true positive results. The assay must be used in those with a high clinical suspicion for PNS. While the commercial IIF kit is a useful test, it is insufficient to be used as a screening strategy in isolation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Ali, Cecchin, Burfoot, Chia, Ravindran, Field, King, Pucar and Banovic.)

Abstract: DNMT3A and TET2 are epigenetic regulator genes commonly mutated in age-related clonal hematopoiesis (CH). Despite having opposed epigenetic functions, these mutations are associated with increased all-cause mortality and a low risk for progression to hematologic neoplasms. Although individual impacts on the epigenome have been described using different model systems, the phenotypic complexity in humans remains to be elucidated. Here, we make use of a natural inflammatory response occurring during coronavirus disease 2019 (COVID-19), to understand the association of these mutations with inflammatory morbidity (acute respiratory distress syndrome [ARDS]) and mortality. We demonstrate the age-independent, negative impact of DNMT3A mutant (DNMT3Amt) CH on COVID-19-related ARDS and mortality. Using single-cell proteogenomics we show that DNMT3A mutations involve myeloid and lymphoid lineage cells. Using single-cell multiomics sequencing, we identify cell-specific gene expression changes associated with DNMT3A mutations, along with significant epigenomic deregulation affecting enhancer accessibility, resulting in overexpression of interleukin-32 (IL-32), a proinflammatory cytokine that can result in inflammasome activation in monocytes and macrophages. Finally, we show with single-cell resolution that the loss of function of DNMT3A is directly associated with increased chromatin accessibility in mutant cells. Hence, we demonstrate the negative prognostic impact of DNMT3Amt CH on COVID-19-related ARDS and mortality. DNMT3Amt CH in the context of COVID-19, was associated with inflammatory transcriptional priming, resulting in overexpression of IL32. This overexpression was secondary to increased chromatic accessibility, specific to DNMT3Amt CH cells. DNMT3Amt CH can thus serve as a potential biomarker for adverse outcomes in COVID-19., (© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)