Transformer-based AI technology improves early ovarian cancer diagnosis using cfDNA methylation markers.

Epithelial ovarian cancer (EOC) is the deadliest women's cancer and has a poor prognosis. Early detection is the key for improving survival (a 5-year survival rate in stage I/II is over 70% compared to that of 25% in stage III/IV) and can be achieved through methylation markers from circulating cell-free DNA (cfDNA) using a liquid biopsy. In this study, we first identify top 500 EOC markers differentiating EOC from healthy female controls from 3.3 million methylome-wide CpG sites and validated them in 1,800 independent cfDNA samples. We then utilize a pretrained AI transformer system called MethylBERT to develop an EOC diagnostic model which achieves 80% sensitivity and 95% specificity in early-stage EOC diagnosis. We next develop a simple digital droplet PCR (ddPCR) assay which archives good performance, facilitating early EOC detection.

PD1+CD4+ T cells promote receptor editing and suppress autoreactivity of CD19+CD21low B cells within the lower respiratory airways in adenovirus pneumonia.

Human adenovirus (HAdV) pneumonia poses a major health burden for young children, however, factors that contribute to disease severity remain elusive. We analyzed immune cells from bronchoalveolar lavage (BAL) of children with HAdV pneumonia and found that CD19+CD21low B cells were significantly enriched in the BAL and were associated with increased autoantibody concentrations and disease severity. Myeloid cells, PD-1+CD4+ T helper cells and CD21low B cells formed tertiary lymphoid structures within the respiratory tracts. Myeloid cells promoted autoantibody production by expressing high amounts of B cell activating factor (BAFF). In contrast, PD-1+CD4+ T helper cells induced production of IgG1 and IgG3 antibodies but suppressed autoreactive IgGs by initiating B cell receptor editing. In summary, this study reveals cellular components involved in protective versus autoreactive immune pathways in the respiratory tract, and these findings provide potential therapeutic targets for severe HAdV lower respiratory tract infections.

Virus surrogates throughout a full-scale advanced water reuse system.

Water reuse as an alternative water supply is increasing throughout the world due to water stress and scarcity; however, there are no standard practices for monitoring virus pathogens in such systems. This study aimed to identify suitable surrogates for virus fate, transport, and removal throughout a water reuse scheme. Various microbial targets (11 viruses, two phage, and three bacteria) were monitored using molecular and culture methods across all treatment stages in a wastewater reclamation facility and advanced water treatment facility. Criteria were established for identifying suitable surrogates, which included reliable detection, observable fate and transport, calculable log-reduction values (LRVs), correlations with other targets, and various morphological types. In total, five viruses (PMMoV, AiV, GII NoV, AdV, FRNA GII) met these stringent criteria and were suggested as potential virus surrogates. These surrogates enabled successful comparison of assigned versus actual LRVs throughout a water reuse scheme. Results suggest that virus pathogens are effectively removed throughout water reuse treatment and the suggested surrogates can be utilized for monitoring treatment performance and ensuring public health safety. This study provides a framework that water utilities across the world can reference for establishing virus monitoring practices.

Susceptibility of TSPAN5 polymorphisms to Kawasaki disease and immunoglobulin therapy resistance in southern Chinese children.

Kawasaki disease (KD) is a condition characterized by acute multi-system vasculitis and high fever in infants and children. Intravenous immunoglobulin (IVIG) is the established therapeutic approach of KD,foralleviating inflammation and mitigate the risk of arterial wall dilation and the development of coronary artery aneurysms (CAA). But almost 20% of the patients developed resistance to IVIG and displayed persistent fever after standard primary treatment. TSPAN5, belonging to the Tetraspanin family, has been demonstrated to modulate innate immunity in a range of human diseases. It accomplishes this by engaging with integrins and actively participating in the process of infection recognition. However, its relevance to susceptibility and IVIG therapy response of KD was unexposed. In the present study, our Integrative analysis of KD transcriptomic data and GTEx data revealed that the eQTL rs12504972 might modify the downregulation of TSPAN5 in KD patients. Moreover, our findings suggest a potential association between TSPAN5/rs12504972 and an elevated susceptibility as well as IVIG resistance among patients with Kawasaki disease in southern China. The results provided a new insight that TSPAN5 triggered KD susceptibility and resistance of IVIG therapy on the genomic level.

ADAM22 acts as a novel predictive biomarker for unfavorable prognosis and facilitates metastasis via PI3K/AKT signaling pathway in nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of epithelial malignancy known for its high likelihood of metastasizing to distant organs, which remains the primary obstacle in the treatment of NPC. The present study aimed to identify potential intervention target for NPC metastasis. METHODS: The differentially expressed genes (DEGs) were firstly analyzed and intersected across various NPC related datasets in the Gene Expression Omnibus database. Subsequently, various techniques including quantitative polymerase chain reaction (qPCR), western blotting, immunohistochemistry, migration and invasion assays, in conjunction with bioinformatics and prognostic modeling, were utilized to elucidate the role of candidate genes in NPC metastasis. RESULTS: We discerned the gene a disintegrin and metalloprotease 22 (ADAM22) as a distinct and significant factor in the progression and metastasis of NPC through five datasets. The elevated expression of ADAM22 was observed in clinical tissue and plasma samples with advanced NPC, as well as in high metastatic cells. Furthermore, we highlighted its essential role in a prognostic model that demonstrated strong prediction performance for NPC. Notably, overexpression of ADAM22 was found to enhance the aggressiveness and epithelial-mesenchymal transition (EMT) of low metastatic NPC cells, whereas the downregulation of ADAM22 resulted in suppressed effect in high metastatic cells. Delving into the mechanism, ADAM22 activated the PI3K/Akt signaling pathway through the mediation of Rac Family Small GTPase 2 (RAC2), thereby facilitating EMT and metastasis in NPC. CONCLUSIONS: The study provided pioneering insights that ADAM22 had the potential to act as an oncogene by promoting EMT and metastasis of NPC through the RAC2-mediated PI3K/Akt signaling pathway. Thus, ADAM22 could serve as a novel prognostic indicator in NPC.

A comparative study of flow cytometry-sorted communities and shotgun viral metagenomics in a Singapore municipal wastewater treatment plant.

Traditional or "bulk" viral enrichment and amplification methods used in viral metagenomics introduce unavoidable bias in viral diversity. This bias is due to shortcomings in existing viral enrichment methods and overshadowing by the more abundant viral populations. To reduce the complexity and improve the resolution of viral diversity, we developed a strategy coupling fluorescence-activated cell sorting (FACS) with random amplification and compared this to bulk metagenomics. This strategy was validated on both influent and effluent samples from a municipal wastewater treatment plant using the Modified Ludzack-Ettinger (MLE) process as the treatment method. We found that DNA and RNA communities generated using bulk samples were mostly different from those derived following FACS for both treatments before and after MLE. Before MLE treatment, FACS identified five viral families and 512 viral annotated contigs. Up to 43% of mapped reads were not detected in bulk samples. Nucleo-cytoplasmic large DNA viral families were enriched to a greater extent in the FACS-coupled subpopulations compared with bulk samples. FACS-coupled viromes captured a single-contig viral genome associated with Anabaena phage, which was not observed in bulk samples or in FACS-sorted samples after MLE. These short metagenomic reads, which were assembled into a high-quality draft genome of 46 kbp, were found to be highly dominant in one of the pre-MLE FACS annotated virome fractions (57.4%). Using bulk metagenomics, we identified that between Primary Settling Tank and Secondary Settling Tank viromes, Virgaviridae, Astroviridae, Parvoviridae, Picobirnaviridae, Nodaviridae, and Iridoviridae were susceptible to MLE treatment. In all, bulk and FACS-coupled metagenomics are complementary approaches that enable a more thorough understanding of the community structure of DNA and RNA viruses in complex environmental samples, of which the latter is critical for increasing the sensitivity of detection of viral signatures that would otherwise be lost through bulk viral metagenomics.