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Abstract: An early event in the genesis of follicular lymphoma (FL) is the acquisition of new glycosylation motifs in the B-cell receptor (BCR) due to gene rearrangement and/or somatic hypermutation. These N-linked glycosylation motifs (N-motifs) contain mannose-terminated glycans and can interact with lectins in the tumor microenvironment, activating the tumor BCR pathway. N-motifs are stable during FL evolution, suggesting that FL tumor cells are dependent on them for their survival. Here, we investigated the dynamics and potential impact of N-motif prevalence in FL at the single-cell level across distinct tumor sites and over time in 17 patients. Although most patients had acquired at least 1 N-motif as an early event, we also found (1) cases without N-motifs in the heavy or light chains at any tumor site or time point and (2) cases with discordant N-motif patterns across different tumor sites. Inferring phylogenetic trees of the patients with discordant patterns, we observed that both N-motif-positive and N-motif-negative tumor subclones could be selected and expanded during tumor evolution. Comparing N-motif-positive with N-motif-negative tumor cells within a patient revealed higher expression of genes involved in the BCR pathway and inflammatory response, whereas tumor cells without N-motifs had higher activity of pathways involved in energy metabolism. In conclusion, although acquired N-motifs likely support FL pathogenesis through antigen-independent BCR signaling in most patients with FL, N-motif-negative tumor cells can also be selected and expanded and may depend more heavily on altered metabolism for competitive survival., (© 2023 by The American Society of Hematology.)

Mismanaged municipal solid waste (MSW), the major source of plastics pollution and a key contributor to climate forcing, in Global South cities poses public health and environmental problems. This study analyses the first consistent and quality assured dataset available for cities distributed worldwide, featuring a comprehensive set of solid waste management performance indicators (Wasteaware Cities Benchmark Indicators - WABI). Machine learning (multivariate random forest) and univariate non-linear regression are applied, identifying best-fit converging models for a broad range of explanatory socioeconomic variables. These proxies describe in a variety of ways generic levels of progress, such as Gross Domestic Product - Purchasing Power per capita, Social Progress Index (SPI) and Corruption Perceptions Index. Specifically, the research tests and quantitatively confirms a long-standing, yet unverified, hypothesis: that variability in cities' performance on MSW can be accounted for by socioeconomic development indices. The results provide a baseline for measuring progress as cities report MSW performance for the sustainable development goal SDG11.6.1 indicator: median rates of controlled recovery and disposal are approximately at 45 % for cities in low-income countries, 75 % in lower-middle, and 100 % for both upper-middle and high-income. Casting light on aspects beyond the SDG metric, on the quality of MSW-related services, show that improvements in service quality often lag improvements in service coverage. Overall, the findings suggest that progress in collection coverage, and controlled recovery and disposal has already taken place in low- and middle-income cities. However, if cities aspire to perform better on MSW management than would have been anticipated by the average socioeconomic development in their country, they should identify ways to overcome systemic underlying failures associated with that socioeconomic level. Most alarmingly, 'business as usual' development would substantially increase their waste generation per capita unless new policies are found to promote decoupling., Competing Interests: Declaration of competing interest Dr. Costas Velis reports a relationship with International Solid Waste Association (ISWA) that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Dr. Costas Velis and Prof. David C Wislon, Prof. Sue M Grimes are actively involved in the waste, resources and circular economy sector in research, advising, scholarship and consultancy capacities. Mr. Andrew Whiteman is regularly providing consultancy services for the sector worldwide., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Tumor heterogeneity complicates biomarker development and fosters drug resistance in solid malignancies. In lymphoma, our knowledge of site-to-site heterogeneity and its clinical implications is still limited. Here, we profiled 2 nodal, synchronously acquired tumor samples from 10 patients with follicular lymphoma (FL) using single-cell RNA, B-cell receptor (BCR) and T-cell receptor sequencing, and flow cytometry. By following the rapidly mutating tumor immunoglobulin genes, we discovered that BCR subclones were shared between the 2 tumor sites in some patients, but in many patients, the disease had evolved separately with limited tumor cell migration between the sites. Patients exhibiting divergent BCR evolution also exhibited divergent tumor gene-expression and cell-surface protein profiles. While the overall composition of the tumor microenvironment did not differ significantly between sites, we did detect a specific correlation between site-to-site tumor heterogeneity and T follicular helper (Tfh) cell abundance. We further observed enrichment of particular ligand-receptor pairs between tumor and Tfh cells, including CD40 and CD40LG, and a significant correlation between tumor CD40 expression and Tfh proliferation. Our study may explain discordant responses to systemic therapies, underscores the difficulty of capturing a patient's disease with a single biopsy, and furthers our understanding of tumor-immune networks in FL., (© 2021 by The American Society of Hematology.)

Follicular lymphoma (FL) is a low-grade B-cell malignancy that transforms into a highly aggressive and lethal disease at a rate of 2% per year. Perfect isolation of the malignant B-cell population from a surgical biopsy is a significant challenge, masking important FL biology, such as immune checkpoint coexpression patterns. To resolve the underlying transcriptional networks of follicular B-cell lymphomas, we analyzed the transcriptomes of 34 188 cells derived from 6 primary FL tumors. For each tumor, we identified normal immune subpopulations and malignant B cells, based on gene expression. We used multicolor flow cytometry analysis of the same tumors to confirm our assignments of cellular lineages and validate our predictions of expressed proteins. Comparison of gene expression between matched malignant and normal B cells from the same patient revealed tumor-specific features. Malignant B cells exhibited restricted immunoglobulin (Ig) light chain expression (either Igκ or Igλ), as well the expected upregulation of the BCL2 gene, but also downregulation of the FCER2 , CD52 , and major histocompatibility complex class II genes. By analyzing thousands of individual cells per patient tumor, we identified the mosaic of malignant B-cell subclones that coexist within a FL and examined the characteristics of tumor-infiltrating T cells. We identified genes coexpressed with immune checkpoint molecules, such as CEBPA and B2M in regulatory T (Treg) cells, providing a better understanding of the gene networks involved in immune regulation. In summary, parallel measurement of single-cell expression in thousands of tumor cells and tumor-infiltrating lymphocytes can be used to obtain a systems-level view of the tumor microenvironment and identify new avenues for therapeutic development., (© 2019 by The American Society of Hematology.)

In mixed wastewater streams, the presence of metal ions can retard the destruction of organic contaminants and the efficiency of recovery of the metal is reduced by the presence of organic species. The reduction in the efficiency of these methods is due to the formation of complexes between the organic species and the metal ions in solution. Results are presented for copper-2,4,5-T system in which both effects occur. A photolytic cell alone can achieve the complete degradation of 2,4,5-T, in the presence of TiO(2) or H(2)O(2), at pH 3.5. The addition of Cu(II) ions, however, retard the degradation of 2,4,5-T and complete mineralisation of 2,4,5-T was not achieved and the system also leaves Cu(II) ions in solution. An electrolytic cell alone can be used to recover copper in pH range 1.5-4.5 but is not capable of achieving complete disappearance of 2,4,5-T by anodic oxidation. A combined photolytic-electrolytic system is capable of achieving simultaneous destruction of 2,4,5-T and recovery of copper from mixed wastewater streams at pH 3.5. The percentage destruction of 2,4,5-T and the recovery of copper can be increased further by using a combined photolytic and an activated carbon concentrator cell system. This system can achieve the simultaneous recovery of copper and the degradation of 2,4,5-T without the use of an additional oxidants or catalysts.