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The use of RNA sequencing from wastewater samples is a valuable way for estimating infection dynamics and circulating lineages of SARS-CoV-2. This approach is independent from testing individuals and can therefore become the key tool to monitor this and potentially other viruses. However, it is equally important to develop easily accessible and scalable tools which can highlight critical changes in infection rates and dynamics over time across different locations given sequencing data from wastewater. Here, we provide an analysis of lineage dynamics in Berlin and New York City using wastewater sequencing and present PiGx SARS-CoV-2, a highly reproducible computational analysis pipeline with comprehensive reports. This end-to-end pipeline includes all steps from raw data to shareable reports, additional taxonomic analysis, deconvolution and geospatial time series analyses. Using simulated datasets (in silico generated and spiked-in samples) we could demonstrate the accuracy of our pipeline calculating proportions of Variants of Concern (VOC) from environmental as well as pre-mixed samples (spiked-in). By applying our pipeline on a dataset of wastewater samples from Berlin between February 2021 and January 2022, we could reconstruct the emergence of B.1.1.7(alpha) in February/March 2021 and the replacement dynamics from B.1.617.2 (delta) to BA.1 and BA.2 (omicron) during the winter of 2021/2022. Using data from very-short-reads generated in an industrial scale setting, we could see even higher accuracy in our deconvolution. Lastly, using a targeted sequencing dataset from New York City (receptor-binding-domain (RBD) only), we could reproduce the results recovering the proportions of the so-called cryptic lineages shown in the original study. Overall our study provides an in-depth analysis reconstructing virus lineage dynamics from wastewater. While applying our tool on a wide range of different datasets (from different types of wastewater sample locations and sequenced with different methods), we show that PiGx SARS-CoV-2 can be used to identify new mutations and detect any emerging new lineages in a highly automated and scalable way. Our approach can support efforts to establish continuous monitoring and early-warning projects for detecting SARS-CoV-2 or any other pathogen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

A wide range of organic micropollutants (n = 163) representing several compound categories (pharmaceuticals, pesticides, per- and polyfluorinated alkyl substances, flame retardants, phthalates, food additives, drugs and benzos) were analysed in water samples from the Göta Älv river (Sweden's second largest source water). The sampling also included raw water and finished drinking water from seven drinking water treatment plants and in addition a more detailed sampling at one of the treatment plants after six granulated active carbon filters of varying operational ages. In total, 27 organic micropollutants were detected, with individual concentrations ranging from sub ng L -1 levels to 54 ng L -1 . The impact of human activities along the flow path was reflected by increased concentrations downstream the river, with total concentrations ranging from 65 ng L -1 at the start of the river to 120 ng L -1 at the last sampling point. The removal efficiency was significantly (p = 0.014; one-sided t-test) higher in treatment plants that employed granulated active carbon filters (n = 4; average 60%) or artificial infiltration (n = 1; 65%) compared with those that used a more conventional treatment strategy (n = 2; 38%). The removal was also strongly affected by the operational age of the carbon filters. A filter with an operational age of 12 months with recent addition of ~10% new material showed an average removal efficiency of 92%, while a 25-month old filter had an average of 76%, and an even lower 34% was observed for a 71-month old filter. The breakthrough in the carbon filters occurred in the order of dissolved organic carbon, per- and polyfluorinated alkyl substances and then other organic micropollutants. The addition of fresh granulated active carbon seemed to improve the removal of hydrophobic organic compounds, particularly dissolved organic carbon and per- and polyfluorinated alkyl substances., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Syringe filters are used to separate solids from liquids prior to analysis of poly- and perfluoroalkyl substances (PFASs). This is a critical step in sample preparation, as losses of PFASs to the filter material can be significant and lead to underestimation. This study evaluated losses of 21 PFASs in three different matrices (methanol, MilliQ water, and water containing 10 mg L -1 dissolved organic carbon (DOC)) to six different types of syringe filter (0.45 and 0.22 μm). Regarding sample matrix, the lowest average ∑ 21 PFAS losses were observed in methanol (13%), followed by DOC water (19%) and MilliQ water (26%). Regarding syringe filter material, the lowest average losses of ∑ 21 PFAS in DOC water and MilliQ water were observed for a recycled cellulose filter (average losses 16% and 21%, respectively), while a polypropylene filter had the lowest ∑ 21 PFAS losses in methanol (9%). A smaller polyethersulfone (PES) filter (0.22 μm, 17 mm Ø) showed significantly (p < 0.05) lower ∑ 21 PFAS losses in DOC water (on average 7.3%) than a larger PES filter (0.45 μm, 37 mm Ø) (23%). In DOC water, losses to the filter increased by 3.8%, 5.1%, and 8.4% per CF 2 -moiety for C 3 -C 11 perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates (PFSAs), and fluorotelomer sulfonic acids (FTSAs), respectively. Comparing different functional groups of PFASs, losses increased as follows: PFCAs < PFSAs < FTSAs < perfluorooctanesulfonamides (FOSAs). Thus, care is needed when including filtration in PFAS analysis, since losses can be significant (up to 100%) depending on the type of syringe filter, target PFAS, and matrix., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Persistent NF-κB activation is a hallmark of the malignant Hodgkin/Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL). Genomic lesions, Epstein-Barr virus infection, soluble factors, and tumor-microenvironment interactions contribute to this activation. Here, in an unbiased approach to identify the cHL cell-secreted key factors for NF-κB activation, we have dissected the secretome of cultured cHL cells by chromatography and subsequent mass spectrometry. We identified lymphotoxin-α (LTA) as the causative factor for autocrine and paracrine activation of canonical and noncanonical NF-κB in cHL cell lines. In addition to inducing NF-κB, LTA promotes JAK2/STAT6 signaling. LTA and its receptor TNFRSF14 are transcriptionally activated by noncanonical NF-κB, creating a continuous feedback loop. Furthermore, LTA shapes the expression of cytokines, receptors, immune checkpoint ligands and adhesion molecules, including CSF2, CD40, PD-L1/PD-L2, and VCAM1. Comparison with single-cell gene-activity profiles of human hematopoietic cells showed that LTA induces genes restricted to the lymphoid lineage, as well as those largely restricted to the myeloid lineage. Thus, LTA sustains autocrine NF-κB activation, impacts activation of several signaling pathways, and drives expression of genes essential for microenvironmental interactions and lineage ambiguity. These data provide a robust rationale for targeting LTA as a treatment strategy for cHL patients., (© 2019 by The American Society of Hematology.)

In mouse, the oocyte-to-embryo transition entails converting a highly differentiated oocyte to totipotent blastomeres. This transition is driven by degradation of maternal mRNAs, which results in loss of oocyte identity, and reprogramming of gene expression during the course of zygotic gene activation, which occurs primarily during the two-cell stage and confers blastomere totipotency. Full-grown oocytes are transcriptionally quiescent and mRNAs are remarkably stable in oocytes due to the RNA-binding protein MSY2, which stabilizes mRNAs, and low activity of the 5' and 3' RNA degradation machinery. Oocyte maturation initiates a transition from mRNA stability to instability due to phosphorylation of MSY2, which makes mRNAs more susceptible to the RNA degradation machinery, and recruitment of dormant maternal mRNAs that encode for critical components of the 5' and 3' RNA degradation machinery. Small RNAs (miRNA, siRNA, and piRNA) play little, if any, role in mRNA degradation that occurs during maturation. Many mRNAs are totally degraded but a substantial fraction is only partially degraded, their degradation completed by the end of the two-cell stage. Genome activation initiates during the one-cell stage, is promiscuous, low level, and genome wide (and includes both inter- and intragenic regions) and produces transcripts that are inefficiently spliced and polyadenylated. The major wave of genome activation in two-cell embryos involves expression of thousands of new genes. This unique pattern of gene expression is the product of maternal mRNAs recruited during maturation that encode for transcription factors and chromatin remodelers, as well as dramatic changes in chromatin structure due to incorporation of histone variants and modified histones., (© 2015 Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to assess the area at risk (AAR) in ST-segment elevation myocardial infarction with 2 different cardiac magnetic resonance (CMR) imaging methods and to compare them with the validated angiographic Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Score (APPROACH-score) in a large consecutive patient cohort., Background: Edema imaging with T(2)-weighted CMR and the endocardial surface area (ESA) assessed by late gadolinium enhancement have been introduced as relatively new methods for AAR assessment in ST-segment elevation myocardial infarction. However, data on the utility and validation of these techniques are limited., Methods: A total of 197 patients undergoing primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction were included. AAR (assessed with T(2)-weighted edema imaging and the ESA method), infarct size, and myocardial salvage (AAR minus infarct size) were determined by CMR 2 to 4 days after primary angioplasty. Angiographic AAR scoring was performed by use of the APPROACH-score. All measurements were done offline by blinded observers., Results: The AAR assessed by T(2)-weighted imaging showed good correlation with the angiographic AAR (r = 0.87; p < 0.001), whereas the ESA showed only a moderate correlation either to T(2)-weighted imaging (r = 0.56; p < 0.001) or the APPROACH-score (r = 0.44; p < 0.001). Mean AAR by ESA (20.0 ± 11.7% of left ventricular mass) was significantly (p < 0.001) smaller than the AAR assessed by T(2)-weighted imaging (35.6 ± 10.9% of left ventricular mass) or the APPROACH-score (27.9 ± 10.5% of left ventricular mass) and showed a significant negative dependence on myocardial salvage index. In contrast, no dependence of T(2)-weighted edema imaging or the APPROACH-score on myocardial salvage index was seen., Conclusions: The AAR can be reliably assessed by T(2)-weighted CMR, whereas assessment of the AAR by ESA seems to be dependent on the degree of myocardial salvage, thereby underestimating the AAR in patients with high myocardial salvage such as aborted infarction. Thus, assessment of the AAR with the ESA method cannot be recommended. (Myocardial Salvage and Contrast Dye Induced Nephropathy Reduction by N-Acetylcystein [LIPSIA-N-ACC]; NCT00463749)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To characterise arterio-venous anastomoses (AVA) in monochorionic (MC) placentae and determine (i) whether shared cotyledons lie beneath the co-termination of an artery from one twin and a vein to the contralateral twin and (ii) whether all AVA can be detected by visual inspection of the chorionic plate., Methods: Vascular casts were made of 15 MC placentae. The number of typical AVAs suspected visually before digestion was compared with the number of AVAs identified after acid digestion., Results: Thirty-three of 67 (49%) suspected typical AVAs were confirmed as typical after casting. There were five false positives and no false negatives. The remainder were classified as atypical AVAs, found in > or =90% of MC placentae. Type I (small vascular connections between two apparently normal cotyledons not seen before casting) and Type II (shared cotyledons arising within larger apparently normal cotyledons) atypical AVAs were found in 53% and 73% of placentae, respectively., Conclusions: Only half the shared cotyledons in MC placentae are characterised by co-termination of an artery and vein on the chorionic plate. We report the existence of deep anastomoses beneath the chorionic plate that cannot be visualised by chorionic plate inspection. These findings have implications for laser treatment of twin-twin transfusion syndrome.