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Wildtype Heterogeneity Contributes to Clonal Variability in Genome Edited Cells
Abstract: Genome editing tools such as CRISPR/Cas9 enable the rapid and precise manipulation of genomes. CRISPR-based genome editing has greatly simplified the study of gene function in cell lines, but its widespread use has also highlighted challenges of reproducibility. Phenotypic variability among different knockout clones of the same gene is a common problem confounding the establishment of robust genotype-phenotype correlations. Optimized genome editing protocols to enhance reproducibility include measures to reduce off-target effects. However, even if current state-of-the-art protocols are applied phenotypic variability is frequently observed. Here we identify heterogeneity of wild-typ...
Eculizumab as a Treatment for C3 Glomerulopathy: a Single-center Retrospective Study
Abstract: Background C3 Glomerulopathy (C3G) is a rare glomerular disease caused by dysregulation of the complement pathway. Based on its pathophysiology, treatment with the monoclonal antibody eculizumab targeting complement C5 may be a therapeutic option. Due to the rarity of the disease, observational data on the clinical response to eculizumab treatment is scarce. Methods Fourteen patients (8 female, 57%) treated for C3 glomerulopathy at the medical center of the University of Freiburg between 2013 and 2022 were included. Subjects underwent biopsy before enrollment. Histopathology, clinical data, and response to eculizumab treatment were analyzed. Key parameters to determine the primary ...
Clinical Covariates Influencing Clinical Outcomes in Primary Membranous Nephropathy
Abstract: Background Primary membranous nephropathy (PMN) frequently causes nephrotic syndrome and declining kidney function. Disease progression is likely modulated by patient-specific and therapy-associated factors awaiting characterization. These cofactors may facilitate identification of risk groups and could result in more individualized therapy recommendations. Methods In this single-center retrospective observational study, we analyze the effect of patient-specific and therapy-associated covariates on proteinuria, hypoalbuminemia, and estimated glomerular filtration rate (eGFR) in 74 patients diagnosed with antibody positive PMN and nephrotic-range proteinuria (urine-protein-creatinin...
The Ocean and Cryosphere in a Changing Climate
The Intergovernmental Panel on Climate Change (IPCC) is the leading international body for assessing the science related to climate change. It provides policymakers with regular assessments of the scientific basis of human-induced climate change, its impacts and future risks, and options for adaptation and mitigation. This IPCC Special Report on the Ocean and Cryosphere in a Changing Climate is the most comprehensive and up-to-date assessment of the observed and projected changes to the ocean and cryosphere and their associated impacts and risks, with a focus on resilience, risk management response options, and adaptation measures, considering both their potential and limitations. It brings together knowledge on physical and biogeochemical changes, the interplay with ecosystem changes, and the implications for human communities. It serves policymakers, decision makers, stakeholders, and all interested parties with unbiased, up-to-date, policy-relevant information. This title is also available as Open Access on Cambridge Core.
