Pristine levels of suspended sediment in large German river channels during the Anthropocene?

Suspended sediment is an integral part of riverine transport and functioning that has been strongly altered during the Anthropocene due to the overwhelming human pressure on soils, sediments, and the water cycle. Understanding the controls of changing suspended sediment in rivers is therefore vital for effective management strategies. Here we present results from a trend analysis of suspended sediments covering 62 monitoring stations along the German waterways (catchment sizes range between 2000 and 160 000 km2) with more than 440 000 water samples taken between 1990 and 2010. Based on daily monitoring of suspended sediment concentration (SSC), we found significant declines in mean annual SSC and annual suspended sediment loads (SSLs) at 49 of 62 monitoring stations totaling −0.92 mg L−1 yr−1. At some stations decreases during the 20 years represent up to 50 % of the long-term average SSC. Significant decreases in SSC are associated with declining SSL despite an increase in sheet and rill erosion by almost 150 % derived from modeling due to changes in land use and management as well as rainfall erosivity. The contemporary suspended sediment loads of the Rhine at the German–Dutch border are approaching the natural base level of ∼1 Mt yr−1, which was reached by the Rhine during the mid-Holocene when the suspended sediment load was adjusted to the Holocene climatic conditions and before the onset of increased loads due to human-induced land use changes in the Rhine catchment. At this point we can only speculate regarding potential reasons for a decline in sediment transport in larger rivers despite erosion increase. We argue that increased sediment retention in upstream headwaters is presumably the major reason for declining SSC in the large river channels studied.</p

Immune checkpoint expression in HNSCC patients before and after definitive chemoradiotherapy

Background Primary platinum-based chemoradiotherapy (CRT) remains the treatment of choice for nonresectable squamous cell carcinoma of the head and neck (HNSCC). Immune-checkpoint modulators are used as palliative therapy and studied in combination with definitive CRT. However, the immunological changes by CRT need yet to be understood. Methods A cohort consisting of 67 paired tissue biopsies (N = 134) of HNSCC patients before and after CRT was created. The expression of PD-1, PD-L1, and CD27 of tumor and immune cells by immunohistochemistry was evaluated. Results PD-L1 expression on immune cells of non-responders was significantly lower before CRT (P = .008). CD27 was expressed only on immune cells and not on cancer cells. A significant lower CD27-expression score was observed following CRT (P = .019). Conclusions Conventional CRT changes the expression of CD27 in the tumor microenvironment. Whether this is due to a loss of expression or a reduction of CD27+ cells must be evaluated in further analyses

Surgical Treatment of Carcinomas of the Oral Minor Salivary Glands : Oncological Outcome in Dependence of Tumor Entity and Therapeutic Strategies

The aim of this study was to analyze the clinical outcomes of three types of minor salivary gland carcinomas (adenoid-cystic carcinomas (ACC), adeno carcinomas not otherwise specified (AC-NOS), and mucoepidermoid carcinomas (MEC)) after primary surgical therapy. A retrospective cohort study was designed and patients with cancer of the minor oral salivary glands treated in our department in the years 2011 to 2022 were included. Clinicopathological data were evaluated to compare overall survival and progression-free survival between the entities. Eighty-one patients were included. The rates of cervical metastases were 38.9% for ACC, 25% for MEC, and 9.1% for AC-NOS. ACC exhibited significantly higher rates of local and systemic disease recurrence (p = 0.02), and the presence of neck node metastases was confirmed as an independent prognostic factor for progressionfree survival (p = 0.014). Treatment success in terms of oncological outcome varied significantly between the different entities and implies different treatment regimens for each tumor entity

Peripapillary retinal nerve fiber layer profile in relation to refractive error and axial length : results from the Gutenberg Health Study

Purpose: To investigate the retinal nerve fiber layer profile measured by optical coherence tomography and its relation to refractive error and axial length. Methods: The Gutenberg Health Study is a population-based study in Mainz, Germany. At the five-year follow-up examination, participants underwent optical coherence tomography, objective refraction and biometry. Peripapillary retinal nerve fiber layer (pRNFL) was segmented using proprietary software. The pRNFL profiles were compared between different refraction groups and the angle between the maxima, i.e., the peaks of pRNFL thickness in the upper and lower hemisphere (angle between the maxima of pRNFL thickness [AMR]) was computed. Multivariable linear regression analysis was carried out to determine associations of pRNFL profile (AMR) including age, sex, optic disc size, and axial length in model 1 and spherical equivalent in model 2. Results: A total of 5387 participants were included. AMR was 145.3° ± 23.4° in right eyes and 151.8° ± 26.7° in left eyes and the pRNFL profile was significant different in the upper hemisphere. The AMR decreased with increasing axial length by −5.86°/mm (95% confidence interval [CI]: [−6.44; −5.29], P < 0.001), female sex (−7.61°; 95% CI: [−8.71; −6.51], P < 0.001) and increased with higher age (0.08°/year; 95% CI: [0.03; 0.14], P = 0.002) and larger optic disc size (2.29°/mm2; 95% CI: [1.18; 3.41], P < 0.001). In phakic eyes, AMR increased with hyperopic refractive error by 2.60°/diopters (dpt) (95% CI: [2.33; 2.88], P < 0.001). Conclusions: The pRNFL profiles are related to individual ocular and systemic parameters. Translational Relevance: Biometric parameters should be considered when pRNFL profiles are interpreted in diagnostics, i.e., in glaucoma

The repositioning of epigenetic probes/inhibitors identifies new anti-schistosomal lead compounds and chemotherapeutic targets

Article Authors Metrics Comments Media Coverage Peer Review Abstract Author summary Introduction Materials and methods Results and discussion Supporting information Acknowledgments References Reader Comments (0) Media Coverage (0) Figures Abstract Background Praziquantel represents the frontline chemotherapy used to treat schistosomiasis, a neglected tropical disease (NTD) caused by infection with macro-parasitic blood fluke schistosomes. While this drug is safe, its inability to kill all schistosome lifecycle stages within the human host often requires repeat treatments. This limitation, amongst others, has led to the search for novel anti-schistosome replacement or combinatorial chemotherapies. Here, we describe a repositioning strategy to assess the anthelmintic activity of epigenetic probes/inhibitors obtained from the Structural Genomics Consortium. Methodology/Principle findings Thirty-seven epigenetic probes/inhibitors targeting histone readers, writers and erasers were initially screened against Schistosoma mansoni schistosomula using the high-throughput Roboworm platform. At 10 μM, 14 of these 37 compounds (38%) negatively affected schistosomula motility and phenotype after 72 hours of continuous co-incubation. Subsequent dose-response titrations against schistosomula and adult worms revealed epigenetic probes targeting one reader (NVS-CECR2-1), one writer (LLY-507 and BAY-598) and one eraser (GSK-J4) to be particularly active. As LLY-507/BAY-598 (SMYD2 histone methyltransferase inhibitors) and GSK-J4 (a JMJD3 histone demethylase inhibitor) regulate an epigenetic process (protein methylation) known to be critical for schistosome development, further characterisation of these compounds/putative targets was performed. RNA interference (RNAi) of one putative LLY-507/BAY-598 S. mansoni target (Smp_000700) in adult worms replicated the compound-mediated motility and egg production defects. Furthermore, H3K36me2, a known product catalysed by SMYD2 activity, was also reduced by LLY-507 (25%), BAY-598 (23%) and siSmp_000700 (15%) treatment of adult worms. Oviposition and packaging of vitelline cells into in vitro laid eggs was also significantly affected by GSK-J4 (putative cell permeable prodrug inhibitor of Smp_034000), but not by the related structural analogue GSK-J1 (cell impermeable inhibitor). Conclusion/Significance Collectively, these results provide further support for the development of next-generation drugs targeting schistosome epigenetic pathway components. In particular, the progression of histone methylation/demethylation modulators presents a tractable strategy for anti-schistosomal control