Independent validation of CT radiomics models in colorectal liver metastases:predicting local tumour progression after ablation

Objectives:Independent internal and external validation of three previously published CT-based radiomics models to predict local tumor progression (LTP) after thermal ablation of colorectal liver metastases (CRLM). Materials and methods: Patients with CRLM treated with thermal ablation were collected from two institutions to collect a new independent internal and external validation cohort. Ablation zones (AZ) were delineated on portal venous phase CT 2–8 weeks post-ablation. Radiomics features were extracted from the AZ and a 10 mm peri-ablational rim (PAR) of liver parenchyma around the AZ. Three previously published prediction models (clinical, radiomics, combined) were tested without retraining. LTP was defined as new tumor foci appearing next to the AZ up to 24 months post-ablation. Results: The internal cohort included 39 patients with 68 CRLM and the external cohort 52 patients with 78 CRLM. 34/146 CRLM developed LTP after a median follow-up of 24 months (range 5–139). The median time to LTP was 8 months (range 2–22). The combined clinical-radiomics model yielded a c-statistic of 0.47 (95%CI 0.30–0.64) in the internal cohort and 0.50 (95%CI 0.38–0.62) in the external cohort, compared to 0.78 (95%CI 0.65–0.87) in the previously published original cohort. The radiomics model yielded c-statistics of 0.46 (95%CI 0.29–0.63) and 0.39 (95%CI 0.28–0.52), and the clinical model 0.51 (95%CI 0.34–0.68) and 0.51 (95%CI 0.39–0.63) in the internal and external cohort, respectively. Conclusion: The previously published results for prediction of LTP after thermal ablation of CRLM using clinical and radiomics models were not reproducible in independent internal and external validation. Clinical relevance statement: Local tumour progression after thermal ablation of CRLM cannot yet be predicted with the use of CT radiomics of the ablation zone and peri-ablational rim. These results underline the importance of validation of radiomics results to test for reproducibility in independent cohorts. </p

Wnt signalling and cancer stem cells

[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060

Erratum: Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome (J. Exp. Med. (2020) 217:6 Doi:10.1084/jem.20191804)

The authors regret that in the original version of Table S1, the column for patient 12 was mistakenly duplicated in the column for patient 8. The online Table S1 PDF has been corrected. The error appears only in PDFs downloaded before June 4, 2020

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients’ heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways

Nutrient control of cyanobacterial blooms in the Baltic Sea

Cyanobacterial blooms in the Baltic Sea were investigated with respect to growth Limitation and nitrogen fixation. The community was composed predominantly of Synechococcus spp., and large, heterocystous, nitrogen-fixing cyanobacteria (Aphanizomenon spp, and Nodularia spp.), that usually formed buoyant macroscopic aggregates. Although conspicuous, these aggregates often represented less than 20 to 30% of the total chlorophyll a. Nitrogenase activity was not Limited by molybdate availability, but, instead, by high concentrations of sulfate. This may explain inhibition of nitrogenase activity at high salinities. Inhibition of nitrogenase activity at high salinity did not occur when sulfate concentration was kept low. Nitrogen fixation and growth of the diazotrophic cyanobacteria were limited by iron. Synechococcus spp. was primarily nitrogen Limited but iron appeared to be the secondary limiting substrate, particularly when these organisms depended on nitrate as the source of nitrogen. Nutrient limitation of the picoplanktonic community was particularly apparent when a wind- induced mixing event occurred. These organisms responded by a subsequent doubling of their biomass within 24 h. Mixing of the water column apparently transported nutrients from greater depth into the euphotic zone, causing a temporary relieve of nitrogen limitation. [KEYWORDS: Baltic Sea; cyanobacteria; bloom; picoplankton; nutrients; iron; nitrogen; nitrogen fixation; molybdate; sulfate Nitrogen-fixation; planktonic cyanobacteria;marine-phytoplankton; iron limitation; gas vesicles; cell-size; ocean; eutrophication; synechococcus; communities]