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Introduction Biallelic PDX1 variants are a rare cause of isolated pancreatic agenesis and neonatal diabetes (NDM) without exocrine pancreatic insufficiency, with 17 cases reported in the literature.Research design and methods To determine the phenotypic variability caused by this rare genetic aetiology, we investigated 19 individuals with NDM resulting from biallelic disease-causing PDX1 variants.Results Of the 19 individuals, 8 (42%) were confirmed to have exocrine insufficiency requiring replacement therapy. Twelve individuals (63.2%) had extrapancreatic features, including 8 (42%) with conditions affecting the duodenum and/or hepatobiliary tract. Defects in duodenum development are consistent with previous Pdx1 ablation studies in mice which showed abnormal rostral duodenum development.Conclusions Our findings show that recessive PDX1 variants can cause a syndromic form of NDM, highlighting the need for clinical assessment of extrapancreatic features in individuals with NDM caused by PDX1 variants.

During epithelial-mesenchymal transition (EMT) in cancer progression, tumor cells switch cadherin profile from E-cadherin to cadherin-11 (CDH11), which is accompanied by increased invasiveness and metastatic activity. However, the mechanism through which CDH11 may affect tumor growth and metastasis remains elusive. Here, we report that CDH11 was highly expressed in multiple human tumors and was localized on the membrane, in the cytoplasm and, surprisingly, also in the nucleus. Interestingly, β-catenin remained bound to carboxy-terminal fragments (CTFs) of CDH11, the products of CDH11 cleavage, and co-localized with CTFs in the nucleus in the majority of breast cancer samples. Binding of β-catenin to CTFs preserved β-catenin activity, whereas inhibiting CDH11 cleavage led to β-catenin phosphorylation and diminished Wnt signaling, similar to CDH11 knockout. Our data elucidate a previously unknown role of CDH11, which serves to stabilize β-catenin in the cytoplasm and facilitates its translocation to the nucleus, resulting in activation of Wnt signaling, with subsequent increased proliferation, migration and invasion potential., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Reddit, the fifth most popular website in the United States, boasts a large and engaged user base on its dermatology forums where users crowdsource free medical opinions. Unfortunately, much of the advice provided is unvalidated and could lead to the provision of inappropriate care. Initial testing has revealed that artificially intelligent bots can detect misinformation regarding tanning and essential oils on Reddit dermatology forums and may be able to produce responses to posts containing misinformation., Objective: To analyze the ability of bots to find and respond to tanning and essential oil-related health misinformation on Reddit's dermatology forums in a controlled test environment., Methods: Using natural language processing techniques, we trained bots to target misinformation, using relevant keywords and to post prefabricated responses. By evaluating different model architectures across a held-out test set, we compared performances., Results: Our models yielded data test accuracies ranging 95%-100%, with a Bidirectional Encoder Representations from Transformers (BERT) fine-tuned model resulting in the highest level of test accuracy. Bots were then able to post corrective prefabricated responses to misinformation in a test environment., Conclusions: Using a limited data set, bots accurately detected examples of health misinformation within Reddit dermatology forums. Given that these bots can then post prefabricated responses, this technique may allow for interception of misinformation. Providing correct information does not mean that users will be receptive or find such interventions persuasive. Further studies should investigate this strategy's effectiveness to inform future deployment of bots as a technique in combating health misinformation., (©Monique A Sager, Aditya M Kashyap, Mila Tamminga, Sadhana Ravoori, Christopher Callison-Burch, Jules B Lipoff. Originally published in JMIR Dermatology (http://derma.jmir.org), 30.09.2021.)