Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins that regulate postprandial glucose regulation, stimulating insulin secretion from pancreatic β-cells in response to food ingestion. Modified GLP-1 receptor agonists (GLP-1RAs) are being administered for the treatment of obesity and type 2 diabetes mellitus (T2DM). Strongly related to those disorders, metabolic dysfunction-associated steatotic liver disease (MASLD), especially its aggressive form, defined as metabolic dysfunction-associated steatohepatitis (MASH), is a major healthcare burden associated with high morbidity and extrahepatic complications. GLP-1RAs have been explored in MASH patients with evident improvement in liver dysfunction enzymes, glycemic control, and weight loss. Importantly, the combination of GLP-1RAs with GIP and/or glucagon RAs may be even more effective via synergistic mechanisms in amelioration of metabolic, biochemical, and histological parameters of MASLD but also has a beneficial impact on MASLD-related complications. In this current review, we aim to provide an overview of incretins’ physiology, action, and signaling. Furthermore, we provide insight into the key pathophysiological mechanisms through which they impact MASLD aspects, as well as we analyze clinical data from human interventional studies. Finally, we discuss the current challenges and future perspectives pertinent to this growing area of research and clinical medicine.

Immune checkpoint inhibitors (ICIs) have been approved to treat a variety of malignancies, including melanoma, improving the prognosis of these patients. However, they also cause a wide spectrum of rare immune-related adverse events (irAEs), not well-described yet. Although many endocrinopathies have been recognized as irAEs, primary hypoparathyroidism has rarely been reported, and thus clinical suspicion remains low. Herein, we describe the case of a 68-year-old female patient with metastatic melanoma who was admitted to the emergency department with acute symptomatic hypocalcemia due to immune-related (ir)-hypoparathyroidism after 2 cycles of nivolumab/ipilimumab. The patient was treated symptomatically, and her calcium levels were normalized. Parathyroid hormone levels were partially restored during the 6 months of follow-up. A literature review was conducted, summarizing all other subjects who developed ir-hypoparathyroidism after exposure to ICI-based regimen. The review identified 10 additional cases of hypoparathyroidism during immunotherapy. Interestingly, all melanoma cases with ir-hypoparathyroidism had received nivolumab/ipilimumab; 3 of them were also screened and detected with positive calcium-sensing receptor (CaSR) antibodies. Primary hypoparathyroidism may acutely manifest with symptomatic hypocalcemia and care providers should be aware of this rare irAE.

In the context of SPARQL, queries could be seen as patterns that are matched against an RDF graph. Until recently, it was not possible to create a pattern without specifying the exact path of the underlying graph (in terms of real data and/or variables) that would match against the graph. The advent of SPARQL 1.1 introduced property paths as a new graph matching paradigm that allows the employment of Kleene star * (and it's variant +) unary operators to build SPARQL queries that are agnostic of the underlying RDF graph structure. In this paper, we propose a generic SPARQL rewriting method that facilitates the execution of property path queries employing Kleene star * (and it's variant +) unary operators. This method is further extended through the employment of the RDF-Type Summary graph in an effort to reduce query execution time. The proposed approach is accordingly evaluated in terms of scalability with promising results.