A robust optimization model for intensity-modulated radiotherapy: Cheap-Minimax.

Background: Over the past three decades, the intensity-modulated radiotherapy (IMRT) has become a standard technique, enabling highly conformal dose distributions tailored to specific clinical objectives. Despite these advancements, IMRT treatment plans are significantly susceptible to uncertainties during both the planning and delivery phases. The most commonly used strategy to address these uncertainties is the margin-based or planning target volume (PTV) approach, which relies on the so-called dose cloud approximation.

Human induced pluripotent stem cell-derived myotubes to model inclusion body myositis.

Inclusion body myositis (IBM) is an inflammatory myopathy that displays proximal and distal muscle weakness. At the histopathological level, the muscles of IBM patients show inflammatory infiltrates, rimmed vacuoles and mitochondrial changes. The etiology of IBM remains unknown, and there is a lack of validated disease models, biomarkers and effective treatments.

Generation of an inducible dCas9-SAM human PSC line for endogenous gene activation.

The CRISPR/Cas9 system has transformed genome editing by enabling precise modifications for diverse applications. Recent advancements, including base editing and prime editing, have expanded its utility beyond conventional gene knock-out and knock-in strategies. Additionally, several catalytically dead Cas9 (dCas9) proteins fused to distinct activation domains have been developed to modulate endogenous gene expression when directed to their regulatory regions by specific single-guide RNAs.

CD151 identifies an NK cell subset that is enriched in COVID-19 patients and correlates with disease severity.

Severe coronavirus disease 2019 (COVID-19) often leads to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease.

Therapeutic modulation of KIT ligand in melanocytic disorders with implications for mast cell diseases.

KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and activation. Blockade of this pathway results in cell depletion, while overactivation leads to mastocytosis or melanoma. Expression defects are associated with pigmentary and mast cell disorders.