Real-world characteristics and outcomes of patients with multiple myeloma receiving second-line treatment in England.

Introduction: Despite recent advances in first-line therapies for multiple myeloma (MM), most patients relapse or become refractory, underscoring the need for effective second-line (2L) regimens for relapsed/refractory MM (RRMM).

Methods: This study describes the real-world baseline characteristics, treatment patterns and clinical outcomes of adult patients diagnosed with MM between 2013 and 2020 using data collated by the National Cancer Registration and Analysis Service (NCRAS) of the National Health Service in England. The study cohorts were broadly aligned to the eligibility criteria of the ongoing DREAMM-7 (D7) and DREAMM-8 (D8) clinical trials.

mTOR signaling regulates multiple metabolic pathways in human lung fibroblasts after TGF-β and in pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a fatal disease characterized by the transforming growth factor (TGF-β)-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive replacement of healthy lungs with scar tissue. We and others have shown that TGF-β-mediated activation of the mechanistic target of rapamycin complex 1 (mTORC1) and downstream upregulation of activating transcription factor 4 (ATF4) promotes metabolic reprogramming in lung fibroblasts characterized by upregulation of the de novo synthesis of glycine, the most abundant amino acid found in collagen protein. Whether mTOR and ATF4 regulate other metabolic pathways in lung fibroblasts has not been explored.

Bound-State Beta Decay of ^{205}Tl^{81+} Ions and the LOREX Project.

Stable ^{205}Tl ions have the lowest known energy threshold for capturing electron neutrinos (ν_{e}) of E_{ν_{e}}≥50.6  keV. The Lorandite Experiment (LOREX), proposed in the 1980s, aims at obtaining the longtime averaged solar neutrino flux by utilizing natural deposits of Tl-bearing lorandite ores.

Role of Arginine and its Metabolism in TGF-β-Induced Activation of Lung Fibroblasts.

Arginine is a conditionally essential amino acid with known roles in protein production, nitric oxide synthesis, biosynthesis of proline and polyamines, and regulation of intracellular signaling pathways. Arginine biosynthesis and catabolism have been linked to TGF-β-induced activation of fibroblasts in the context of pulmonary fibrosis; however, a thorough study on the metabolic and signaling roles of arginine in the process of fibroblast activation has not been conducted. Here, we used metabolic dropouts and labeling strategies to determine how activated fibroblasts utilize arginine.

Sustained hypoxia but not intermittent hypoxia induces HIF-1α transcriptional response in human aortic endothelial cells.

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxic environments at the cellular level and is an independent risk factor for the development of cardiovascular disease. Endothelial cell (EC) dysfunction precedes the development of cardiovascular disease; however, the mechanisms by which ECs respond to these intermittent hypoxic events are poorly understood. To better understand EC responses to hypoxia, we examined the effects of sustained hypoxia (SH) and intermittent hypoxia (IH) on the activation of HIF-1α in ECs.