Background: Neuroendocrine carcinomas (NECs) are treated with a frontline platinum-etoposide combination with no standard second-line therapies. We explored a novel combination of nanoliposomal irinotecan (Nal-IRI), 5-fluorouracil (5-FU), and leucovorin (LV) in advanced refractory NECs and investigated the impact of UGT1A1*28 polymorphism on treatment outcomes and toxicity.
Methods: We conducted an open-label, single-arm, multi-center Phase 2 trial in advanced NEC patients of gastroenteropancreatic (GEP) or unknown origin with progression or intolerance to first-line therapy.
Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence of the target protein. To do this, we propose a process to generate naturalistic peptide candidates through Gaussian perturbation of the peptidic latent space of the ESM-2 protein language model and subsequently screen these novel sequences for target-selective interaction activity via a contrastive language-image pretraining (CLIP)-based contrastive learning architecture.
View Article and Find Full Text PDFBackground And Objective: Vildagliptin sustained release (XR), a formulation that provides vildagliptin 100 mg with a once-daily dose administration, is a recent introduction to manage type 2 diabetes mellitus in India. This study aimed to evaluate the effectiveness and tolerability of vildagliptin XR in patients with type 2 diabetes in real-world clinical settings.
Methods: This was an observational, prospective, multicenter, cohort study conducted in India, which included patients with type 2 diabetes uncontrolled on metformin XR monotherapy with glycated hemoglobin (HbA1c) > 7.
Background: Gratitude interventions are used to cultivate a sense of gratitude for life and others. There have been mixed results of the efficacy of gratitude interventions' effect on psychological well-being with a variety of populations and methodologies.
Objectives: The objective of our study was to test the effectiveness of a gratitude intervention smartphone app on university students' psychological well-being.
The electrification of the transport sector is crucial for reducing greenhouse gas emissions and the reliance on fossil fuels. Battery electric vehicles (BEVs) depend on critical materials (CMs) for their batteries and electronic components, yet their widespread adoption may face constraints due to the limited availability of CMs. This study assesses the implications of vehicle electrification and lightweighting (material substitution) on the U.
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