Anticancer and therapeutic efficacy of XPO1 inhibition in pancreatic ductal adenocarcinoma through DNA damage and modulation of miR-193b/KRAS/LAMC2/ERK/AKT signaling cascade.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and grave malignancies with confined and ineffective therapeutic options. XPO1 is a critical regulator of nuclear export and activation of tumor suppressor proteins. The present study evaluated the therapeutic potential and molecular mechanisms of XPO1 inhibition against PDAC.

Analysis of Multiple Print-Head Displacement Mechanisms in 3D Space for Material Extrusion Machine.

For wider adoption of the material extrusion (MatEx)-based additive manufacturing (AM) process, it is important to understand the systems for an improved production rate of the machine. This AM process is the most adaptable and popular due to its wide availability, scalability, compatibility with a broad range of thermoplastic materials, and decreasing cost of personal MatEx-based systems. The performance limits are being explored by many researchers, but none have tried to find the efficacy of different kinematic configurations.

Population modelling of nilotinib exposure vs. longitudinal BCR::ABL1 response in patients with chronic phase chronic myeloid leukaemia using a semimechanistic disease model.

Aims: This study aims to evaluate the exposure-efficacy relationship of nilotinib and longitudinal BCR::ABL1 levels in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase (CML-CP) and those who are imatinib-resistant or intolerant using a semimechanistic disease model.

Methods: The analysis included 489 CML-CP patients from 3 nilotinib trials (NCT00109707; NCT00471497; NCT01043874) with duration of follow-up ranging from 2 to 9 years. The semimechanistic disease model of CML-CP consisted of quiescent leukaemic stem cells, proliferating drug-susceptible and -resistant bone marrow cells.

Genetic and allelic heterogeneity in 248 Indians with skeletal dysplasia.

Skeletal dysplasias are a clinically and genetically heterogeneous group of rare disorders. Studies from large cohorts are essential to provide insights into the disease epidemiology, phenotypic spectrum, and mutational profiles. Here we enumerate additional 248 Indians from 197 families with a skeletal dysplasia, following a similar study earlier.