Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models.

Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692).

Mapping the complexity of task demands during constant observation of patients with complex health behaviors.

Unlicensed patient care assistants (PCAs) are often tasked with providing constant observation (CO) of patients with complex health behaviors. The unique demands of CO are poorly understood, making it challenging to design effective training. Four-component instructional design theory suggests the tasks associated with CO feature non-recurrent challenges, such that effective, simulation-based deliberate practice must reflect real-life variability.

EGFRvIII Confers Sensitivity to Saracatinib in a STAT5-Dependent Manner in Glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with few effective treatments. EGFR alterations, including expression of the truncated variant EGFRvIII, are among the most frequent genomic changes in these tumors. EGFRvIII is known to preferentially signal through STAT5 for oncogenic activation in GBM, yet targeting EGFRvIII has yielded limited clinical success to date.

Rho-kinase inhibition reduces systolic blood pressure and forearm vascular resistance in healthy older adults: a double-blind, randomized, placebo-controlled pilot study.

Rho-kinase has been implicated in the development of hypertension in preclinical studies and may contribute to age-related blood pressure elevation. This study tested the hypothesis that Rho-kinase contributes to elevated systolic blood pressure (SBP) in healthy older adults. Young (18-30 years, 6F/6M) and older (60-80 years, 7F/6M) adults were enrolled in a double-blind, placebo-controlled crossover study using intravenous fasudil infusion to inhibit Rho-kinase.

Ultrasound-based bone tracking using cross-correlation enables dynamic measurements of knee kinematics during clinical assessments.

Purpose: Measuring joint kinematics in the clinic is important for diagnosing injuries, tracking healing and guiding treatments; however, current methods are limited by accuracy and/or feasibility of widespread clinical adoption. Therefore, the purpose of this study was to develop and validate an ultrasound (US)-based method for measuring knee kinematics during clinical assessments.

Methods: We mimicked four clinical laxity assessments (i.