ASCL1 is a neuroendocrine lineage-specific oncogenic driver of small cell lung cancer (SCLC), highly expressed in a significant fraction of tumors. However, ∼25% of human SCLC are ASCL1-low and associated with low neuroendocrine fate and high MYC expression. Using genetically engineered mouse models (GEMMs), we show that alterations in Rb1/Trp53/Myc in the mouse lung induce an ASCL1^(+) state of SCLC in multiple cells of origin. Genetic depletion of ASCL1 in MYC-driven SCLC dramatically inhibits...
Fri, May 21, 2021
Anti-TNF therapeutics bind and sequester tumor necrosis factor (TNF) to prevent downstream signaling and are clinically important in the treatment of several autoimmune diseases. Effective treatment with these drugs requires frequent therapeutic drug monitoring (TDM). Current analytical methods, including reporter gene assay (RGA), enzyme-linked immunosorbent assay (ELISA), and mobility shift assay (MSA), can be technically rigorous, slow, and expensive. These qualities prevent the...
Wed, May 19, 2021
CONCLUSION: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC in order to lay the foundation for developing new therapies and improve outcomes in this challenging population.
Wed, May 19, 2021
CONCLUSIONS: Viral bloodstream detections were common in children presenting to the ED with suspected systemic infections. Although overall frequencies of SBIs among subjects with and without viral bloodstream detections did not differ significantly, combining whole blood viral testing with urinalysis provided high NPV for excluding SBI.
Wed, May 19, 2021
The impact of COVID-19 has been largely described after symptom development. Although the SARS-CoV-2 virus elevates heart rate (HR) prior to symptom onset, whether this virus evokes other presymptomatic alterations is unknown. This Case Study details the presymptomatic impact of COVID-19 on vascular and skeletal muscle function in a young woman (24yrs, 173.5cm, 89kg, BMI: 29.6kg·m^(-2)). Vascular and skeletal muscle function were assessed as part of a separate study with the first and second...
Tue, May 18, 2021
OBJECTIVE: Dravet syndrome (DS) is a rare but catastrophic genetic epilepsy, with 80% of patients carrying a mutation in the SCN1A gene. Currently, no antiseizure drug (ASD) exists that adequately controls seizures. In the clinic, individuals with DS often present first with a febrile seizure and, subsequently, generalized tonic-clonic seizures that can continue throughout life. To facilitate the development of ASDs for DS, the contract site of the National Institute of Neurological Disorders...
Tue, May 18, 2021
No abstract
Tue, May 18, 2021
CONCLUSION: The implemented semi-automatic segmentation procedure improved data analysis efficiency. Quantitative methods using contrast-enhanced MRI with histological validation are sensitive for detection of blood-spinal cord barrier opening induced by magnetic resonance-guided focused ultrasound.
Mon, May 17, 2021
Despite excellent cure rates in newly diagnosed patients with B-cell acute lymphoblastic leukemia (B-ALL), therapies that improve outcomes for children with relapsed or refractory (r/r) B-ALL are needed. Chimeric antigen receptor (CAR)-T cell therapy has demonstrated durable responses and a manageable safety profile in children, adolescents, and young adults less than 26 years old with r/r B-ALL, including patients who have relapsed after allogeneic stem cell transplant. This comprehensive...
Mon, May 17, 2021
CONCLUSIONS: Implementation of a threshold compliance tool was associated with a marked and significant reduction in out-of-range ICP values. Benefit was, however, not evident in a randomized controlled trial. Our analysis provides a unique perspective on our failure to detect an apparent true difference and may provide insights into other neurotrauma trial failures.
Sun, May 16, 2021
