A5100766514- Lipid Membrane Structure and Behavior
- RNA modifications and cancer
- RNA Research and Splicing
- Biosimilars and Bioanalytical Methods
- Muscle Physiology and Disorders
- Chronic Lymphocytic Leukemia Research
- RNA and protein synthesis mechanisms
- Antimicrobial Peptides and Activities
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Protein Structure and Dynamics
- Statistical Methods in Clinical Trials
- Urinary and Genital Oncology Studies
- Mitochondrial Function and Pathology
- Spectroscopy and Quantum Chemical Studies
- Lipid metabolism and biosynthesis
- Protein Interaction Studies and Fluorescence Analysis
- Bladder and Urothelial Cancer Treatments
- Cancer Treatment and Pharmacology
- Heme Oxygenase-1 and Carbon Monoxide
- Nanoparticle-Based Drug Delivery
- Sphingolipid Metabolism and Signaling
- Hemoglobin structure and function
- RNA regulation and disease
- Liver Disease and Transplantation
Simulations Plus (United States)
2020-2023
Yale University
2022-2023
Cognizant (United States)
2021
St Vincent's Hospital
2020
The University of Melbourne
2020
Nationwide Children's Hospital
2013-2019
York University
2010
Rice University
1995-2008
OBJECTIVES: The objective of this analysis is to demonstrate a general simulation-based methodology assess sample size and power for clinical studies with exposure metric based end points. _x000D_ METHODS: A two-compartment model following intravenous administration moderate between subject variability on pharmacokinetic parameters was used (PK) simulations. An example drug development scenario infusion time change from 1-hour 0.5-hour used. PK profiles reference test populations were...
Abstract Purpose This analysis evaluated the relationship between concentrations of quizartinib and its active metabolite AC886 QT interval corrected using Fridericia’s formula (QTcF) in patients with relapsed/refractory acute myeloid leukemia (AML) treated phase 3 QuANTUM-R study (NCT02039726). Methods The dataset included 226 AML. Quizartinib dihydrochloride was administered as daily doses 20, 30, 60 mg. Nonlinear mixed-effects modeling performed observed time-matched mean...
The main components of the essential cellular process eukaryotic ribosome biogenesis are highly conserved from yeast to humans. Among these, U3 Associated Proteins (UTPs) a small subunit processome subcomplex that coordinate first two steps in transcription and pre-18S processing. While we have identified human counterparts most Utps, homologs Utp9 Bud21 (Utp16) remained elusive. In this study, find NOL7 is likely ortholog Bud21. Previously described as tumour suppressor through regulation...
Abstract Background: In the IMvigor130 primary analysis in patients (pts) with untreated locally advanced or mUC, a trend toward favorable OS atezo (anti-PD-L1) monotherapy (Arm B) vs placebo + platinum/gemcitabine (plt/gem; Arm C) was seen pts PD-L1-expressing immune cells on ≥5% of tumor area (IC2/3 per VENTANA SP142 IHC assay; Galsky Lancet 2020). We report clinical outcomes B C from second interim analysis, including efficacy cisplatin-ineligible pts. Methods: Pts were randomized 1:1:1...
Background and aims Prison-based HCV treatment rates remain low due to multiple barriers, including accessing transient elastography for cirrhosis determination. The AST-to-platelet ratio index (APRI) FIB-4 scores have excellent negative predictive value (NPV) in hospital cohorts exclude cirrhosis. We investigated their performance a large cohort of prisoners with infection. Methods This was retrospective study participants assessed by prison-based hepatitis program. sensitivity,...
Abstract Quizartinib is an FMS‐like tyrosine kinase 3 (FLT3) inhibitor that has shown robust clinical activity in patients with FLT3‐ internal tandem duplication–mutated relapsed/refractory acute myeloid leukemia (AML). This analysis evaluated the population pharmacokinetics (PK) of quizartinib and its active metabolite, AC886, a pooled data from 649 healthy volunteers or AML 8 trials including phase QuANTUM‐R study. was given as single dose multiple once‐daily doses 20, 30, 60, 90 mg....
How antimicrobial peptides form pores in membranes is of interest as a fundamental membrane process. However, the underlying molecular mechanism, which has potential applications therapeutics, nonviral gene transfer, and drug delivery, been dispute. We have resolved this mechanism by observing time-dependent process pore formation individual giant unilamellar vesicles (GUVs) exposed to melittin solution. An GUV first expanded its surface area at constant volume then suddenly reversed...
Background and Hypothesis:Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with undefined etiology the fifth leading cause of death worldwide. AD pathology characterized by amyloid-beta (Aβ) plaques. Previous work demonstrated that alterations in microvasculature are some earliest recognizable changes AD, most patients dementia have mixed vascular pathologies. We investigated functional impacts metabolic associated immune-vascular perturbation on underlying mechanisms...
Sphingosine-1-phosphate (S1P) binding to the S1P-1 receptor (S1P1R) controls egress of lymphocytes from lymphoid organs and targets modulation immune responses in autoimmune diseases. Pharmacologic S1P receptors has been linked heart rate reduction. BMS-986166, a prodrug active phosphorylated metabolite BMS-986166-P, presents an improved cardiac safety profile preclinical studies compared other S1P1R modulators. The pharmacokinetics, safety, pharmacodynamics BMS-986166 versus placebo after...
Currently, exon skipping therapies for Duchenne muscular dystrophy (DMD) have been developed patients with out-of-frame deletions where treatment will lead translation of an internally truncated but partially functional dystrophin protein. In contrast, we are focusing on treating duplications mutations, accounting around 6% all resulting in wild-type transcript and a full-length Modeling the most common single duplication first mouse containing duplicated 2. We performed proof-of-principle...
Bicuspid aortic valve (BAV) is the most common type of cardiac malformation with an estimated prevalence 1-2% in population. BAV results significant morbidity as it one leading causes stenosis and regurgitation adults. We previously reported that mutations signaling transcriptional regulator, NOTCH1 , were a cause non-syndromic autosomal-dominant human pedigrees. The Notch pathway critical for multiple cell differentiation processes, Notch1 expressed developing adult valve. Recently, we have...
Abstract The main components of the essential cellular process eukaryotic ribosome biogenesis are highly conserved from yeast to humans. Among these, transcription-U3 Associated Proteins (t-UTPs) a small subunit processome subcomplex that coordinate first two steps in transcription and pre-18S processing. While we have identified human counterparts most Utps, homologs Utp9 Bud21 (Utp16) remained elusive. In this study, find NOL7 is likely ortholog Bud21. Previously described as tumor...
e21087 Background: MYL-1402O (MYL) is a proposed biosimilar to bevacizumab reference product. A multicenter, double blind randomized, phase 3 study compared the efficacy, safety, PK, and immunogenicity of MYL Avastin in patients with Stage IV metastatic nsNSCLC. Patients received either or product, combination carboplatin-paclitaxel up 18 weeks (6 cycles) followed by monotherapy for an additional 24 (8 cycles). The objective was develop Pop PK model based on data from pooled single dose...