Quantitative systems pharmacology (QSP) is a rapidly emerging discipline with application across a spectrum of challenges facing the pharmaceutical industry, including mechanistically informed prioritization of target pathways and combinations in discovery, target population, and dose expansion decisions early in clinical development, and analyses for regulatory authorities late in clinical development. QSP's development has influences from physiologic modeling, systems biology, physiologically-based pharmacokinetic modeling, and pharmacometrics. Given a varied scientific heritage, a variety of tools to accomplish the demands of model development, application, and model-based analysis of available data have been developed. We report the outcome from a community survey and resulting analysis of how modelers view the impact and growth of QSP, how they utilize existing tools, and capabilities they need improved to further accelerate their impact on drug development. These results serve as a benchmark and roadmap for advancements to the QSP tool set.
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http://dx.doi.org/10.1002/psp4.12373 | DOI Listing |
J Phys Chem B
January 2025
Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United States.
Natural enzymes are powerful catalysts, reducing the apparent activation energy for reactions and enabling chemistry to proceed as much as 10 times faster than the corresponding solution reaction. It has been suggested for some time that, in some cases, quantum tunneling can contribute to this rate enhancement by offering pathways through a barrier inaccessible to activated events. A central question of interest to both physical chemists and biochemists is the extent to which evolution introduces mechanisms below the barrier, or tunneling mechanisms.
View Article and Find Full Text PDFArch Womens Ment Health
January 2025
Department of Psychology, Emory University, Atlanta, GA, USA.
Purpose: Pregnant and postpartum mothers with physical disabilities face discrimination in healthcare settings and high rates of maternal and obstetric complications, as well as having higher rates of lifetime depression prior to pregnancy, potentially increasing their likelihood of experiencing postpartum depression (PPD). Some studies have found higher rates of PPD in mothers with physical disabilities than in mothers without physical disabilities, with more disabling symptoms associated with worse PPD systems; however, the literature is sparse and heterogenous. This systematic review and meta-analysis advanced this area of study by evaluating the strength of the association between PPD and physical disability.
View Article and Find Full Text PDFLasers Med Sci
January 2025
The Department of Preventive Dentistry, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China.
The purpose of this study was to examine how low-energy LED red light influences the early to middle stage of osteogenic differentiation of periodontal ligament stem cells (PDLSCs) via the ERK5 signaling pathway. METHODS: PDLSCs were extracted from periodontal membrane tissue using enzymatic digestion. At three time points of 7, 10, and 14 days after irradiation with 5J/cm LED red light, the expression levels of early to middle-stage osteogenic-related genes ALP, Col-1, BSP, and OPN were detected by real-time fluorescence quantitative PCR(qRT-PCR) in both control and osteogenesis experimental groups.
View Article and Find Full Text PDFMicrobiol Spectr
January 2025
Department of Microbiology, Immunology & Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
a major human fungal pathogen, can form biofilms on a variety of inert and biological surfaces. biofilms allow for immune evasion, are highly resistant to antifungal therapies, and represent a significant complication for a wide variety of immunocompromised patients in clinical settings. While transcriptional regulators and global transcriptional profiles of biofilm formation have been well-characterized, much less is known about translational regulation of this important virulence property.
View Article and Find Full Text PDFNano Lett
January 2025
College of Life Science and Technology, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan 430074, China.
The pursuit of cutting-edge diagnostic systems capable of detecting biomarkers with exceptional sensitivity and precision is crucial for the timely and accurate monitoring of inflammatory responses. In this study, we introduce a dual gold nanoparticle-enhanced metasurface plasmon resonance (Bi-MSPR) biosensor for the ultrasensitive detection of C-reactive protein (CRP). The Bi-MSPR sensor is constructed upon a nanocup array chip with gradient-free electron density, where an innovative metasurface structure is built using a PEI-immobilized dual-gold nanoparticle amplification system.
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