Pharmaceutical applicants conduct (Q)SAR assessments on identified and theoretical impurities to predict their mutagenic potential. Two complementary models-one rule-based and one statistical-based-are used, followed by expert review. (Q)SAR models are continuously updated to improve predictions, with new versions typically released on a yearly basis. Numerous releases of (Q)SAR models will occur during the typical 6-7 years of drug development until new drug registration. Therefore, it is important to understand the impact of model updates on impurity mutagenicity predictions over time. Compounds representative of pharmaceutical impurities were analyzed with three rule- and three statistical-based models covering a 4-8 year period, with the individual time frame being dependent on when the individual models were initially made available. The largest changes in the combined outcome of two complementary models were from positive or equivocal to negative and from negative to equivocal. Importantly, the cumulative change of negative to positive predictions was small in all models (<5%) and was further reduced when complementary models were combined in a consensus fashion. We conclude that model updates of the type evaluated in this manuscript would not necessarily require re-running a (Q)SAR prediction unless there is a specific need. However, original (Q)SAR predictions should be evaluated when finalizing the commercial route of synthesis for marketing authorization.
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http://dx.doi.org/10.1016/j.yrtph.2020.104807 | DOI Listing |
J Nurs Adm
December 2024
Author Affiliations: Research Nurse Scientist (Dr Partridge), Roper St Francis Healthcare; Associate Professor (Dr Jorgenson), College of Nursing, Charleston Southern University; Associate Professor (Dr Johnson), College of Nursing, Medical University of South Carolina; and Director of Nursing Excellence (Dr Lott), Roper St Francis Healthcare, Charleston, South Carolina.
Objective: The purpose of this cross-sectional descriptive study was to examine the relationship of professional governance, resilience, and empowerment among RNs in clinical practice in 1 healthcare system.
Background: Given the emotional and physical demands of nursing, especially in recent years, exploring ways that hope-inducing and resilience-building models can support professional practice is vital to the current and future nursing workforce.
Methods: An anonymous survey consisting of demographic questions, the Adult Hope Scale, Connor-Davidson Resilience Scale, and the Conditions for Work Effectiveness Questionnaire II was offered to 1450 RNs in a nonprofit community-based healthcare system for volunteer participation.
Proc Natl Acad Sci U S A
January 2025
Institute of Science and Technology Austria, AT-3400 Klosterneuburg, Austria.
Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Applied Mathematics Laboratory, Courant Institute of Mathematical Sciences, Department of Mathematics, New York University, New York, NY 10012.
Mechanical systems with moving points of contact-including rolling, sliding, and impacts-are common in engineering applications and everyday experiences. The challenges in analyzing such systems are compounded when an object dynamically explores the complex surface shape of a moving structure, as arises in familiar but poorly understood contexts such as hula hooping. We study this activity as a unique form of mechanical levitation against gravity and identify the conditions required for the stable suspension of an object rolling around a gyrating body.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Research Applications Laboratory, NSF National Center for Atmospheric Research, Boulder, CO 80301.
Precipitation recycling, where evapotranspiration (ET) from the land surface contributes to precipitation within the same region, is a critical component of the water cycle. This process is especially important for the US Corn Belt, where extensive cropland expansions and irrigation activities have significantly transformed the landscape and affected the regional climate. Previous studies investigating precipitation recycling typically relied on analytical models with simplifying assumptions, overlooking the complex interactions between groundwater hydrology and agricultural management.
View Article and Find Full Text PDFJMIR Med Inform
January 2025
Department of Science and Education, Shenzhen Baoan Women's and Children's Hospital, Shenzhen, China.
Background: Large language models (LLMs) have been proposed as valuable tools in medical education and practice. The Chinese National Nursing Licensing Examination (CNNLE) presents unique challenges for LLMs due to its requirement for both deep domain-specific nursing knowledge and the ability to make complex clinical decisions, which differentiates it from more general medical examinations. However, their potential application in the CNNLE remains unexplored.
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