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Mass-action law dynamics theory and algorithm for translational and precision medicine informatics /

Provides a comprehensive overview and update of the mass-action law-based unified dose-effect biodynamics, pharmacodynamics, bioinformatics, and the combination index theorem for synergy definition (MAL-BD/PD/BI/CI). Contents advocate the fundamental MAL-PD/BI/CI/BI principle for biomedical R&D,...

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Bibliographic Details
Main Author: Chou, Ting-Chao (Author)
Corporate Author: ScienceDirect (Online service)
Format: eBook
Language:English
Published: London ; San Diego, CA : Academic Press, an imprint of Elsevier, [2024]
Edition:First edition.
Subjects:
Medical informatics.
Clinical trials > Data processing.
Medical Informatics
Médecine > Informatique.
Études cliniques > Informatique.
Electronic books.
Online Access:Connect to the full text of this electronic book
Table of Contents:
  • Intro
  • Mass-Action Law Dynamics Theory and Algorithm for Translational and Precision Medicine Informatics
  • Copyright
  • Contents
  • Preface
  • Abbreviations
  • Acknowledgments
  • Chapter I: A new alternative concept for cost-effective R&amp
  • D: The MAL-dynamics/algorithms/digital informatics
  • A. Challenges from complexity and diversity and the MAL-solutions
  • B. A complementary alternative new approach to the traditional approach for biomedical R&amp
  • D, drug evaluations, and beyond
  • 1. The median-effect equation is the unified general equation of MAL dynamics of action
  • 2. The combination index equation (CIE) is the unified general principle of interactions
  • 3. The dose-reduction index (DRI) is an indication of reducing toxicity by drug combination synergism
  • 4. The polygonogram is a diagram depicting three or more drug interactions for cocktail design
  • The general unified theory is based on the mass-action law for single drugs and drug combinations
  • The algorithm for drug or entity interaction simulation
  • C. MAL applicability and implementations
  • 1. MAL theory/algorithm-based approach vs observation/statistics-based approach
  • 2. The unified MAL-PD principle integration and its general applications
  • 3. MAL three unified general equations: MEE, CIE, and DRIE work together
  • 4. Usefulness and limitations of MAL-PD versus PK
  • Range of applicability
  • Dose-dependency and end-point of measurement
  • D. The PK/PD issues
  • 1. Prerequisites for MAL-PD studies and clinical trials
  • 2. Comparison of PD and PK: Why they are basically different principles
  • References
  • Chapter II: General dynamics principle for experimental design of all dose-effect analysis and computer simulation
  • A. The principle and process for drug evaluation: Dose and effect analysis
  • 1. FDA drug evaluation: Basic roles at OCP/OTS/CDER.
  • 2. Issues of major concern
  • 3. PD principle and the exact definitions of ``PD´´ and ``Synergism´´
  • B. Two different anti-HIV clinical trials: Protocol design and data analysis
  • 1. Clinical trials of AZT + IFN combinations
  • 2. Protocol design and results: AZT + IFN clinical trials
  • 3. MAL-PD/CI-based design protocol and analysis
  • C. Clinical trials of AZT+3TC based on the traditional statistical approach
  • 1. Protocol design for AZT, 3-TC, and their combinations (AZT+3TC) in clinical trials
  • 2. The results and conclusions for AZT + 3TC clinical trials
  • D. Comparisons of two clinical trials: AZT + 3TC vs AZT + IFN
  • E. Efficiency, cost-effectiveness, and integrative computerized automation
  • F. Preclinical and clinical trials: Definitions of ``additive effect,´´ ``synergism,´´ and ``antagonism´´
  • References
  • Chapter III: MAL-PD/CI approach for biomedical R&amp
  • D in vitro and in animals
  • A. Sample size, efficiency, and cost-effectiveness
  • B. Significance of the MAL-PD approach
  • 1. Reliability and accuracy of measurement
  • 2. Avoid the extreme numbers and unreliable results
  • 3. Selection of the end-point for measurement
  • C. Illustration of drug combination in vitro using MAL-PD/CI method
  • D. Illustration of drug combination in animals using MAL-PD/CI method
  • E. Application of MAL-PD/CI method in organ transplantation studies
  • References
  • Chapter IV: Implementation of MAL-PD for Econo-Green R&amp
  • D
  • A. Availability of computer software for automated MAL-PD/CI/BI
  • B. Comparisons and ranking of candidate drugs and biosimilars in vitro and in vivo using the same MAL-PD principle
  • C. Standardized drug evaluations for single drugs using the median-effect principle of MAL-PD
  • References
  • Chapter V: Digital R&amp.
  • D approach to international FDA drug evaluation, clinical pharmacology, and clinical trial guidance
  • A. The observatory statistical PK principle plays an important role in FDA policy and priority
  • B. Modernization of drug evaluation guidance and guidelines
  • C. Why FDA drug evaluation is so relevant to a pharmacologist
  • D. New avenues for integrated and streamlined drug evaluation
  • E. The international FDA guidance and drug evaluation guidelines need an update and modernization
  • F. The current uncertainty, ambiguity, and confusion in drug R&amp
  • D and regulations
  • References
  • Chapter VI: The epothilone story: Experimental success and clinical failure
  • A. A pharmacologist and theoretical biologist for life
  • B. Epothilones: The interaction between chemists and pharmacologists
  • C. Anticancer epothilone preclinical studies as examples
  • D. Major MAL-PD findings of epothilones
  • E. A clinical trial study of isofludelone (KOS-1803)
  • F. A review of the failure of the isofludelone [KOS-1803] clinical trial
  • References
  • Chapter VII: MAL-PD advocacy: Public hearing, public comments and scientific recommendations
  • A. Public meetings and public hearings at US FDA
  • B. Public comments to FDA
  • C. Presentation on MAL-PD theory and applications at CPIM, OTS, FDA
  • D. The problem of undefinable vague ``models´´
  • E. Consolidation and definition of precision medicine, translational medicine, and digital biology
  • References
  • Chapter VIII: Consensus for international FDAs on definitions of ``MAL-PD´´ and ``Synergism´´
  • A. The role of drug evaluation from international FDAs on drug evaluation
  • B. The International Council for Harmonization on ``PD´´ and ``synergism´´ for R&amp
  • D
  • C. Different thinking for the clinical trial protocol design and data analysis/simulation
  • References.
  • Chapter IX: Historical, philosophical, and mathematical analysis: Why the MAL-PD approach and the traditional approach ar ...
  • A. The MAL theory-based ``top-down´´ versus the experimental observation-based ``bottom-up´´ for bio-R&amp
  • D and clinical trials
  • B. The inspiration and support from the visionary giants
  • C. Nature's equilibrium ecosystem and interdisciplinary common basic principle from ancient to modern
  • D. Artificial intelligence, cloud computing, computer learning, open AI, generative AI, and ChatGPT are the bottom-up pla ...
  • 1. The mighty AI for speed, volume, accuracy, and Inference
  • 2. Evidence of limitations of AI usefulness and risk
  • E. Conversation with ChatGPT: Statements, informatics, errors, and this author's comments
  • 1. The Conversations between a bio-medical scientist and ChatGPT on MAL-PD: T.C. Chou's comments and corrections
  • 2. The Conversations between a librarian and ChatGPT on MAL-PD: T.C. Chou's comments and corrections
  • 3. Chou's general comments on the ChatGPT answers
  • F. System, pattern, combinatorial, number theory, and new frontiers for further mathematical developments: The contractio ...
  • 1. Nature's mass-action law as the model
  • 2. Patterns and mechanistic randomness in linear and circular input and output events of enzyme reactions
  • l-Asparagine biosynthesis (Chou Ph.D. thesis 1970, Yale University)
  • 3. Nature's MAL new revelations
  • A mathematical approach to deducing kinetic mechanisms (see Appendix VI for more details)
  • For the linear enzyme reaction sequences in the linear system
  • For the circular enzyme mechanism system
  • Pattern analysis of enzyme reaction system
  • 4. MAL bio-model leads to the Second-Degree Pascal Triangle
  • A mathematical new triangle derived from a biochemical input and output model
  • Pattern and combinatorial analysis.
  • G. The author rank-weighted triangle and algorithm for citation attribution in n-authored papers
  • 1. Assumptions and definitions
  • 2. The authorship-rank weighted triangle and algorithm
  • 3. The approach of combinatory-pattern and system analysis in research
  • 4. The derivation of the general attribution equation for n-authored papers
  • 5. The general algorithm for computerized simulation
  • 6. Discussions and recommendations for multiple-authored papers
  • 7. The Broadness of applicability of a single paper
  • H. The perspectives of the MAL-BP/PD/CI informatics
  • References
  • Chapter X: Multidisciplinary examples of applications: Papers using the MAL-PD/BD/CI/BI theory/method
  • A. Applications MAL-PD and CI in cancer-related research
  • 1. Anticancer and antiviral agents
  • B. Applications in antimicrobial research
  • C. Applications in basic biomedical sciences (2020-23)
  • D. MAL-PD theory/method of applications in different disciplines
  • E. Applications in immunology and organ transplantation
  • F. Philosophical propositions, AI, conceptual discussions and theoretical biology
  • G. Early theoretical, physical, biophysical, biochemical, and elementary particle studies
  • H. Other theories and concepts of non-MAL-PD approach, computer learning and artificial intelligence
  • References
  • Chapter XI: Concluding remarks
  • References
  • Postscript
  • Summary
  • Appendix I
  • Appendix II
  • Appendix III
  • Appendix IV
  • Appendix V
  • Appendix VI
  • Glossary and definitions
  • References
  • Research supports
  • Research supports
  • Conflict of interest
  • Disclaimer/Publishers note
  • Declarations
  • Index.