Mass-Action Law Dynamics Theory and Algorithm for Translational and Precision Medicine Informatics

• Main Author: Chou, Ting-Chao
• Format: eBook
• Language: English
• Published: Chantilly Elsevier Science & Technology 2024; Academic Press
• Edition: 1
• Subjects: Medical informatics; Medical innovations; Precision medicine
• ISBN: 9780443288746; 0443288747
• DOI: 10.1016/C2023-0-50888-2

"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 definiti...

Table of Contents:

• 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
• 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