Nomination for 2018 Yidan Prize, recognition in the field of MEDICAL education: development of curation methodologies for scientific content – 2018 Nominee, Aviva Lev-Ari, PhD, RN
March 31, 2018
Yidan Prize for Education Development recognizes innovative ideas that tackle pressing challenges in the field of education.
Nomination for recognition as means in tackling challenges in the field of MEDICAL education, the
“Sixteen Volumes in Medicine and Life Sciences” in the LPBI Group’s BioMed e-Series, an initiative of innovative ideas and development of curation methodologies for scientific content.
Yidan Prize 2018 Nominee Aviva Lev-Ari
(Form ID : D181569) www.yidanprize.org
Judging Criteria
1. Sustainability
The books are online topics in medical science, diagnostics and therapy that are maintained by updating the chapter material in the Biomed e-series directly pertaining to the chapter content that is directly available from the e-series online. The Chapters are compiled from detailed review of the available literature, and the content of each book is related to current concepts researched and coordinated for the published work. One of the Research Categories: Interviews with Scientific Leaders includes in its growth plan the option of Podcasts which is an Audio Media component to supplement the video media component which is used extensively in the BioMed e-Series
How we accomplish the Sustainability goal:
- Online continuing updates are made to articles in the Journal
- Each e-Book has an abbreviated electronic Table of Contents which consists of LIVE LINKS for each article in an e-Book to the article in the Journal. eReaders of the e-Books clicks on the link and get the most updated State of Science for each topic in the e-books.
- Journal Ontology is a relational and hierarchical knowledge base allowing for expansion of the content creation process on these two dimensions and is not limited to these two. For example: One of the Research Categories: Interviews with Scientific Leaders includes in its growth plan the option of Podcasts which is an Audio Media component to supplement the video media component which is used extensively in the BioMed e-Series.
2. A Future-Oriented Vision
Cutting edge research is the content of a research reservoir that allows for the creation of up-to-date content, and which supports new developments as they arise. The cutting edge concepts are reviewed in concordance with timely conferences on topical material. These conferences are also recorded and conveyed in the related documents. Since 2013, International leading Breakthroughs in BioTechnology Conferences are covered in Real Time by Dr. Aviva Lev-Ari on PRESS Pass.
How we accomplish the Future-Oriented Vision goal:
- The Intellectual Property Vault (N= +5,200) has the potential of being used for creation of New Titles for New e-Books. It is a reservoir of Ideas in the form of Research Categories populated by Scientific Curations
- Online reach is growing and is driven by cutting edge subject matters added on a continuous basis to the Intellectual Property Vault
- Innovations in Drug Discovery and Drug Delivery are covered in Real Time, on average up to 12 per year
- See Section
- In 2018, the list of International leading Breakthroughs in BioTechnology Conferences that will be covered in Real Time by Aviva Lev-Ari, PhD, RN includes the following, as confirmed on 1/2018, more will be confirmed in during 2018:
AI & Machine Learning in Clinical Trials, APRIL 12, 2018 PFIZER INNOVATION RESEARCH LAB – CAMBRIDGE, MA
2018 Annual World Medical Innovation Forum Artificial Intelligence April 23–25, 2018 Boston, Massachusetts, Westin Copley Place
12th Annual US-India BioPharma & Healthcare Summit, May 8, 2018, Marriott Cambridge
The 14th Annual Personalized Medicine Conference, November 13 – 15, 2018, Joseph B. Martin Conference Center, HARVARD MEDICAL SCHOOL, Boston
http://www.personalizedmedicinecoalition.org/Events
3. Transformation
- We Focus on Transformative subject matters:
- Examples: We published e-Books on
- Regenerative and Translation Medicine
- Next Generation Sequencing in Genomics (work-in-progress)
- Epigenetics, Genetics and Genomics
- Precision Medicine & Voices of Patients
These contents are timely and among other material are subject to periodic updating. The reports are subject to a rigorous process of investigation, up-to-date reporting, analysis, and interpretation. The curation is done by experts with a perspective on the field allowing for the creation of the scientific CONTEXT that unifies the concept evolution with the breakthrough presented at hand and the future implications to be anticipated.
How we accomplish the Transformation goal:
- Methodology of Curation is Transformative as a Medium for written scientific communication: Synthesis, Analysis and Interpretation
- Experts, Authors, Writers add their depth in thinking on subjects to the breath of materials selected by their expertise to be forming new curations or updating existing ones
- It is transformative in its capacity to accelerated diffusion of scientific innovations process, the curation is done by experts with a perspective on the field allowing for the creation of the scientific CONTEXT that unifies the concept evolution with the breathrough presented at hand and the future implications to be anticipated. In an analogy, it is an expressive medium for creative exposition of multiple combinations of Past, Present, Future tenses in grammar, when the presentation is on the continuous process of discovery.
4. Innovation & Creativity
The content available provides commentaries on each Volume’s Contribution to Medical Education by L.H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN. In addition, it provides a knowledge architecture that features Innovative ideas that tackle pressing challenges in the field of Medical Education. Content includes methodology development for: Curation of Scientific Findings by Experts; Actual Curations, “Mapping” the Medicine Disciplines; Exposition of the Scientific Frontier in Five Specialties in Medicine, and then also pressing challenges in the field of Medical Education such as the Digital Information Explosion in the fields of Life Sciences and Medicine; and finally the Pursuit of Excellence in Content Creation by Curation Methodology for Medical subject matters in multiple areas of the Health Care field.
How we accomplish the Innovation goal:
- Seven factors are presented in Section F, below.
The Body of Work
A. Publication of the BioMedical e-Books e-Series, 2013 – Present
B. BioMedical e-Books e-Series: Multiple Volumes in Five e-Series with Commentaries on each Volume’s Contribution to Medical Education by L.H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
C. electronic Table of Contents (eTOCs) of each Volume in the SIXTEEN-Volume BioMed e-Series
D. Innovative ideas that tackle pressing challenges in the field of Medical Education: Knowledge Architecture
D1 Methodology Development for Content Creation targeted at Medical and Life Sciences Education (Curation of Scientific Findings by Experts)
D2 Methodology Development for Scientific Inquiry in Medicine: Case Studies in a Medical Specialty – Application of the Methodology of Curation to Case Studies – Published as a Book, 2015
D3 Methodology Development for Mapping the Medicine Discipline for Education
D4 Methodology Development for Exposition of the Scientific Frontier in Five Specialties in Medicine
(D4.1, D4.2, D4.3, D4.4, D4.5).
E. Innovative ideas that tackle pressing challenges in the field of Medical Education: Digital Information Explosion in the fields of Life Sciences and Medicine
E1 Open Access Scientific Journal Launch in Biomedicine and Site Statistics:
+1.3 Million eReaders and eSubscribers
E2 Journal Ontology for Knowledge Architecture – +600 Categories of Research
E3 Intellectual Property Vault: Knowledge Base of +5,200 Scientific articles applying the Curation of Scientific Findings Methodology
E4 Scientific Agora: Multi Scientific Comment exchanges between e-Readers Scientists and LPBI’s Scientists/Experts/Authors/Writers
E5 Real Time (RT) Press Coverage of Leading Conferences in BioMedicine: RT Methodology and the Archive
E6 Impact of E5 on E3
F. Innovation & Creativity Demonstrated in the Pursuit of Content Creation by Curation Methodology for Medical Education. For us perfection of the application process of curation methodologies in Medicine is a pursuit of excellence in the creation of content in Life Sciences and in Medicine.
F1 What was accomplished in five years by Development of the Curation Methodology
F2 Method Selection of the Open Access Journal Publishing Medium
F3 Selection of electronic Books vs Hardcover or Softcover type of product
F4 Examples of Creative Article Titles
F5 Examples of Creative eTOCs
F6 Examples of Hierarchical Ontologies created by Experts/Authors/Writers for selected Categories of Research with +500 Articles
F7 Articles of Note in selective Research Topic @PharmaceuticalIntelligence
G. Editor-in-Chief’s Roles and Accomplishments
G1 Curation Methodology Development
G2 Content Creation and Key Opinion Leader (KOL) Recognition
Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Aviva Lev-Ari, PhD, RN
G2.1 Volume of Articles in the Journal and in the 16 Volume-BioMed e-Series
G2.2 Digital Presence
G2.3 Digital KOL Parameters
G3 Team building: Editors and Expert, Authors, Writers
G4 Book Title Generation and Cover Page Design
G5 Style Setting: Instruction manual for Journal, Articles, Books
G6 Annual Workflow Management of Multiple eTOCs – Multi-year Book Publishing Scheduling Plan, 2013 – Present
Justifications for Yidan Prize Nomination
Overview
Dr. Aviva Lev-Ari, PhD, RN has launched in 4/2012 the PharmaceuticalIntelligence.com an Internet-based website as an educational Open Access Online Scientific Journal. On 10/2012 Dr. Lev-Ari, launched a BioMed e-Series of electronic Book in Medicine and Life Sciences which use the Kindle Direct Publishing platform for book publishing by Amazon.com.
The books having evolved for six years from specifically identified topics in Medicine and Biomedical Sciences, including molecular biology, genomics, pharmaceutics and pathophysiology. There have been a number of contributors with the necessary professional competences. The books have been organized into five series that include cardiovascular, genomics, proteomics, pharmacotherapy, cancer and carcinogenesis, infectious disease and immune mechanisms. In addition to these basic disciplines for study there are also important deliberations on the history of medicine and physiology and a focus on the impact of disease on human experience in three books of Series E: Patient-centered Medicine.
The work involved in the writing took many hundreds of hours of study and preparation. These sources have considerable electronic readership (+1.3Million) and have a potential for growing use in teaching of medical students, advanced undergraduate and graduate students in Medical Sciences. Currently, two e-Books are used in curriculum development in Medical Schools in the US. An outreach plan for Deans of Medical Schools and Oncologists and Cardiologists in the Community Hospitals and Clinics is in the making.
The Yidan Prize is awarded for outstanding contributions to education. In this respect the contributions of PharmaceuticalIntelligence.com current and authentic documents is deserving of consideration. Nomination is submitted for recognition as a means in tackling challenges in the field of MEDICAL education, and especially the “Sixteen Volumes in Medicine and Life Sciences” which are LPBI Group’s BioMed e-Series, an initiative of innovative ideas and development of curation methodologies for scientific contents. The BioMedical e-Books e-Series, 2013 – present, includes Commentaries on each Volume’s Contribution to Medical Education by L.H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN. In addition, there is supporting material for an understanding of the role played by electronic Scientific Publishing in mastering the continued progress in Medical Sciences for the electronic exposition of the process used in new scientific content creations. These topics are fully covered in the BioMed e-series. Volume Two in Series A is dedicated to the Curation methodology of scientific findings.
A. Publication of the BioMedical e-Books e-Series:
- Cardiovascular,
- Genomics,
- Cancer,
- BioMed: Metabolomics, Infectious Diseases, Immunology,
- Patient-centered Medicine
This is the link to Amazon.com, Kindle Store’s Page for the 13 volumes published till 12/30/2017
These are the links to Amazon.com, Kindle Store’s Page for each volume
http://www.amazon.com/dp/B00DINFFYC
http://www.amazon.com/dp/B018Q5MCN8
http://www.amazon.com/dp/B018PNHJ84
http://www.amazon.com/dp/B018DHBUO6
http://www.amazon.com/dp/B013RVYR2K
http://www.amazon.com/dp/B012BB0ZF0
http://www.amazon.com/dp/B019UM909A
http://www.amazon.com/dp/B019VH97LU
http://www.amazon.com/dp/B071VQ6YYK
https://www.amazon.com/dp/B075CXHY1B
https://www.amazon.com/dp/B076HGB6MZ
https://www.amazon.com/dp/B078313281
https://www.amazon.com/dp/B078QVDV2W
B. BioMedical e-Books e-Series: Multiple Volumes in Five e-Series with Commentaries on each Volume’s Contribution to Medical Education by L.H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Series A: e-Books on Cardiovascular Diseases
- Cardiovascular Diseases, Volume One: Perspectives on Nitric Oxide in Disease Mechanisms.On com since 6/21/2013, 895 pages
http://www.amazon.com/dp/B00DINFFYC
Series A. Cardiovascular Diseases: Volume 1. Nitric Oxide
Commentary by L.H. Bernstein, MD, FCAP
This volume addresses the essential role of nitric oxide in vascular stress, which includes hypertension and atherosclerosis. Nitric oxide is only one of several substances that have a key role in vascular stress, but the role is large. It has three isoforms, each of which has a special place in organ system development. Nitric oxide has a specific role in oxidative stress that is generated by mitochondrial function, and it is essentially kept in equilibrium. When equilibrium is disrupted, there is a succession of events that leads to cell death and organ dysfunction. This volume elaborates on the consequences of nitric oxide in generalized vascular and in cardiac specific disease.
This book is a series of articles delineating the basic functioning of the NOS isoforms, their production widely by endothelial cells, and the effect of NITRIC OXIDE production by endothelial cells, by neutrophils and macrophages, the effect on intercellular adhesion, and the effect of circulatory shear and turbulence on NITRIC OXIDE production. The essential role of NITRIC OXIDE is seen widely in organ function and in disease development.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
This is the only book on the clinical implications of Nitric oxide on all human body biological systems that covers the biochemistry, the physiology and the pathophysiology representing the frontier of medical science in a clinical context.
- Cardiovascular Diseases, Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation. On Amazon.com since 11/30/2015, 11039 KB
http://www.amazon.com/dp/B018Q5MCN8
Series A. Cardiovascular Diseases: Volume 2. Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation
Commentary by L.H. Bernstein, MD, FCAP
This volume addresses ORIGINAL Research via Content Curation by experts using critical thinking process & interpretation over open access networks, offering better organization and visibility of critical information useful for innovations in academic, clinical, and industrial research.
The main subject of this volume is an elaboration of the methodology for content curation of scientific and more specifically medical literature. It advances a five step process for the curation of the content.
The first evaluation is a review of the affordable care act and the cost of care for cardiovascular disease. The healthcare system needed changes because we have the most costly system, are endowed with advanced technology, and we have inexcusable outcomes in several domains of care, including, infant mortality, and prenatal care – but not in cardiology.
It goes on to consider the conditions that exist in the evolution of cardiovascular disease, among which are not all genetic, but more generally related to calcium signaling and metabolic events that arise during aging. These events have relevance to generalized vascular disease and to cerebral and renal vascular diseases. The material covered includes calcium homeostasis, vascular metabolism, lipid metabolism, conduction disturbances and cardiac dysrhythmias, myocardial infarction, and renal insufficiency.
Curation is an active filtering of the web’s and peer reviewed literature found by such means – immense amount of relevant and irrelevant content. In doing good curation, one does more than simply assign value by presentation of creative work in any category. Answers to specifically focused questions comes from the hard work of many in laboratory settings creatively establishing answers to definitive questions, each a part of the larger knowledge-base of reference.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
In this volume the power of co-curation is harnessed in the format of case studies in Interventional cardiology, Cardiac Medical Imaging and Cardiac Surgery. Unique focus on evolution of stent technology, hybrid operating rooms and outcomes of cardiac surgery compared with interventional cardiology: PCI (stenting) vs CABG (Open Heart Surgery). Primary care physicians in the community find the research findings very useful. The case studies contain material for Curriculum development.
- Cardiovascular Diseases, Volume Three: Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics. On Amazon.com since 11/29/2015, 12333 KB
http://www.amazon.com/dp/B018PNHJ84
Series A. Cardiovascular Diseases: Volume 3 –address the topics of Etiologies of CVD: Epigenetics, Genetics & Genomics
Commentary by L.H. Bernstein, MD, FCAP
These are matters of great interest and have made considerable progress in the last 30 years with respect to cause, risk and biomarkers, and therapies – both surgical and pharmacologic.
Volume 3 is a comprehensive review of recent Original Research on Cardiovascular Diseases: Causes, Risks and Management and related opportunities for Targeted Therapy. It is a rich source of research literature on the genomic influences in cardiovascular disease etiologies. These have variable influence on the etiologies of atherosclerosis, microvascular disease, plaque formation. However, the context is multivariable and includes the environment, dietary factors, level of emotional stress, sleep habits, and the daily activities of living for affected individuals.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
Volume 3 covers Epigenetics, Genetics & Genomics of Cardiovascular Diseases. In one volume a comprehensive exposition of ALL the etiologies for heart disease are analyzed for the cause, the risk, the biomarkers, the determinant vs the life style and diet controllable factors in disease evolution. This is the first book to cover comprehensively Epigenetics consequences.
This volume is used by a Medical School in Philadelphia for curriculum development purposes.
- Cardiovascular Diseases, Volume Four: Regenerative and Translational Medicine: The Therapeutics Promise for Cardiovascular Diseases. On comsince 12/26/2015, 11668 KB
http://www.amazon.com/dp/B019UM909A
Series A. Cardiovascular Diseases: Volume 4 Regenerative and Translational Medicine: The Therapeutics Promise for Cardiovascular Diseases
Commentary by L.H. Bernstein, MD, FCAP
Volume 4 is largely concerned with cardiovascular diseases, Translational Medicine (TM) and post TM as it concerns Regenerative & Pesonalized Medicine (R&PM) in the context of translational medicine and remodeling concepts leading to electric signal conduction, congestive heart failure and myocardial hypertrophy. It further considers protein targets that have been undruggable because of structural features as future pharmaceutical targets. It also discusses tight junctions and ion transport, critical for conduction and excitation contraction coupling. It extends the discussion to cardiomyocyte specific kinases and its role in oxidation related atrial fibrillation. Other PMs are S-nitrosylation and deacetylation, and signaling with oxidative stress that are disrupted in cardiac disease.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
The curation methodology enables the authors/curators to develop one volume that covers the state of science on Regenerative (Stem Cell Implantation) and Translational Medicine (from animal studies to first in Man, clinical trials) with a focus on the Therapeutics Promise for Cardiovascular Diseases. This volume provides latest material for coving these two fields in the classroom. The electronic Table of Contents of the book can serve as a course layout. This book edifies PCP in the community about the frontiers of clinical trials and innovations on Regenerative (Stem Cell Implantation)
Work-in-Progress
Work-in-Progress
Series B: Frontiers in Genomics Research
- VOLUME 1: Genomics Orientations for Personalized Medicine. On comsince 11/23/2015, 11724 KB
http://www.amazon.com/dp/B018DHBUO6
Commentary by L.H. Bernstein, MD, FCAP
What is the Future for Genomics in Clinical Medicine?
Author: Larry H Bernstein, MD, FCAP
Series B: Frontiers in Genomics Research
Series B, VOLUME 1: Genomics Orientations for Personalized Medicine
After the completion of the HGP in 2003, the work was ripe for accelerated discovery, and we have seen new issues in the years since the human genome project (HGP) and ENCODE, and more recently, the 2004 International HapMap project, and 2005 GWAS. This is because there is a now a confluence of circumstances relating to the practice of medicine, the education of physicians, the communication between physician and patients changing from what is referred to “god handing down an edict” to evidence-based medicine. This is also complicated at a time that we have a national state-by-state implementation of a remodeled Medicare and Medicaid plan based on the program already successful in Massachusetts.
In the reorganization, there will be more regional hospital, academic and clinic consolidations, and even possible statewide organizations, movement of patients from inpatient beds sooner with a high skill level of outpatient support, greater concentration of physician staffs aligned to PHO type arrangements, and a need to fill PCP gaps with qualified Advanced Nurse Providers.
All of this is happening now. This is a realignment to meet the needs of the Payor (Fed, HMO, Big Insurance), with tighter margins per stay and critical decisions about capital needs and depreciation, at the same time, required to meet a higher risk of performance standard. Eric topol refers to the need to education of this generation of physicians in Personalized Medicine. But that has never been so easy for those advanced in their careers, and even bright new entries into the profession are faced with productivity guidelines. It is an assignment that will be a new challenge for the Pathology profession, just as the student lab was long ago replaced by the laboratory, with microbiology, blood bank, hematology, chemistry and immunology, to which was added molecular testing. It will be a very challenging undertaking compared to past experience, and it will be a very big adjunct to microscopy, while imaging technology, in the hands of radiology, is undergoing a parallel transformation.
We derive the following major points from what has been presented in this work:
Genomics will become a key component integrated into patient-care, preventive-medicine, and what is going to become a standard of practice for personalized medicine, or individualized-care of a patient defined by individuality, culture, and personal goals for treatment outcomes. A personal goal may be a likely or unlikely point of view in the eye of the observer:
- Let me live with my illness, but relieve my pain
- Give me a realistic time to prepare for dying so I can tie up loose ends
- A cure would be a gift if there adverse effects are minimal
The expanded view of this expectation resides in a more accepting view of what lies ahead and of what is behind. The choice before us lacked clarity in the past. The view was limited, and might still be for some with an unfulfilled life, whether imposed or chosen.
The medical requirement that supercedes all others is:
- Clinical medicine context … clinically guided
- physician/patient relationship … not a consumer relationship
- First do no harm… directly related to priority for care
- must know significance … disease recessive traits ..
- can we offer anything?
common complex diseases…
- both genetic & environmental factors
- not inherited in predictable ways
- gene-gene interactions
- variants usually account for a small amount of risk
examples where both clinical assessment and genomic personalized medicine are expected to realize potential real concordance are:
- macular degeneration
- alzheimer’s disease
- colon cancer
The increased benefit to the pathology-diagnostic imaging -surgical-oncology team is seen as
- tailoring treatment though genomic guidance:
- microscopic doesn’t dictate treatment
- determine choice of treatment
- drug reactions may be avoided
Medical Gutenberg
Eric Topol refers to the “Medical Gutenberg” in a recent lecture in the Medscape series “Creative Destruction of Medicine”. He says ” If we go back to the 1400s and the printing press invented by Johannes Gutenberg, you know how transformative that invention was. The high priests were no longer the only ones who could read; the ability to read books was unleashed to the public. Many years, many centuries have passed since those times, but here in the 21st century we’re getting consumers — the public — to read medical stuff.” He goes on that “now we’re moving from information asymmetry to information parity. This really sets up a unique experience, but it won’t [happen] for all consumers because they’re not all going to want to learn to read and get into this [medical information]. But who has the most vested interest in one’s health if it isn’t that individual, that patient?”
That’s Medical Gutenberg. That’s the opportunity that lies ahead with digital medicine — shifting that information and data to the patient requiring the guidance, knowledge, and experience from physicians.
A Tale of Two Nominal Super-Drugs.
A Success Story? Perhaps too early to know. New York Times reported on March 19 , 2013 that Amgen, had met the primary goal of a Phase 3 clinical trial in patients with advanced melanoma, with 16 percent of the patients in the trial who had the treatment, called talimogene laherparepvec, or TVEC, experienced a significant shrinkage of their tumors that lasted at least six months compared with only 2 percent of the patients in a control group. TVEC is a herpes simplex virus modified in such a way that it replicates in fast-growing cancer cells but not healthy ones, and it also contains an implanted gene for GM-CSF (colony stimulating factor), a protein that stimulates the immune system. When the the replicating viruses cause the cell to burst, freeing the virus and the GM-CSF in the presence of tumor components, it elicits a systemic immune response that can kill cancer cells throughout the body. Recall that this is a late-stage response, and a long term disease free survival is not determined.
A Failure. {Marker for NSCLC Chemo Response Doesn’t Hold Up. by Crystal Phend, MedPage Today, March 20, 2013} A DNA repair biomarker thought to predict benefit from platinum-based chemotherapy in non-small cell lung cancer (NSCLC) doesn’t actually do that good a job. The problem is both technical and due to the inability of the assay to distinguish the key form of the protein for DNA repair. The ERCC1 protein expression level didn’t predict a boost in overall survival (OS) from adjuvant cisplatin (Platinol)-based chemotherapy compared with observation alone in two clinical trials (P=0.23 for interaction). There was no effect seen in the ERCC1-negative group, which was the basis for proposing the protein as a predictive biomarker.
Why is that significant surprise? The inability of the assay to distinguish the key form of the protein for DNA repair, the group reported in the March 21 issue of the NEJM. The antibodies do not have adequate discrimination for therapeutic decision making regarding cisplatin-containing treatment in patients with NSCLC, which requires the specific detection of the unique functional isoform of ERCC1 — ERCC1-202. There are three other isoforms of ERCC1 (excision repair cross-complementation group 1) protein that aren’t critical in fighting the cytotoxic effect of platinum chemotherapy.
So here we have it. It’s not yet, far from the worst of times, but equity barriers remain for a time. The science is critical important, and the implementation of good science can reap huge benefits in time.
New Recommendations for Genetic Reporting
GENNewsHighlights Mar 22, 2013
Finally, there is now emerging a standard of care for providing and reporting of genetic information. The American College of Medical Genetics and Genomics (ACMG) released landmark recommendations on the handling of incidental findings in clinical genome and exome sequencing.This was published within days of completion of this work. It is only the beginning of a process expected to go through many revisions.
http://www.genengnews.com/gen-news-highlights/new-recommendations-for-genetic-reporting/81248136/
A minimum list of genetic conditions, genes, and variants that laboratories performing clinical sequencing should seek and report to the physicians that ordered the testing—regardless of the original reasons for which the test was ordered.
In assembling this list, the Working Group prioritized the disclosure of disorders where:
- Preventative measures and treatments exist
- Patients might not experience symptoms for a long period of time
- The genetic mutations are well recognized and known to have a strong link of causation
Examples of diseases recommended for disclosure include rare hereditary cancers and rare heart diseases that could result in sudden cardiac death.
According to Robert C. Green, MD, medical genecist at Brigham and Women’s Hospital, Harvard, laboratories are looking for guidance on how and what should be communicated to clinicians when results are analyzed. These recommendations will allow a small percentage of families to learn unexpected but potentially life-saving information about an illness they may have never suspected they were at risk for.” The Working Group did not recommend giving patients the choice of whether or not their physician would receive results from the list of recommended incidental findings. This makes sense in the realization that the actual strength of the finding is uncertain. The Working group also recommended that adult-onset conditions on the list be reported, perhaps with the expectation of life-style modification for prevention.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
This volume covers in 21 chapters all the material representing the Frontier of Science in Genomics Orientations for Personalized Medicine. There is no one domain in Medical Education more in need for contents for teaching Medical students than GENOMICS and how this fields applies to Personalized Medicine and Precision Medicine. This volume represents a response for that need in Medical Education.
VOLUME 2: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology
Work-in-Progress
Series C: e-Books on Cancer & Oncology
- Volume 1: Cancer Biology & Genomics for Disease Diagnosis. On comsince 8/11/2015, 13744 KB
http://www.amazon.com/dp/B013RVYR2K
Series C, Volume 1: Cancer Biology and Genomics for Disease Diagnosis, 2015.
Commentary by L.H. Bernstein, MD, FCAP
This book elaborates the worldwide prevalence of cancer as a leading disease. It defines cancer and it discusses the cancer metastasis process. This is essential for medical students and for those undergraduates who have a premedical curriculum with intent on a medical career. In the first chapter there are some interesting presentations about cancer prevention, and a discussion about cancer genetics by James Watson. The genome has been a dominant theme in cancer research for decades following the elucidation of the genetic code and the RNA mediated translation of the code in protein synthesis by the rough endoplasmic reticulum. It discusses melanoma and prostate cancer, which are different. It also considers the role of diet in cancer.
The metabolic pathways that drive cancer is an ongoing investigation. Cancer was first identified in leukemia by Rudolph Virchow, and the discovery of Hodgkin’s lymphoma by Dorothy Hodgkin was another landmark. Chapter 2 begins with differences between cancers, and the tendency for rapid growth and proliferation. There is also a presentation on the mole rat, free of cancer, and of the zebrafish. The work of Otto Warburg in 1924 was monumental. Warburg elucidated the dependence of cancer cells on anaerobic glycolysis and considered cancer to be a fundamental disruption of oxidative metabolism. This work was in part subsumed by the discovery of the genetic code, leading to an emphasis on cancer genetics. However, there has been a resurgence of research on the metabolic events that characterize the Warburg effect.
Furthermore, it poses the question of differences in cancer cell growth, and there is discussion of the stem cell.
Chapter 3 is a significant work on the genetics of cancers. There is a discussion of DNA and the types of cancer, and of JUNK DNA, and the elucidation of complexity in cancer. Then there is the issue of intratumor heterogeneity. Several gastrointestinal types include hepatocellular, pancreas, gastric and salivary, and then breast cancer is discussed. Chapter 4, concerned with epigenetic as well as genetic factors in cancer cell development. Chapter 5 is the metabolism of cancer, which returns to the importance of mitochondria and energy metabolism. It also gives attention to a role of nitric oxide. Chapter 4 elaborates on gastrointestinal (colon and pancreas) and breast cancer, genetics, the BRCA mutations, and tumor progression.
Part 2, Chapters 5 and 6 are concerned with the introduction of specific drugs for cancer cell types. These include breast, gastric, colorectal, kidney, prostate, ovarian, melanoma and leukemia. Chapter 7 elaborates on targeted therapy for specific types of cancer using genomics to identify cell types. This is currently important in developing a personalized medicine.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
Each chapter covers another aspect of the molecular biology of cancers and carcinogenesis. The basic science is presented for Health professionals in training, while it covers all the aspects of life sciences applicable for clinical education: dysfunctional processes and pathophysiological outcomes.
- Volume 2: Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery(Series C Book 2). On com since 5/18/2017, 5408 pages
http://www.amazon.com/dp/B071VQ6YYK
Series C, Volume 2. Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery
Commentary by L.H. Bernstein, MD, FCAP
This e-Book is a comprehensive review and interpretation of recent Original Research on Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery written by Experts, Authors, Writers. The results of Frontier Original Research are gaining value added for the e-Reader by the Methodology of Curation. It may be of special value to both pre-medical undergraduates and medical students, and would be of even greater interest to those who are in an internship in oncology. This is an outstanding follow up on Volume 1, which deals with the basic science that underlies our current knowledge of cancers and carcinogenesis. Volume 2 presents the options available and under development for modalities of therapy.
The first chapter echoes vol 1 in that it is concerned largely with the basic mechanism of cancer evolution, which includes such content as cell growth and regulation, genomics and epigenome, siRNA, and CRISPR/Cas9, which is content that is rapidly expanding, immunity and epigenetic expression.
The second chapter is a detailed consideration of the Warburg effect and the relationship of the glycolytic reliance of the cancer cell to impaired mitochondrial oxidative phosphorylation. It also describes the isocitrate dehydrogenase isoenzyme that is associated with malignancy. There is also the phenomenon that the level of oxidative impairment is related to the rate of proliferation. Finally, it introduces the mechanism of autophagy, the cell death pathway. The impairment of the cancer metabolic identity impairs autophagy, which is related to the term cancer cell “immortality”. It goes on to introduce the concept of personalized medicine based on the fact that cancer cell types have specific identities and development histories. The remaining content gives a thorough examination of specific cancer types.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
This e-Book is the ONLY multidisciplinary comprehensive review and interpretation of recent FIVE Original Research areas on Cancer Therapies: (1) Metabolic, (2) Genomics, (3) Interventional, (4) Immunotherapy and (5) Nanotechnology in Therapy Delivery
From a Medical Education perspective, the contents in Volume 1 and Volume 2 is organized for teaching the Frontier of Science on Cancer: Volume 1: the basic science and Volume 2: the Frontier in Oncological Therapeutic Options.
Nowhere is to be found content interpretation as the ones covered in the following two original 360 degrees curations:
- Warburg Effect Revisited – 2
Writer and Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2015/03/30/warburg-effect-revisited-2/
· Immune-Oncology Molecules In Development & Articles on Topic in @pharmaceuticalintelligence.com
Curators: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN
Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases
- Metabolomics
VOLUME 1: Metabolic Genomics and Pharmaceutics. On Amazon.com since 7/21/2015, 13927 KB
http://www.amazon.com/dp/B012BB0ZF0
- The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications
VOLUME 2: Infectious Diseases and Therapeutics
VOLUME 3: The Immune System and Therapeutics
(Series D: BioMedicine & Immunology) Kindle Edition. On Amazon.com since September 4, 2017, 3747 pages
https://www.amazon.com/dp/B075CXHY1B
Commentary by L.H. Bernstein, MD, FCAP
Series D consists of 3 volumes which contributes to our understanding of metabolism, infectious disease mechanisms, and the immune response. This is essential for our grasping the potential for drug development based on targeting the immune response, and for targeting specific infectious organisms based on interference with essential metabolic pathways. This is of great value for the pre-medical and medical student as well as for postgraduate physicians. Infectious diseases are common worldwide, considering bacterial and viral pathogens. The bacteria have the capability of developing resistance. The viruses have the capability of developing immune resistance to varying degrees, most notable being influenza. This leads to the following alternatives being to block essential pathways of microbial metabolism, which may be followed by a metabolic bypass that constitutes drug resistance. The three volumes are as follows: Metabolic Genomics & Pharmaceutics; Infectious Diseases and Therapeutics; The Immune System and Therapeutics.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
Volume 1: Metabolomics and Microbiome represent the Frontier discoveries between Metabolism, Genomics and Human Immune system. We pioneered in 2015 the publication of the first book on that subject matter containing contents for Medical Education.
Volume 2: Infectious Diseases contains the disease mechanism of Bacterial Infection, Viral Infection, Fungal Infection and Allergy-related Infections. The Therapeutics for each type of infection covers the FDA Approved Drugs for Infections and Infectious Diseases: Bacterial Infection, Viral Infection, Fungal Infection and Allergy-related Infections, 1995 – 2016. Thus, this book becomes a Handbook of therapeutic options per Pathogen classification type. It lands as contents for teaching and curriculum development in this critical domain of PUBLIC HEALTH.
Volume 3: Immune system and Immune response consists of clinical perspectives on the basic science of Immunology. Without the clinician interpretation of this complex body of knowledge the contents would have been left in the domains of basic Biological Sciences: Bacteriology, Virology, Parasitology and Allergy. The Therapeutics explanation coupled with Immune Response types is the roseta stone for Treatment of the immune system, where a failure to identify the treatment may lead to life threatening conditions and failure of the immune system by succumbing the host to pathogen persistence and its survival leading to host’s death. We have included a chapter dedicated to immunotherapy in Cancer. The contents for teaching and curriculum development in this critical domain provide explanations for adoption of Precision Medicine paradigm for advancement of patient-centered medicine.
Series E: Patient-Centered Medicine – LINKS to e-Books & Cover Pages for Volumes 1,2,3,4
- Volume 1: The VOICES of Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures. On com since 10/16/2017, 826 pages
https://www.amazon.com/dp/B076HGB6MZ
Commentary by L.H. Bernstein, MD, FCAP,
Book Co-Editor and contributor of articles on Cancer as a Patient and Physician
This volume is divided into three parts: perceptions of care, the voice of cancer survivors, and the voice of open heart surgery survivors. This is quite difficult because of variation in patients’ ages, outlooks, chronicity and type of condition, and adverse effects of treatments. The best that we can do is look at a small number of narratives.
Perceptions of care are determined by a number of important factors that are dependent on the individual and on the physician, and on the treatment conditions. The individual factors include, but are not limited to patient social status, linguistic factors, cognitive skills and level of education, and communication skills of the care providers. The facilities can be a factor not easily ranked, although that is always a matter for debate. The voices of cancer survivors are presented for both cancer and cardiovascular surgery. These are quite variable and are highly dependent on the specialty treatment organization.
This volume of contributions has focused on the patient’s response to treatment, the expected response to pharmacotherapy, immunotherapy, and radiation therapy. The discussion also entails the difficulties in going beyond diagnosis to a grasp of long term survival. In examining the patient perspective, the patient and the physician have to be in concert with realistic expectations of toxicities, exacerbations, and the possibility of a decline into cachexia.
Individual experiences with cancer, heart disease, and debilitation
It is true in medicine and healthcare that the patient comes first. This calls for a respect for the patient’s best concerns. In the United States (USA), this might be an unusual statement given the great diversity we have as a people. Nevertheless, integration of communities takes time, economic disparities separate individuals and communities within communities, and there are religious and cultural values that divide one person from another. In this respect, families matter, and families may be divided.
There is a range of individual, social and chronic conditions that engage all of us. On the one hand there is the end of life experience. We grow old, but how do we grow old? In the case of cancer, we see that it inflicts pain and suffering at any age. The death of a child is experienced by the parents. Cancer requires some combination of surgery, postoperative chemo- or immunotherapy with local radiation. The chance of recurrence is not small, so the question is always when and how it will be reasserted.
The situation with heart disease is not quite the same. We might like to just be lost in the night, but we don’t have choices. We are also faced with combined chronic systemic conditions, and the heart, kidneys, brain, and lungs are fed by a vascular system. Consequently, it raises the likelihood of multisystem failure. In this situation the possibilities are unclear. The patient with end stage renal disease may go on dialysis in clinic or terminally at home.
The situation is most impressive at the patient end of the process. I still remember a woman of color who had experienced emotional distress and ended several marriages in divorce before she entered the “metropolitan” hospital in my medical school years and was found to have a sudden increase in blood pressure related to a rare adrenaline secreting adenoma of the Organ of Zuckerkandl. She had no visitors during her hospital experience. That was also a time when schizophrenia was not understood, and it also brought shame to a family.
Then there are myths to dispel. When a young woman got pregnant, it was a personal and a family crisis. This is still a situation today that has been highlighted by a juncture disclosed in a presidential contestant interview about whether an abortion, considered a moral issue by the church, is punishable. It also was stated that it would necessitate a return of “back-alley” abortions. It reminded me of the autopsy I performed as a resident on a woman who had pyelonephritis leading to end stage kidney disease. I am a triplet with a sister two years older than myself, and I only learned late in life that my mother had had an aborted pregnancy to alleviate the strain it would place on the family, my father earning a meager living. There is no easy way to conclude this than to say that to the patient, medicine is highly personal.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
Case studies is a method used in Medical Schools for decades. This Volume is very unique by the following aspects: (1) Primary method of data collection was REAL TIME INTERVIEWS conducted by a professional Medical Writer with several stackholders in health care:
Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families.
This volume is the first in a four-volumes e-Series on Patient-Centered Medicine. There are narratives by Patients and there are accounts by Health Care Providers. This volume is unique in the body of existing literature on the subject matter, in the exposition effort to incorporate in tandem, the VOICES of Patients on their Personal Experience with Critical Care and Invasive Medical Procedures. We provide the Personal views of Hospitals CEOs, Health Care Providers, Caregivers and Families in conjunction with the voices of the Patients.
This Volume represents PRIMARY RESEARCH attained by two methodologies:
One, Personal Interviews conducted by the volume Co-Editor, Gail S. Thornton, with Patients and their families facing the diagnosis of a serious medical (not Terminal) illness requiring a major surgery. Ms. Thornton conducted interviews with Hospitals CEOs and other leaders of several Health Care Providers in the US and in other countries.
The other, Personal Accounts and Testimonies of Patients are written by themselves. Some are MDs diagnosed with Cancer, had undergone invasive surgeries as an organ excision, some underwent Open Heart Surgery.
This Volume is AUTHENTIC as has been told by Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families, therefore it represents outstanding Teaching material for Medical Students in training.
This volume is used by a Medical School in Philadelphia for curriculum development in Patient-center Medicine.
- Volume 2: Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders. On com since 12/9/2017, 2862 pages
https://www.amazon.com/dp/B078313281
- Volume 3: Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics. On com since 12/27/2015, 11125 KB
http://www.amazon.com/dp/B019VH97LU
Commentary on Volumes 2 & 3 by L.H. Bernstein, MD, FCAP
Volumes 2 & 3 are of special interest to high school and college students who major in chemistry, molecular biology, or pre-medical studies as well as medical students and postgraduate physicians.
Volume 2 begins the first chapter with a very engaging history of great medical discoveries in much of the 20th century. It traces the discoveries with an emergence of infectious disease followed by endocrinology, including diabetes and pancreatic insulin, and the neuroendocrine axis. As the century develops there are new questions and new solutions, but answers lead to new questions. A large body of Nobel Prize discoveries is laid out and a historical map emerges that connects discoveries in a discovery family. An example of this is the identification of the virus that causes influenza by Opie which is a trigger for the search for the genetic code by Pauling and by Watson. The discovery of the nucleotide sequence of DNA produces a mechanism and the x-ray crystallographic picture. DNA leads to RNA. RNA leads to protein synthesis. The physiology is accompanied by the structure of the cell, which again leads to many related functions.
In addition, there is ever more complexity in the discovery of special types of RNA, such as, inhibiting RNA and silencing RNA. In addition, the discovery of the mechanism of protein synthesis leads to a distinction between the smooth and rough endoplasmic reticulum, after which the cell death mechanism is realized. This has new implications for repair mechanisms and for degenerative diseases as well as for cardiac and vascular response to nitrosative and oxidative stress (Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms), atherosclerosis, and diabetes mellitus. In addition, there is a significant coverage of the expanding knowledge of pharmacology and therapeutics, including nanotechnology, and translational medicine.
Volume 3 continues where Volume 2 left off. It traces the development of clinical chemistry and methods of biological discovery. It begins with a history of infectious diseases, and the therapeutic tie is to immunology, which are both of cellular and antibody nature. A science of immunology developed first with the production of antibodies and the discovery of antisera, which is related to both transfusion reaction and vaccination. It continues further into specific proteins, such as oxygen binding hemoglobins and myoglobin, and this is the path to proteomics. Proteomics considers the structure of protein, protein aggregation, and misfolded protein, such as prion. This leads to a new concept of protein-protein and protein-lipid interactions. The chapter also covers genomics and epigenomics. All of this has been central to the development of modern pharmaceuticals.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
Medical discoveries covered in Volume 2 and Breakthroughs in Physiology are covered in Volume 3. Development of Companion Diagnostics and newly emerging tools for Lab Tests and evidence-based diagnosis are presented. The historical perspectives provided are vital for Medical student development of a longitudinal horizon understanding of the key trajectories that have led to and are leading innovations and progress in Medicine. All Life Sciences students and Historians of Medicine and of Life Sciences, will benefit greatly from a Clinician’s and Pathologist’s perspectives as developed in Volume 2 and 3.
- Volume 4: Medical 3D BioPrinting – The Revolution in Medicine, Technologies for Patient-centered Medicine: From R&D in Biologics to New Medical Devices. On com since 12/30/2017, 1005 pages
https://www.amazon.com/dp/B078QVDV2W
Series E, Volume 4: Medical 3D BioPrinting – The Revolution in Medicine
Commentary by L.H. Bernstein, MD, FCAP
This volume is focused only on the emerging field of 3D medical discovery and its impact on teaching physicians and surgeons, surgical procedures and on potential pharmaceutical applications. It is resident in medical devices and applications at the micro- and the macro- scale. The chapters that follow provide insight into how this development will fuel new drug development, diagnostics, and joint or tissue replacement. This would have applications in joint replacement, burn and trauma surgery, and even possibly cancer treatment.
The potential implications of Nanoscribe’s Photonic Professional GT point to much more important developments then micro-replicated artifacts and figures. This printing technology is being used to develop advanced medical practices that will help with previously difficult processes such as delivering drugs via micro-robots, targeting specific cancer cells, and even assisting in difficult eye operations.
We have covered a broad range of topics in medicine, surgical repair, anatomical presentation and teaching, diagnostics, and even pharmaceutical development. In order to achieve this level of progress the dependence of 2D visualization had to be supplanted by 3D images, even at the molecular level. Examples of this at the macro level are organ replacement, tissue grafts, and introduction of organoids. Examples of this at the micro level are MEMS and sensors in their design, prototyping and manufacturing. In addition, there is an impact on drug development and targeting, nanotechnology, and in drug delivery, and organ transplants (heart, kidney).
The previous series of articles showed a remarkable development of techniques involving tissue and organ remodeling or replacement, a new scale of pharma engineering, an increasing load of FDA approved bioengineering products, the development of biological glue, the application of DNA to polymer engineering, and a new scale of funding for bioengineering. This is the beginning and the continuation of a new age of medical bioengineering.
Commentary on Volume’s Contribution to Medical Education
by Aviva Lev-Ari, PhD, RN
While reading this book title few times, Medical 3D BioPrinting – The Revolution in Medicine, Technologies for Patient-centered Medicine: From R&D in Biologics to New Medical Devices, one realizes that we are facing in 2018, the 4th Revolution in Medicine and in Medical Education. The Gray’s Anatomy ATLAS
is been replace in EVERY Medical School with 3D Printed Anatomical models – the teaching of Anatomy has been revolutionized FOREVER. In Academic Hospital, in Operating Rooms, prior to heart, kidney, lung, liver, and every other organ the CT scan is translated into a 3D Printed Organ for the surgeon to examine the anatomy before the surgery. Tissue repairs for burns, injury, plastic surgery – all are using hydrogels and synthetic materials produced by 3D Printing.
To teach medical students about the Medical 3D BioPrinting – The Revolution in Medicine, one needs a book curated by Clinicians, Scientists and Engineers, https://www.amazon.com/dp/B078QVDV2W
Is our solution in publishing the FIRST book on the topic that covers ENGINEERING aspects, Biomaterials and Medicine applications for development of new Biologics and of New Medical Devices using the 3D BioPrinting technology.
C. electronic Table of Contents (eTOCs) of each Volume in the SIXTEEN-Volume BioMed e-Series
Review of the eTOCs of each of the 16 volumes provides an opportunity for e-Readers EDIFICATION on subject matter completeness of content coverage, innovations in content inclusion, content presentation modalities and future directions in research.
See collection of links to eTOCs for 16 Volumes:
D. Innovative ideas that tackle pressing challenges in the field of Medical Education
Key challenges in the field of Medical Education are:
- Information Explosion – we address it by the Innovative Idea of the Curation Methodology
- High Rate of Information Obsolescence – we address it by two approaches:
- The innovative idea of the Open Access Journal Model and by
- Real Time UPDATES to the online article repository in the Journal from which articles are selected for inclusion into e-Books.
These two approaches minimize the High Rate of Information Obsolescence while offering maximal access to the knowledge published in the Journal
Our response to the pressing challenges in the field of Medical Education, include the following:
D1 Methododlogy Development for Content Creation targeted at Medical and Life Sciences Education
Curation of Scientific Content @Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston
Author: Aviva Lev-Ari, PhD, RN
D2 Methodology Development for Scientific Inquiry in Medicine: Case Studies in a Medical Specialty – Application of the Methodology of Curation to Case Studies in Cardiology – Published as a Book, 2015
Cardiovascular Diseases, Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation. On Amazon.com since 11/30/2015
http://www.amazon.com/dp/B018Q5MCN8
D3 Methodology Development for “Mapping” the Medicine Discipline in the CONTEXT of Health Care for Education Purposes
Our DOMAINS in Electronic Scientific Media
I. Pharmaceutical: Biologics, Small Molecules, Diagnostics
II. Life Sciences: Genomics and Cancer Biology
III. Patient-centered Medicine: Focus on #1: Cardiovascular, #2: Cancer, #3: Physiology: Metabolomics, Immunology
IV. Biomedicine, BioTech, and MedTech (Medical Devices)
V. HealthCare: Patient-centered Medicine and Personalized/Precision Medicine
These are the multiple-volume FIVE e-Series in Medicine and Life Sciences:
- Series A: e-Books on Cardiovascular Diseases
- Series B: Frontiers in Genomics Research
- Series C: e-Books on Cancer & Oncology
- Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases
- Series E: Patient-Centered Medicine – LINKS to e-Books & Cover Pages for Volumes 1,2,3,4
All e-Books are written by Experts, Authors, Writers. The results of Original Research are gaining value added for the e-Reader by the Methodology of Curation. The e-Book’s articles have been published on the Open Access Online Scientific Journal, since April 2012. All new articles on any subject, will continue to be incorporated, as published with periodical updates.
Open Access Online Journal
http://www.pharmaceuticalIntelligence.com
is a scientific, medical and business, multi-expert authoring environment for information syndication in several domains of Life Sciences, Medicine, Pharmaceutical and Healthcare Industries, BioMedicine, Medical Technologies & Devices. Scientific critical interpretations and original articles are written by PhDs, MDs, MD/PhDs, PharmDs, Technical MBAs as Experts, Authors, Writers (EAWs).
D4 Methodology Development for Exposition of the Scientific Frontier in Five Specialties in Medicine (D4.1, D4.2, D4.3, D4.4, D4.5).
- In D1 we presented WHAT the Curation Methodology is.
- In D4 we apply the Curation Methodology to Five Specialties in Medicine
Concentration on Knowledge Interpretation and Integration by Clinicians, Pathologists (MDs, MD/PhDs) and Scientist/Experts (PhDs, PharmD) of the following aspects of Health Care:
- Medical Disease Diagnosis,
- Diagnostic Methods and Biomarkers,
- Genomics
- Therapeutics
- Personalized Medicine and Patient-center Health Care Delivery.
The Five Specialties in Medicine consists of:
D4.1 Cardiovascular Diseases
- Perspectives on Nitric Oxide in Disease Mechanisms, Nobel Prize, 1998 “Molecule of the Year” in 1992 by the journal It has crucial biochemical functions in the Cardiovascular system.
- Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics
- Regenerative and Translational Medicine: The Therapeutics Promise for Cardiovascular Diseases.
- Pharmacological Agents and Pharmacogenomics in Treatment of Cardiovascular Diseases
- Interventional Cardiology and Cardiac Surgery for Disease Diagnosis and Guidance of Treatment
D4.2 Genomics Research and Applications in Medicine
- Genomics Orientations for Personalized Medicine
- Latest in Genomics Methodologies for Therapeutics: Gene Editing, Next Generation Sequencing & BioInformatics, Simulations and the Genome Ontology
D4.3 Cancer & Oncology
- Cancer Biology & Genomics for Disease Diagnosis
- Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery
D4.4 BioMedicine – Metabolomics, Immunology, Infectious Diseases
- Metabolomics: Metabolic Genomics and Pharmaceutics
- The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications
D4.5 Patient-Centered Medicine – Newest Paradigm in Healthcare Delivery
- The VOICES of Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures
- Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders.
- Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics.
- Medical 3D BioPrinting – The Revolution in Medicine, Technologies for Patient-centered Medicine: From R&D in Biologics to New Medical Devices
In Section D, above, we explained the pressing need to generate a knowledge architecture to handle the complexity of contents in Medicine and Life Sciences, as well as the need for a methodology to compress the volume of information. Our response is the Curation Methodology.
In Section E, we present six innovative strategies to tackle the challenge of Digital Information Explosion in the field of Medical education:
E. Innovative ideas that tackle pressing challenges in the field of Medical education: Digital Information Explosion
E1 Access to CURATED Scientific Knowledge is maximized by Open Access Scientific Journal Launch in Biomedicine
Site Statistics reflect the REACH achieved following the ACCESS provided by the Open Access Scientific Journal Launch in Biomedicine:
+1.3 Million e-Readers and Subscribers
[On 1/29/2018 – 1,373,977 views 7,283 scientific comments]
E2 Journal Ontology for Knowledge Architecture, +600 Categories of Research
[On 1/29/2018 – 611 Categories]
E3 Intellectual Property Vault (IPV): Building Capacity for Knowledge Reach of Scientific Content Created by using the Curation Methodology
The relevance of IPV to Medical Education is vast. ANY article in the Journal or in any e-book that is a curation (not a reporting) represents ORIGINAL curation of the frontier of knowledge. In Medical Education each curation in the format of a Journal Article could serve as
- a Template for building the contents in curriculum on the subject of the article(s).
- the eTOCs of each e-Book could serve as a Template for building the contents in curriculum on an entire COURSE on the subject of the e-Book. It is been used for that very scope at a Medical School in PA, Series A, Volume 3 and Series E, Volume 1.
EXAMPLE: In teaching Cardiology Residents on Acute Coronary Syndromes the following CURATIONS on High Sensitivity Troponin (hs cTn) Assays would save weeks/months of secondary investigation by the Cardiology Professor planning to teach this subject:
- Previously undiscerned value of hs-troponin
Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2016/06/18/previously-undiscerned-value-of-hs-troponin/
- Recent Insights into the High Sensitivity Troponins for Acute Coronary Syndromes
Curator: Larry H Bernstein, MD, FCAP
- Dealing with the Use of the High Sensitivity Troponin (hs cTn) Assays: Preparing the United States for High-Sensitivity Cardiac Troponin Assays
Author and Curator: Larry H Bernstein, MD, FCAP and Author and Curator: Aviva Lev-Ari, PhD, RD
https://pharmaceuticalintelligence.com/2013/05/18/dealing-with-the-use-of-the-hs-ctn-assays/
- Preparing the United States for High-Sensitivity Cardiac Troponin Assays
Curator: Larry H Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2013/06/13/high-sensitivity-cardiac-troponin-assays/
Our Journal’s Knowledge Base applying the Curation of Scientific Findings Methodology on peer-reviewed published Research in Medicine consists of +5,200 Scientific articles
[On 1/29/2018 – 5,246 scientific articles]
E4 Scientific Agora: Comment exchanges between e-Readers Scientists and LPBI’s Scientists/Experts/Authors/Writers
[On 1/29/2018 – 7,283 comments]
The relevance of the Scientific Agora to Medical Education is vast. The Open Access Journal allows EVERY Scientist on the internet the GLOBAL reach and access to Open Access published scientific contents NOT only to the subscription payer base of the Journal. If you don’t have a HIGH FEE subscription you got NO access to content in the Journal, you can’t participate in Multiple Comment Exchanges. In the Medical Education context – COMMENTS are the medium to debate with peers. See, below.
Multiple Comment Exchanges on an article in the Journal: An Example
Personalized Medicine: Cancer Cell Biology and Minimally Invasive Surgery (MIS)
Curator: Aviva Lev-Ari, PhD, RN
This article generated a Scientific Exchange of 24 Comments, some scholarly comments are quite lengthy
The 24 Responses in the Comment Section of the article
GREAT work.
I’ll read and comment later on
Highlights of The 2012 Johns Hopkins Prostate Disorders White Paper include:
A promising new treatment for men with frequent nighttime urination.
Answers to 8 common questions about sacral nerve stimulation for lower urinary tract symptoms.
Surprising research on the link between smoking and prostate cancer recurrence.
How men who drink 6 cups of coffee a day or more may reduce their risk of aggressive prostate cancer.
Should you have a PSA screening test? Answers to important questions on the controversial USPSTF recommendation.
Watchful waiting or radical prostatectomy for men with early-stage prostate cancer? What the research suggests.
A look at state-of-the-art surveillance strategies for men on active surveillance for prostate cancer.
Locally advanced prostate cancer: Will you benefit from radiation and hormones?
New drug offers hope for men with metastatic castrate-resistant prostate cancer.
Behavioral therapy for incontinence: Why it might be worth a try.
You’ll also get the latest news on benign prostatic enlargement (BPE), also known as benign prostatic hyperplasia (BPH) and prostatitis:
What’s your Prostate Symptom Score? Here’s a quick quiz you can take right now to determine if you should seek treatment for your enlarged prostate.
Your surgical choices: a close look at simple prostatectomy, transurethral prostatectomy and open prostatectomy.
New warnings about 5-alpha-reductase inhibitors and aggressive prostate cancer.
Promising technique.
INCORE pointed out in detail about the general problem judging response and the stil missing quality in standardization:
I did research in response evaluation and prediction for about 15y now and being honest: neither the clinical, nor the molecular biological data proved significant benefit in changing a strategy in patient diagnosis and / or treatment. I would state: this brings us back on the ground and not upon the sky. Additionally it means: we have to ´work harder on that and the WHO has to take responsibility: clinicians use a reponse classification without knowing, that this is just related to “ONE” experiment from the 70′s and that this experiment never had been rescrutinized (please read the Editorial I provided – we use a clinical response classification since more than 30 years worldwide (Miller et al. Cancer 1981) but it is useless !
Dr. BB
Thank you for your comment.
Dr. Nir will reply to your comment.
Regarding the Response Classification in use, it seems that the College of Oncology should champion a task force to revisit the Best Practice in use in this domain and issue a revised version or a new effort for a a new classification system for Clinical Response to treatment in Cancer.
I’m sorry that I was looking for this paper again earlier and didn’t find it. I answered my view on your article earlier.
This is a method demonstration, but not a proof of concept by any means. It adds to the cacophany of approaches, and in a much larger study would prove to be beneficial in treatment, but not a cure for serious prostate cancer because it is unlikely that it can get beyond the margin, and also because there is overtreatment at the cutoff of PSA at 4.0. There is now a proved prediction model that went to press some 4 months ago. I think that the pathologist has to see the tissue, and the standard in pathology now is for any result that is cancer, two pathologist or a group sitting together should see it. It’s not an easy diagnosis.
Björn LDM Brücher, Anton Bilchik, Aviram Nissan, Itzhak Avital, & Alexander Stojadinovic. Tumor response criteria: are they appropriate? Future Oncol. (2012) 8(8), 903–906. 10.2217/FON.12.78. ISSN 1479-6694.
..Tumor heterogeneity is a ubiquitous phemomenon. In particular, there are important differences among the various types of gastrointestinal (GI) cancers in terms of tumor biology, treatment response and prognosis.
..This forms the principal basis for targeted therapy directed by tumor-specific testing at either the gene or protein level. Despite rapid advances in our understanding of targeted therapy for GI cancers, the impact on cancer survival has been marginal.
..Can tumor response to therapy be predicted, thereby improving the selection of patients for cancer treatment?
..In 2000 theNCI with the European Association for Research and Treatment of Cancer, proposed a replacement of 2D measurement with a decrease in the largest tumor diameter by 30% in one dimension. Tumor response as defined would translate into a 50% decrease for a spherical lesion
..We must rethink how we may better determine treatment response in a reliable, reproducible way that is aimed at individualizing the therapy of cancer patients.
..we must change the tools we use to assess tumor response. The new modality should be based on empirical evidence that translates into relevant and meaningful clinical outcome data.
..This becomes a conundrum of sorts in an era of ‘minimally invasive treatment’.
..integrated multidisciplinary panel of international experts – not sure that that will do it
Several years ago i heard Stamey present the totality of his work at Stanford, with great disappointment over hsPSA that they pioneered in. The outcomes were disappointing.
I had published a review of all of our cases reviewed for 1 year with Marguerite Pinto.
There’s a reason that the physicians line up outside of her office for her opinion.
The review showed that a PSA over 24 ng/ml is predictive of bone metastasis. Any result over 10 was as likely to be prostatitis, BPH or cancer.
I did an ordinal regression in the next study with Gustave Davis using a bivariate ordinal regression to predict lymph node metastasis using the PSA and the Gleason score. It was better than any univariate model, but there was no followup.
I reviewed a paper for Clin Biochemistry (Elsevier) on a new method for PSA, very different than what we are familiar with. It was the most elegant paper I have seen in the treatment of the data. The model could predict post procedural time to recurrence to 8 years.
I hope we are in agreement on the fact that imaging guided interventions are needed for better treatment outcome. The point I’m trying to make in this post is that people are investing in developing imaging guided intervention and it is making progress.
Over diagnosis and over treatment is another issue altogether. I think that many of my other posts are dealing with that.
Tumor response criteria: are they appropriate?
Future Oncology 2012; 8(8): 903-906 , DOI 10.2217/fon.12.78 (doi:10.2217/fon.12.78)
Björn LDM Brücher, Anton Bilchik, Aviram Nissan, Itzhak Avital & Alexander Stojadinovic
Tumor heterogeneity is a problematic because of differences among the metabolic variety among types of gastrointestinal (GI) cancers, confounding treatment response and prognosis.
This is in response to … a group of investigators from Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada who evaluate the feasibility and safety of magnetic resonance (MR) imaging–controlled transurethral ultrasound therapy for prostate cancer in humans. Their study’s objective was to prove that using real-time MRI guidance of HIFU treatment is possible and it guarantees that the location of ablated tissue indeed corresponds to the locations planned for treatment.
1. There is a difference between expected response to esophageal or gastric neoplasms both biologically and in expected response, even given variability within a class. The expected time to recurrence is usually longer in the latter case, but the confounders are – age at time of discovery, biological time of detection, presence of lymph node and/or distant metastasis, microscopic vascular invasion.
2. There is a long latent period in abdominal cancers before discovery, unless a lesion is found incidentally in surgery for another reason.
3. The undeniable reality is that it is not difficult to identify the main lesion, but it is difficult to identify adjacent epithelium that is at risk (transitional or pretransitional). Pathologists have a very good idea about precancerous cervical neoplasia.
The heterogeneity rests within each tumor and between the primary and metastatic sites, which is expected to be improved by targeted therapy directed by tumor-specific testing. Despite rapid advances in our understanding of targeted therapy for GI cancers, the impact on cancer survival has been marginal.
The heterogeneity is a problem that will take at least another decade to unravel because of the number of signaling pathways and the crosstalk that is specifically at issue.
I must refer back to the work of Frank Dixon, Herschel Sidransky, and others, who did much to develop a concept of neoplasia occurring in several stages – minimal deviation and fast growing. These have differences in growth rates, anaplasia, and biochemical. This resembles the multiple “hit” theory that is described in “systemic inflammatory” disease leading to a final stage, as in sepsis and septic shock.
In 1920, Otto Warburg received the Nobel Prize for his work on respiration. He postulated that cancer cells become anaerobic compared with their normal counterpart that uses aerobic respiration to meet most energy needs. He attributed this to “mitochondrial dysfunction. In fact, we now think that in response to oxidative stress, the mitochondrion relies on the Lynen Cycle to make more cells and the major source of energy becomes glycolytic, which is at the expense of the lean body mass (muscle), which produces gluconeogenic precursors from muscle proteolysis (cancer cachexia). There is a loss of about 26 ATP ~Ps in the transition.
The mitochondrial gene expression system includes the mitochondrial genome, mitochondrial ribosomes, and the transcription and translation machinery needed to regulate and conduct gene expression as well as mtDNA replication and repair. Machinery involved in energetics includes the enzymes of the Kreb’s citric acid or TCA (tricarboxylic acid) cycle, some of the enzymes involved in fatty acid catabolism (β-oxidation), and the proteins needed to help regulate these systems. The inner membrane is central to mitochondrial physiology and, as such, contains multiple protein systems of interest. These include the protein complexes involved in the electron transport component of oxidative phosphorylation and proteins involved in substrate and ion transport.
Mitochondrial roles in, and effects on, cellular homeostasis extend far beyond the production of ATP, but the transformation of energy is central to most mitochondrial functions. Reducing equivalents are also used for anabolic reactions. The energy produced by mitochondria is most commonly thought of to come from the pyruvate that results from glycolysis, but it is important to keep in mind that the chemical energy contained in both fats and amino acids can also be converted into NADH and FADH2 through mitochondrial pathways. The major mechanism for harvesting energy from fats is β-oxidation; the major mechanism for harvesting energy from amino acids and pyruvate is the TCA cycle. Once the chemical energy has been transformed into NADH and FADH2 (also discovered by Warburg and the basis for a second Nobel nomination in 1934), these compounds are fed into the mitochondrial respiratory chain.
The hydroxyl free radical is extremely reactive. It will react with most, if not all, compounds found in the living cell (including DNA, proteins, lipids and a host of small molecules). The hydroxyl free radical is so aggressive that it will react within 5 (or so) molecular diameters from its site of production. The damage caused by it, therefore, is very site specific. The reactions of the hydroxyl free radical can be classified as hydrogen abstraction, electron transfer, and addition.
The formation of the hydroxyl free radical can be disastrous for living organisms. Unlike superoxide and hydrogen peroxide, which are mainly controlled enzymatically, the hydroxyl free radical is far too reactive to be restricted in such a way – it will even attack antioxidant enzymes. Instead, biological defenses have evolved that reduce the chance that the hydroxyl free radical will be produced and, as nothing is perfect, to repair damage.
Currently, some endogenous markers are being proposed as useful measures of total “oxidative stress” e.g., 8-hydroxy-2’deoxyguanosine in urine. The ideal scavenger must be non-toxic, have limited or no biological activity, readily reach the site of hydroxyl free radical production (i.e., pass through barriers such as the blood-brain barrier), react rapidly with the free radical, be specific for this radical, and neither the scavenger nor its product(s) should undergo further metabolism.
Nitric oxide has a single unpaired electron in its π*2p antibonding orbital and is therefore paramagnetic. This unpaired electron also weakens the overall bonding seen in diatomic nitrogen molecules so that the nitrogen and oxygen atoms are joined by only 2.5 bonds. The structure of nitric oxide is a resonance hybrid of two forms.
In living organisms nitric oxide is produced enzymatically. Microbes can generate nitric oxide by the reduction of nitrite or oxidation of ammonia. In mammals nitric oxide is produced by stepwise oxidation of L-arginine catalyzed by nitric oxide synthase (NOS). Nitric oxide is formed from the guanidino nitrogen of the L-arginine in a reaction that consumes five electrons and requires flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) tetrahydrobiopterin (BH4), and iron protoporphyrin IX as cofactors. The primary product of NOS activity may be the nitroxyl anion that is then converted to nitric oxide by electron acceptors.
The thiol-disulfide redox couple is very important to oxidative metabolism. GSH is a reducing cofactor for glutathione peroxidase, an antioxidant enzyme responsible for the destruction of hydrogen peroxide. Thiols and disulfides can readily undergo exchange reactions, forming mixed disulfides. Thiol-disulfide exchange is biologically very important. For example, GSH can react with protein cystine groups and influence the correct folding of proteins, and it GSH may play a direct role in cellular signaling through thiol-disulfide exchange reactions with membrane bound receptor proteins (e.g., the insulin receptor complex), transcription factors (e.g., nuclear factor κB), and regulatory proteins in cells. Conditions that alter the redox status of the cell can have important consequences on cellular function.
So the complexity of life is not yet unraveled.
Can tumor response to therapy be predicted, thereby improving the selection of patients for cancer treatment?
The goal is not just complete response. Histopathological response seems to be related post-treatment histopathological assessment but it is not free from the challenge of accurately determining treatment response, as this method cannot delineate whether or not there are residual cancer cells. Functional imaging to assess metabolic response by 18-fluorodeoxyglucose PET also has its limits, as the results are impacted significantly by several variables:
- tumor type
• sizing
• doubling time
• anaplasia?
• extent of tumor necrosis
• type of antitumor therapy and the time when response was determined.
The new modality should be based on individualized histopathology as well as tumor molecular, genetic and functional characteristics, and individual patients’ characteristics, a greater challenge in an era of ‘minimally invasive treatment’.
This listing suggests that for every cancer the following data has to be collected (except doubling time). If there are five variables, the classification based on these alone would calculate to be very sizable based on Eugene Rypka’s feature extraction and classification. But looking forward, time to remission and disease free survival are additionally important. Treatment for cure is not the endpoint, but the best that can be done is to extend the time of survival to a realistic long term goal and retain a quality of life.
Brücher BLDM, Piso P, Verwaal V et al. Peritoneal carcinomatosis: overview and basics. Cancer Invest.30(3),209–224 (2012).
Brücher BLDM, Swisher S, Königsrainer A et al. Response to preoperative therapy in upper gastrointestinal cancers. Ann. Surg. Oncol.16(4),878–886 (2009).
Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer47(1),207–214 (1981).
Therasse P, Arbuck SG, Eisenhauer EA et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl Cancer Inst.92(3),205–216 (2000).
Brücher BLDM, Becker K, Lordick F et al. The clinical impact of histopathological response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas. Cancer106(10),2119–2127 (2006).
Dr. Larry,
Thank you for this comment.
Please carry it as a stand alone post, Dr. Ritu will refer to it and reference it in her FORTHCOMING post on Tumor Response which will integrate multiple sources.
Please execute my instruction
Thank you
Thank you Larry for this educating comment. It explains very well why the Canadian investigators did not try to measure therapy response!
What they have demonstrated is the technological feasibility of coupling a treatment device to an imaging device and use that in order to guide the treatment to the right place.
the issue of “choice of treatment” to which you are referring is not in the scope of this publication.
The point is: if one treatment modality can be guided, other can as well! This should encourage others, to try and develop imaging-based treatment guidance systems.
The crux of the matter in terms of capability is that the cancer tissue, adjacent tissue, and the fibrous matrix are all in transition to the cancerous state. It is taught to resect leaving “free margin”, which is better aesthetically, and has had success in breast surgery. The dilemma is that the patient may return, but how soon?
Correct. The philosophy behind lumpectomy is preserving quality of life. It was Prof. Veronesi (IEO) who introduced this method 30 years ago noticing that in the majority of cases, the patient will die from something else before presenting recurrence of breast cancer..
It is well established that when the resection margins are declared by a pathologist (as good as he/she could be) as “free of cancer”, the probability of recurrence is much lower than otherwise.
Dr. Larry,
To assist Dr. Ritu, PLEASE carry ALL your comments above into a stand alone post and ADD to it your comment on my post on MIS
Thank you
- edit this on December 5, 2012 at 2:34 PM | Replysjwilliamspa
Great post! Dr. Nir, can the ultrasound be used in conjunction with PET scanning as well to determine a spatial and functional map of the tumor. With a disease like serous ovarian cancer we typically see an intraperitoneal carcimatosis and it appears that clinicians are wanting to use fluorogenic probes and fiberoptics to visualize the numerous nodules located within the cavity Also is the technique being used mainy for surgery or image guided radiotherapy or can you use this for detecting response to various chemotherapeutics including immunotherapy.
Ultrasound can and is actually used in conjunction with PET scanning in many cases. The choice of using ultrasound is always left to the practitioner! Being a non-invasive, low cost procedure makes the use of ultrasound a non-issue. The down-side is that because it is so easy to access and operate, nobody bothers to develop rigorous guidelines about using it and the benefits remains the property of individuals.
In regards to the possibility of screening for ovarian cancer and characterising pelvic masses using ultrasound I can refer you to scientific work in which I was involved:
- VAES (E.), MANCHANDA (R), AUTIER, NIR (R), NIR (D.), BLEIBERG (H.), ROBERT (A.), MENON (U.). Differential diagnosis of adnexal masses: Sequential use of the Risk of Malignancy Index and a novel computer aided diagnostic tool. Published in Ultrasound in Obstetrics & Gynecology. Issue 1 (January). Vol. 39. Page(s): 91-98.
- VAES (E.), MANCHANDA (R), NIR (R), NIR (D.), BLEIBERG (H.), AUTIER (P.), MENON (U.), ROBERT (A.). Mathematical models to discriminate between benign and malignant adnexal masses: potential diagnostic improvement using Ovarian HistoScanning. Published in International Journal of Gynecologic Cancer (IJGC). Issue 1. Vol. 21. Page(s): 35-43.
- LUCIDARME (0.), AKAKPO (J.-P.), GRANBERG (S.), SIDERI (M.), LEVAVI (H.), SCHNEIDER (A.), AUTIER (P.), NIR (D.), BLEIBERG (H.). A new computer aided diagnostic tool for non-invasive characterisation of malignant ovarian masses: Results of a multicentre validation study. Published in European Radiology. Issue 8. Vol. 20. Page(s): 1822-1830.
Dror Nir, PhD
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totally true and I am very thankful for these brilliant comments.
Remember: 10 years ago: every cancer researcher stated: “look at the tumor cells only – forget the stroma”. The era of laser-captured tumor-cell dissection started. Now , everyone knows: it is a system we are looking at and viewing and analyzing tumor cells only is really not enough.
So if we would be honest, we would have to declare, that all data, which had been produced 13-8years ago, dealing with laser capture microdissection, that al these data would need a re-scrutinization, cause the influence of the stroma was “forgotten”. I ‘d better not try thinking about the waisted millions of dollars.
If we keep on being honest: the surgeon looks at the “free margin” in a kind of reductionable model, the pathologist is more the control instance. I personally see the pathologist as “the control instance” of surgical quality. Therefore, not the wish of the surgeon is important, the objective way of looking into problems or challenges. Can a pathologist always state, if a R0-resection had been performed ?
The use of the Resectability Classification: There had been many many surrogate marker analysis – nothing new. BUT never a real substantial well tought through structured analysis had been done: mm by mm by mm by mm and afterwards analyzing that by a ROC analysis. BUt against which goldstandard ? If you perform statistically a ROC analysis – you need a golstandard to compare to. Therefore what is the real R0-resectiòn? It had been not proven. It just had been stated in this or that tumor entity that this or that margin with this margin free mm distance or that mm distance is enough and it had been declared as “the real R0-classification”. In some organs it is very very difficult and we all (surgeons, pathologists, clinicians) that we always get to the limit, if we try interpretating the R-classification within the 3rd dimension. Often it is just declared and stated.
Otherwise: if lymph nodes are negative it does not mean, lymph nodes are really negative, cause up to 38% for example in upper GI cancers have histological negative lymph nodes, but immunohistochemical positive lymph nodes. And this had been also shown by Stojadinovic at el analyzing the ultrastaging in colorectal cancer. So the 4th dimension of cancer – the lymph nodes / the lymphatic vessel invasion are much more important than just a TNM classification, which unfortunately does often not reflect real tumor biology.
AS we see: cancer has multifactorial reasons and it is necessary taking the challenge performing high sophisticated research by a multifactorial and multidisciplinary manner.
Again my deep and heartly thanks for that productive and excellent discussion !
Dr. BB,
Thank you for your comment.
Multidisciplinary perspectives have illuminated the discussion on the pages of this Journal.
Eager to review Dr. Ritu’s forthcoming paper – the topic has a life of its own and is embodied in your statement:
“the 4th dimension of cancer – the lymph nodes / the lymphatic vessel invasion are much more important than just a TNM classification, which unfortunately does often not reflect real tumor biology.”
Thank you BB for your comment. You have touched the core limitation of healthcare professionals: how do we know that we know!
Do we have a reference to each of the test we perform?
Do we have objective and standardise quality measures?
Do we see what is out-there or are we imagining?
The good news: Everyday we can “think” that we learned something new. We should be happy with that, even if it is means that we learned that yesterday’s truth is not true any-more and even if we are likely to be wrong again…:)
But still, in the last decades, lots of progress was made….
- edit this on December 11, 2012 at 2:34 AM | Replyritusaxena
Dr. Nir,
I thoroughly enjoyed reading your post as well as the comments that your post has attracted. There were different points of view and each one has been supported with relevant examples in the literature. Here are my two cents on the discussion:
The paper that you have discussed had the objective of finding out whether real-time MRI guidance of treatment was even possible and if yes, and also if the treatment could be performed in accurate location of the ROI? The data reveals they were pretty successful in accomplishing their objective and of course that gives hope to the imaging-based targeted therapies.
Whether the ROI is defined properly and if it accounts for the real tumor cure, is a different question. Role of pathologists and the histological analysis they bring about to the table cannot be ruled out, and the absence of a defined line between the tumor and the stromal region in the vicinity is well documented. However, that cannot rule out the value and scope of imaging-based detection and targeted therapy. After all, it is seminal in guiding minimally invasive surgery. As another arm of personalized medicine-based cure for cancer, molecular biologists at MD Anderson have suggested molecular and genetic profiling of the tumor to determine genetic aberrations on the basis of which matched-therapy could be recommended to patients. When phase I trial was conducted, the results were obtained were encouraging and the survival rate was better in matched-therapy patients compared to unmatched patients. Therefore, everytime there is more to consider when treating a cancer patient and who knows a combination of views of oncologists, pathologists, molecular biologists, geneticists, surgeons would device improvised protocols for diagnosis and treatment. It is always going to be complicated and generalizations would never give an answer. Smart interpretations of therapies – imaging-based or others would always be required!
Ritu
Dr. Nir,
One of your earlier comments, mentioned the non invasiveness of ultrasound, thus, it’s prevalence in use for diagnosis.
This may be true for other or all areas with the exception of Mammography screening. In this field, an ultrasound is performed only if a suspected area of calcification or a lump has been detected in the routine or patient-initiated request for ad hoc mammography secondery to patient complain of pain or patient report of suspected lump.
Ultrasound in this field repserents ascalation and two radiologists review.
It in routine use for Breast biopsy.
Thanks Ritu for this supporting comment. The worst enemy of finding solutions is doing nothing while using the excuse of looking for the “ultimate solution” . Personally, I believe in combining methods and improving clinical assessment based on information fusion. Being able to predict, and then timely track the response to treatment is a major issue that affects survival and costs!
Judging the ‘Tumor response’- there is more food for thought
13 Responses
- edit this on December 4, 2012 at 2:25 PM | Replysjwilliamspa
Dr. Sanexa
you have brought up an interesting and very clinically relevant point: what is the best measurement of response and 2) how perspectives among oncologists and other professionals differ on this issues given their expertise in their respective subspecialties (immunologist versus oncologist. The advent of functional measurements of tumors (PET etc.) seems extremely important in the therapeutic use AND in the development of these types of compounds since usually a response presents (in cases of solid tumors) as either a lack of growth of the tumor or tumor shrinkage. Did the authors include an in-depth discussion of the rapidity of onset of resistance with these types of compounds?
Thanks for the posting.
- edit this on December 4, 2012 at 4:48 PM | Reply ritusaxena
Dr. Williams,
Thanks for your comment on the post. The editorial brings to attention a view that although PET and other imaging methods provide vital information on tumor growth, shrinkage in response to a therapy, however, there are more aspects to consider including genetic and molecular characteristics of tumor.
It was an editorial review and the authors did not include any in-depth discussion on the rapidity of onset of resistance with these types of compounds as the focus was primarily on interpreting tumor response.
I am glad you found the contents of the write-up informative.
Thanks again!
Ritu
Thank you for your wonderful comment and interpretation. Dr.Sanexa made a brilliant comment.
May I allow myself putting my finger deeper into this wound ? Cancer patients deserve it.
It had been already pointed out by international experts from Munich, Tokyo, Hong-Kong and Houston, dealing with upper GI cancer, that the actual response criteria are not appropriate and moreover: the clinical response criteria in use seem rather to function as an alibi, than helping to differentiate and / or discriminate tumor biology (Ann Surg Oncol 2009):
http://www.ncbi.nlm.nih.gov/pubmed/19194759
The response data in a phase-II-trial (one tumor entity, one histology, one treatment, one group) revealed: clinical response evaluation according to the WHO-criteria is not appropriate to determine response:
http://www.ncbi.nlm.nih.gov/pubmed/15498642
Of course, there was a time, when it seemed to be useful and this also has to be respected.
There is another challenge: using statistically a ROC and resulting in thresholds. This was, is and always be “a clinical decision only” and not the decision of the statistician. The clinician tells the statistician, what decision, he wants to make – the responsibility is enormous. Getting back to the roots:
After the main results of the Munich-group had been published 2001 (Ann Surg) and 2004 (J Clin Oncol):
http://www.ncbi.nlm.nih.gov/pubmed/11224616
http://www.ncbi.nlm.nih.gov/pubmed/14990646
the first reaction in the community was: to difficult, can’t be, not re-evaluated, etc.. However, all evaluated cut-offs / thresholds had been later proven to be the real and best ones by the MD Anderson Cancer Center in Houston, Texas. Jaffer Ajani – a great and critical oncologist – pushed that together with Steve Swisher and they found the same results. Than the upper GI stakeholders went an uncommon way in science: they re-scrutinized their findings. Meanwhile the Goldstandard using histopathology as the basis-criterion had been published in Cancer 2006.
http://www.ncbi.nlm.nih.gov/pubmed/16607651
Not every author, who was at the authorlist in 2001 and 2004 wanted to be a part of this analysis and publication ! Why ? Everyone should judge that by himself.
The data of this analysis had been submitted to the New England Journal of Medicine. In the 2nd review stage process, the manuscript was rejected. The Ann Surg Oncol accepted the publication: the re-scrutinized data resulted in another interesting finding: in the future maybe “one PET-scan” might be appropriate predicting the patient’s response.
Where are we now ?
The level of evidence using the response criteria is very low: Miller’s (Cancer 1981) publication belonged to ”one single” experiment from Moertel (Cancer 1976). During that time, there was no definition of “experiences” rather than “oncologists”. These terms had not been in use during that time.
Additionally they resulted in a (scientifically weak) change of the classification, published by Therasse (J Natl Cancer Inst 2000). Targeted therapy did not result in a change so far. In 2009, the international upper GI experts sent their publication of the Ann Surg Oncol 2009 to the WHO but without any kind of reaction.
Using molecular biological predictive markers within the last 10years all seem to have potential.
http://www.ncbi.nlm.nih.gov/pubmed/20012971
http://www.ncbi.nlm.nih.gov/pubmed/18704459
http://www.ncbi.nlm.nih.gov/pubmed/17940507
http://www.ncbi.nlm.nih.gov/pubmed/17354029
But, experts are aware: the real step breaking barriers had not been performed so far. Additionally, it is very important in trying to evaluate and / predict response, that not different tumor entities with different survival and tumor biology are mixed together. Those data are from my perspective not helpful, but maybe that is my own Bias (!) of my view.
INCORE, the International Consortium of Research Excellence of the Theodor-Billroth-Academy, was invited publishing the Editorial in Future Oncology 2012. The consortium pointed out, that living within an area of ‘prove of principle’ and also trying to work out level of evidence in medicine, it is “the duty and responsibility” of every clinician, but also of the societies and institutions, also of the WHO.
Complete remission is not the only goal, as experts dealing with ‘response-research’ are aware. It is so frustrating for patients and clinicians: there is a rate of those patients with complete remission, who develop early recurrence ! This reflects, that complete remission cannot function as the only criterion describing response !
Again, my heartly thanks, that Dr. Sanexa discussed this issue in detail.
I hope, I found the way explaining the way of development and evaluating response criteria properly and in a differentiated way of view. From the perspective of INCORE:
“an interdisciplinary initiative with all key stake¬holders and disciplines represented is imperative to make predictive and prognostic individualized tumor response assessment a modern-day reality. The integrated multidisciplinary panel of international experts need to define how to leverage existing data, tissue and testing platforms in order to predict individual patient treatment response and prognosis.”
- edit this on December 5, 2012 at 5:34 AM | Reply ritusaxena
Dr. Brucher,
First of all thanks for expressing your views on the ‘tumor response’ in a comprehensive way. You are the first author of the editorial review one of the prominent people who has taken part in the process of defining tumor response and I am glad that you decided to write a comment on the writeup.
The topic has been explained well in an immaculate manner and that it further clarifies the need for the perfect markers that would be able to evaluate and predict tumor response. There are, as you mentioned, some molecular markers available including VEGF, cyclins, that have been brought to focus in the context of squamous cell carcinoma.
It would be great if you could be the guest author for our blog and we could publish your opinion (comment on this blog post) as a separate post. Please let us know if it is OK with you.
Thanks again for your comment
Ritu
Thank you all to the compelling discussions, above.
Please review the two sources on the topic I placed at the bottom of the post, above as post on this Scientific Journal,
All comments made to both entries are part of this discussion, I am referring to Dr. Nir’s post on size of tumor, to BB comment to Nir’s post, to Larry’ Pathologist view on Tumors and my post on remission and minimally invasive surgery (MIS).
Great comments by Dr. Williams, BB and wonderful topic exposition by Dr. Ritu.
- edit this on December 5, 2012 at 6:43 AM | Replyritusaxena
Aviva,
Thats a great idea. I will combine all sources referred by you, the post on tumor imaging by Dr. Nir and the comments made on the these posts including Dr. Brucher’s comments in a new posts.
Thanks
Ritu
Great idea, ask Larry, he has written two very long important comments on this topic, one on Nir’s post and another one, ask him where, if it is not on MIS post. GREAT work, Ritu, integration is very important. Dr, Williams is one of our Gems.
Assessing tumour response it is not an easy task! Because tumours don’t change, but happilly our knowlege (about them) does really change, is ever changing (thank god!). In the past we had the Recist Criteria, then the Modified Recist Criteria, because of Gist and other tumors. At this very moment, these are clearly insuficient. We do need more, new validated facing the reality of nowadays. A great enormous post Dr Ritu! Congratulations!
See also Multiple Comment Exchanges submitted for:
· Knowing the tumor’s size and location, could we target treatment to THE ROI by applying…..
Author: Dror Nir, PhD
See also Multiple Comment Exchanges submitted for:
- Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?
Author: Larry H. Bernstein, MD, FCAP
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Curator: Aviva Lev-Ari, PhD, RN
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All scientific papers to be free by 2020 under EU proposals
Reporter: Aviva Lev-Ari, PhD, RN
· SAME SCIENTIFIC IMPACT: Scientific Publishing – Open Journals vs. Subscription-based
Reporters: Aviva Lev-Ari, PhD, RN & Pnina G. Abir-Am, PhD
· June 19, 2016 – We Celebrate reaching over One Million e-Readers @PharmaceuticalIntelligence.com
Editor-in-Chief: Aviva Lev-Ari, PhD, RN
· By Design: A BRANDING Engine “Hard-wired” in the Ontology of an Open Access Online Scientific Journal @ Leaders in Pharmaceutical Business Intelligence (LPBI)
Author and Platform’s Features Designer: Aviva Lev-Ari, PhD, RN
· Elsevier’s Mendeley and Academia.edu – How We Distribute Scientific Research: A Case in Advocacy for Open Access Journals
Curator and Reporter: Aviva Lev-Ari, PhD, RN
· Reconstructed Science Communication for Open Access Online Scientific Curation
Author and Curator: Larry H Bernstein, MD, FCAP and Co-Curator: Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2014/01/04/reconstructed-science-communication-for-curation/
· e-Recognition via Friction-free Collaboration over the Internet: “Open Access to Curation of Scientific Research”
Curator: Aviva Lev-Ari, PhD, RN
· Open-Access Publishing in Genomics
Reporter: Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2013/01/14/open-access-publishing-in-genomics/
· “Open Access Publishing” is becoming the mainstream model: “Academic Publishing” has changed Irrevocably
Reporter: Aviva Lev-Ari, PhD, RN
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http://pharmaceuticalintelligence.com – Nomination submission of the Journal for 2016 Communication Award Excellence in Reporting in Science, Medicine and Engineering, National Academies 2016 Communication Awards
https://www.linkedin.com/pulse/httppharmaceuticalintelligencecom-nomination-2016-lev-ari-phd-rn/
F3 Selection of electronic Books vs Hardcover or Softcover type of product
· Digital Publishing Promotes Science and Popularizes it by Access to Scientific Discourse
Curator & Reporter: Aviva Lev-Ari, PhD, RN
· Nomination: National Academies 2016 Communication Awards – EXCELLENCE in REPORTING SCIENCE and MEDICINE: BioMed e-Series, 2015 publications by LPBI
https://www.linkedin.com/pulse/nomination-national-academies-2016-communication-lev-ari-phd-rn/
F4 Examples of Creative Article Titles
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We celebrate 5,070 Scientific Articles – pharmaceuticalintelligence.com – Top Posts with Greater than 2,000 Views
Editor-in-Chief: Aviva Lev-Ari, PhD, RN
· Calcium and Cardiovascular Diseases: A Series of Twelve Articles in Advanced Cardiology
Curator: Aviva Lev-Ari, PhD, RN
Part I:
Identification of Biomarkers that are Related to the Actin Cytoskeleton
Larry H Bernstein, MD, FCAP
Part II:
Role of Calcium, the Actin Skeleton, and Lipid Structures in Signaling and Cell Motility
Larry H. Bernstein, MD, FCAP, Stephen Williams, PhD and Aviva Lev-Ari, PhD, RN
Part III:
Renal Distal Tubular Ca2+ Exchange Mechanism in Health and Disease
Larry H. Bernstein, MD, FCAP, Stephen J. Williams, PhD and Aviva Lev-Ari, PhD, RN
Part IV:
Larry H Bernstein, MD, FCAP, Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
Part V:
Larry H Bernstein, MD, FCAP, Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN
Part VI:
Aviva Lev-Ari, PhD, RN
Part VII:
Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Part VIII
Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Part IX
Justin Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Part X
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Part XI
Sensors and Signaling in Oxidative Stress – Part XI
Larry H. Bernstein, MD, FCAP
Part XII
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD,
Part XIII
Ca2+-Stimulated Exocytosis: The Role of Calmodulin and Protein Kinase C in Ca2+ Regulation of Hormone and Neurotransmitter
Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
F5 Examples of Creative eTOCs
Series C: e-Books on Cancer & Oncology
- Volume 1: Cancer Biology & Genomics for Disease Diagnosis. On comsince 8/11/2015
http://www.amazon.com/dp/B013RVYR2K
- Volume 2: Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery(Series C Book 2). On com since 5/18/2017
http://www.amazon.com/dp/B071VQ6YYK
Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases
- Metabolomics
VOLUME 1: Metabolic Genomics and Pharmaceutics. On Amazon.com since 7/21/2015
http://www.amazon.com/dp/B012BB0ZF0
- The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications
VOLUME 2: Infectious Diseases and Therapeutics
VOLUME 3: The Immune System and Therapeutics
(Series D: BioMedicine & Immunology) Kindle Edition. On Amazon.com since September 4, 2017
https://www.amazon.com/dp/B075CXHY1B
F6 Examples of Hierarchical Ontologies created by Experts/Authors/Writers for selected Categories of Research with +500 Articles
- 960 articles on Cancer Biology & Innovations in Cancer Therapy
- 739 articles on Frontiers in Cardiology and Cardiovascular Disorders
- 636 articles on Personalized and Precision Medicine & Genomics Research
- 595 articles on Cell Biology and Cell Circuits
Go to https://pharmaceuticalintelligence.com/
- Click on Select Category on the right hand side of the Home Page
- Click on one of the Categories below to observe the Hierarchical Ontologies
- Click on the Parent or a subsequent sub-category to fetch all the articles nested
F7 Articles of Note on selective Research Topic @PharmaceuticalIntelligence
· Articles on Cancer-Related Topic in http://pharmaceuticalintelligence.com Scientific Journal
Curator: Stephen J Williams, PhD
· Articles on Minimally Invasive Surgery (MIS) in Cardiovascular Diseases by the Team @Leaders in Pharmaceutical Business Intelligence (LPBI) Group
https://www.linkedin.com/pulse/articles-minimally-invasive-surgery-mis-diseases-team-aviva/
· Proteomics, Metabolomics, Signaling Pathways, and Cell Regulation – Articles of Note, LPBI Group’s Scientists @ http://pharmaceuticalintelligence.com
https://www.linkedin.com/pulse/proteomics-metabolomics-signaling-pathways-cell-lev-ari-phd-rn/
· Articles of Note on Signaling and Metabolic Pathways published by the Team of LPBI Group in @pharmaceuticalintelligence.com
https://www.linkedin.com/pulse/articles-note-signaling-metabolic-pathways-published-aviva/
· Pancreatic Cancer: Articles of Note @PharmaceuticalIntelligence.com
https://www.linkedin.com/pulse/pancreatic-cancer-articles-note-aviva-lev-ari-phd-rn/
· Immune System Stimulants: Articles of Note @pharmaceuticalintelligence.com
https://www.linkedin.com/pulse/immune-system-stimulants-articles-note-aviva-lev-ari-phd-rn/
· Alzheimer’s Disease: Novel Therapeutical Approaches — Articles of Note @PharmaceuticalIntelligence.com
https://www.linkedin.com/pulse/alzheimers-disease-novel-therapeutical-approaches-lev-ari-phd-rn/
· Prostate Cancer: Diagnosis and Novel Treatment – Articles of Note @PharmaceuticalIntelligence.com
https://www.linkedin.com/pulse/prostate-cancer-diagnosis-novel-treatment-articles-lev-ari-phd-rn/
· Nutrition: Articles of Note @PharmaceuticalIntelligence.com
https://www.linkedin.com/pulse/nutrition-articles-note-pharmaceuticalintelligencecom-aviva/
· Epigenetics, Environment and Cancer: Articles of Note @PharmaceuticalIntelligence.com
https://www.linkedin.com/pulse/epigenetics-environment-cancer-articles-note-aviva-lev-ari-phd-rn/
· Contributions to Personalized and Precision Medicine & Genomic Research
https://www.linkedin.com/pulse/contributions-personalized-precision-medicine-genomic-aviva/
G. Editor-in-Chief’s Roles and Accomplishments
G1 Curation Methodology Development
In Section F1, above we present the Leadership we provide on curation of scientific findings in the eScientific publishing for Medical Education contents.
In Section G1, the Leadership we provide on curation of scientific findings in the eScientific publishing for Medical Education contents is demonstrated by a subset of several outstanding curations with high electronic Viewer volume. Each article included presents unique content contribution to Medical Clinical Education.
· These articles are extracted from the list of all Journal articles with >1,000 eReaders, 4/28/2012 to 1/29/2018.
Article Title, # of electronic Viewers, Author(s) Name
| Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View? | 16,114 | Larry H. Bernstein, MD, FCAP |
| Do Novel Anticoagulants Affect the PT/INR? The Cases of XARELTO (rivaroxaban) and PRADAXA (dabigatran) | 11,606 | Vivek Lal, MBBS, MD, FCIR,
Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN |
|||||
| Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care
|
5,865 | Aviva Lev-Ari, PhD, RN | |||||
| Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes | 1,919 | Aviva Lev-Ari, PhD, RN | |||||
| Bystolic’s generic Nebivolol – Positive Effect on circulating Endothelial Progenitor Cells Endogenous Augmentation | 1,059 | Aviva Lev-Ari, PhD, RN |
| Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes | 1,339 | Aviva Lev-Ari, PhD, RN |
G2 Content Creation and Key Opinion Leader (KOL) Recognition
G2.1 Volume of Articles in the Journal and in the 16 Volume-BioMed e-Series
| Select
Aviva Lev-Ari, PhD, RN 2012pharmaceutical |
3,064 Articles |
avivalev-ari@alum.berkeley.edu | Administrator | 3064 |
G2.1 Volume of Articles in the Journal and in the 16 Volume-BioMed e-Series
1. Volume of Articles in the Journal since Journal inception on 4/28/2012:
- Total articles by ALL authors in Journal Archive on 1/29/2018 = 5,288
- ALL articles/posts Authored, Curated, Reported by Aviva Lev-Ari, PhD, RN = 3,064
2. Volume of Articles in the 16 Volume-BioMed e-Series
- Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Aviva Lev-Ari, PhD, RN
- 557 Co-Curations, Single Author Curations and Scientific Reports in 13 Volumes of LPBI’s BioMed e-Series by Aviva Lev-Ari, PhD, RN
https://www.linkedin.com/pulse/557-co-curations-single-author-curation-scientific-13-aviva/
3. Biography and Bibliographies: LPBI Group’s Founder – Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/founder/
- Reflections on a Four-phase Career: Aviva Lev-Ari, PhD, RN, March 2018
G2.2 Digital Presence measured by eViews: Clicks on article by Author Name
Top Authors for all days ending 2018-01-29 (Summarized) – All Time
| Author Name | electronic Views | |
| Aviva Lev-Ari, PhD, RN [2012pharmaceutical] | 352,153 |
| Our TEAM | Clicks on Tab
5,934 |
|
||||
| Founder | 3,257 | |||||
| BioMed e-Series | 3,140 | |||||
| Journal PharmaceuticalIntelligence.com – 2,214 | 2,214 | ||||||
| About – 2,054 | 2,054 | ||||||
| VISION – 2,803 | 2,803 | ||||||
|
1,201 | ||||||
G2.3 Digital KOL Parameters
Key Opinion Leader (KOL) – Aviva Lev-Ari, PhD, RN, as Evidenced by
G3 Team building: Editors and Expert, Authors, Writers
Our Team
- Aviva Lev-Ari, PhD, RN, Director and Founder
- Members of the Board
- Senior Editors
- Experts, Authors, Writers (EAWs)
- Business Development & Private Equity Investment
- Scientific Delegation Members & Patent Holders
- Inventors: Biologics
- Inventors: Medical Devices
- Research Associates
Selection of Journal’s Chief Scientific Officer (CSO) and BioMed e-Series Content Consultant (CC): Series B, C, D, E
L. H. Bernstein, MD, FCAP
Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Larry H Bernstein, MD, FCAP
G4 Book Title Generation and Cover Page Design
As BioMed e-Series Editor–in-Chief, was responsible for the following functions of product design and product launch
· 16 Title creations for e-Books
· Designed 16 Cover Pages for a 16-Volume e-Books e-Series in BioMed
· Designed Series A, eTOCs for SIX Volumes and
· Approved of all 16 electronic Table of Contents (eTOCs), working in tandem with all the Editors of each volume and all the Author contributors of article contents in the Journal.
· Commissioned Articles by Authors/Curators per Author’s expertise on a daily basis
Below, see Volume Titles and Cover Pages:
13 LIVE results for Kindle Store: “Aviva Lev-Ari
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Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics
Nov 28, 2015 | Kindle eBook
by Justin D. Pearlman MD ME PhD MA FACC and Stephen J. Williams PhDSold by: Amazon Digital Services LLC -
Amazon’s Aviva Lev-Ari Page
Discover books, read about the author, find related products, and more.More about Aviva Lev-Ari -
Perspectives on Nitric Oxide in Disease Mechanisms (Biomed e-Books Book 1)
Jun 20, 2013 | Kindle eBook
by Margaret Baker PhD and Tilda Barliya PhDSold by: Amazon Digital Services LLC -
The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications: VOLUME 2: Infectious Diseases and Therapeutics and VOLUME 3: The … (Series D: BioMedicine & Immunology)
Sep 4, 2017 | Kindle eBook
by Larry H. Bernstein and Aviva Lev-AriSold by: Amazon Digital Services LLC -
The VOICES of Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures … E: Patient-Centered Medicine Book 1)
Oct 16, 2017 | Kindle eBook
by Larry H. Bernstein and Aviva Lev-AriSold by: Amazon Digital Services LLC -
Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation: The Art of Scientific & Medical Curation
Nov 29, 2015 | Kindle eBook
by Larry H. Bernstein MD FCAP and Aviva Lev-Ari PhD RNSold by: Amazon Digital Services LLC -
Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics (Series E: Patient-Centered Medicine Book 3)
Dec 26, 2015 | Kindle eBook
by Larry H. Bernstein MD FACP and Aviva Lev-Ari PhD RNSold by: Amazon Digital Services LLC -
Cancer Biology and Genomics for Disease Diagnosis (Series C: e-Books on Cancer & Oncology Book 1)
Aug 10, 2015 | Kindle eBook
by Larry H Bernstein MD FCAP and Prabodh Kumar Kandala PhDSold by: Amazon Digital Services LLC -
Medical 3D BioPrinting – The Revolution in Medicine Technologies for Patient-centered Medicine: From R&D in Biologics to New Medical Devices (Series E: Patient-Centered Medicine Book 4)
Dec 30, 2017 | Kindle eBook
by Larry H. Bernstein and Irina RobuSold by: Amazon Digital Services LLC -
Metabolic Genomics & Pharmaceutics (BioMedicine – Metabolomics, Immunology, Infectious Diseases Book 1)
Jul 21, 2015 | Kindle eBook
by Larry H. Bernstein MD FCAP and Prabodah Kandala PhDSold by: Amazon Digital Services LLC -
Regenerative and Translational Medicine: The Therapeutic Promise for Cardiovascular Diseases
Dec 26, 2015 | Kindle eBook
by Justin D. Pearlman MD ME PhD MA FACC and Ritu Saxena PhDSold by: Amazon Digital Services LLC -
Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders (Series E)
Dec 9, 2017 | Kindle eBook
by Larry H. Bernstein and Aviva Lev-AriSold by: Amazon Digital Services LLC -
Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery (Series C Book 2)
May 13, 2017 | Kindle eBook
by Larry H. Bernstein and Demet SagSold by: Amazon Digital Services LLC -
Genomics Orientations for Personalized Medicine (Frontiers in Genomics Research Book 1)
Nov 22, 2015 | Kindle eBook
by Sudipta Saha PhD and Ritu Saxena PhDSold by: Amazon Digital Services LLC
G5 Style Setting: Instruction manuals for Journal, Articles, Books
As BioMed e-Series Editor–in-Chief, Aviva Lev-Ari, PhD, RN was responsible for
· All the documentation (Instruction manuals) on Style setting, and for
· Training all team members
· Journal Articles Format
· Journal Comment Exchange Format
· e-Books Production Process:
1. Volume creation from Journal’s Article Archive,
2. Format Translation from HTML to .mobi for Kindle devices,
3. Proof reading process,
4. Title release,
5. Book electronic Upload to Amazon.com Cloud.
6. Connection of all articles and e-Books to Social Media, Ping back generation by mentioning other related articles published in the Journal
Lastly, G6, below
G6 Annual Workflow Management of Multiple eTOCs – Multi-year Book Publishing Scheduling Plan, 2013 – Present
| Title | Date of Publication | Number of Pages |
| Perspectives on Nitric Oxide in Disease Mechanisms | 6/21/2013 | 895 |
| Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation | 11/30/2015 | 11039 KB |
| Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics | 11/29/2015 | 12333 KB |
| Regenerative and Translational Medicine: The Therapeutics Promise for Cardiovascular Diseases | 12/26/2015 | 11668 KB |
| Genomics Orientations for Personalized Medicine | 11/23/2015 | 11724 KB |
| Cancer Biology & Genomics for Disease Diagnosis | 8/11/2015 | 13744 KB |
| Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery | 5/18/2017 | 5408 pages |
| Metabolic Genomics and Pharmaceutics | 7/21/2015 | 13927 KB |
| The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications | 9/4/2017 | 3747 pages |
| The VOICES of Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures | 10/16/2017 | 826 pages |
| Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders | 12/9/2017 | 2862 pages |
| Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics | 12/27/2015 | 11125 KB |
| Medical 3D BioPrinting – The Revolution in Medicine, Technologies for Patient-centered Medicine: From R&D in Biologics to New Medical Devices | 12/30/2017 | 1005 pages |
|
Pharmacological Agents in Treatment of Cardiovascular Disease
|
12/23/2018 | 185 – no format conversion to MS Word, e-book contains links, Clinical Pearls and Editorials |
|
Interventional Cardiology for Disease Diagnosis and Cardiac Surgery for Condition Treatment |
12/24/2018
|
169 – – no format conversion to MS Word, e-book contains links, Clinical Pearls and Editorials |
| Series B, Volume 1:
Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology |
Work-in-Progress, Expected Publishing date in 2019 | ??? |
2012pharmaceutical
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Alan F. Kaul, PharmD., MS, MBA, FCCP
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