Archive for the ‘Personalized and Precision Medicine & Genomic Research’ Category

CRISPR-Cas9 Discovery and Development of Programmable Genome Engineering – Gabbay Award Lectures in Biotechnology and Medicine – Hosted by Rosenstiel Basic Medical Sciences Research Center, 10/27/14 3:30PM Brandeis University, Gerstenzang 121

Posted in Academic Publishing, Conference Coverage with Social Media, Gene Regulation, Gene Regulation and Evolution, Genetics & Pharmaceutical, Genomic Testing: Methodology for Diagnosis, Genomics Pharmacy, Immunodiagnostics, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, Innovation in Immunology Diagnostics, Intellectual Property, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, Interviews with Scientific Leaders, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Proteomics, RNA Biology, RNA Biology, Cancer and Therapeutics, Scientific & Biotech Conferences: Press Coverage on October 26, 2014| Leave a Comment »

LIVE – Now –>> CRISPR-Cas9 Discovery and Development of Programmable Genome Engineering – Gabbay Award Lectures in Biotechnology and Medicine – Hosted by Rosenstiel Basic Medical Sciences Research Center, 10/27/14 3:30PM Brandeis University, Gerstenzang 121

Reporter: Aviva Lev-Ari, PhD, RN

Article ID #157: Article ID #159: CRISPR-Cas9 Discovery and Development of Programmable Genome Engineering – Gabbay Award Lectures in Biotechnology and Medicine – Hosted by Rosenstiel Basic Medical Sciences Research Center, 10/27/14 3:30PM Brandeis University, Gerstenzang 121. Published on 10/26/2014

WordCloud Image Produced by Adam Tubman

REAL TIME Conference Coverage by Dr. Aviva Lev-Ari, PhD, RN

For more Biotech Conferences Covered in Real Time by Dr. Aviva Lev-Ari, PhD, RN for Leaders in Pharmaceutical Business Intelligence using Social Media and Open Access Online Scientific Journal http://pharmaceuticalintelligence.com

click on

http://pharmaceuticalintelligence.com/press-coverage/

For articles on CRISPR-Cas9 in Open Access Online Scientific Journal http://pharmaceuticalintelligence.com

click on

http://pharmaceuticalintelligence.com/?s=CRISPR-Cas9

LIVE CONTENT from

Gabbay Award Lecture in Biotechnology and Medicine @Brandeis

is been added 0n 10/27 @3;30PM

InVivo Target Search Mechanism – Fast Cas9 Diffusion in Live Cells

First Speaker

Emmanuelle Charpentier (Dept. of Molecular Biology. Umea University; Dept. of Regulation in Infection Biology, Helmholtz Centre for Infection Research)

CRISPR-Cas9: How a Bacterial Immune System Revolutionizes Life Sciences and Medicine

application in dairy industry basilicum, bacteria

Second Speaker

Jennifer Doudna (Dept. of Biochemistry, Biophysics and Structural Biology, UC Berkeley)CRISPR-Cas9 Discovery and Development of Programmable Genome Engineering

Bacterial/archaeal chromosome

a single gene CAs9m- enzyme single-guide RNAs (sgRNAs)

crRNA

A Programmable Dual-RNA- Genome editing begins with dsDNA cleavange

ZFHs, TALENs, HEs, Cas9:sgRNA

protein DNA recognition

Genome targeting technologies: ZFN & TALEN

/Cas9/targeting RNA bound by a nuclease

2012-RNA-guided DNA endonuclease

1/2013 Church, Zhang

Re-Writing the Genome:

DNA structu

restriction enzymes

PCR

Specific genome editing in cell and in organizmism

robust transcriptional control with ccatalyrtic

In the Lab @Berkeley

Hoe Cas9 find DNA targets with high specificity

Mechanism of DNA interrogation

high affinity product binding, no substrate turnover
binding first occur at PAM motifs
PAM binding triggers Cas9 catalytic activity

CRISPR: Clusters of Regulary

three steps to acquire immunity in bacteria

1. adaptation

2. crRNA biogenesis

3. Interference

CRISPR in Structural Biology

RNA-induced conversion of Cas9 into an active confrontation – crystal structure morphology

Models for DNA interrogation by Cas9:RNA

Programmed RNA cleavage using Cas9:gRNA in O’Connell at al. (2014) Nature

Therapeutic Applications

1. Delivery of antibiotic small molecule

2. Animal models live cell (catalitic inactive version vs active version)

Third Speaker

Feng Zhang (McGovern Inst. for Brain Research, MIT)
Development and Applications of CRISPR-Cas9 for Genome Editing

Brain Research – Applications for CRISPER

Genetics & epigenetics
signals – optogenetics Neuromodulation
optogenetics — fibers — cells

The CRISPR/Cas bacterial

Crispr RNA maturation

E.coli – immunity for using Crispr

Streptococcus thermophilus – CRISPr editing applied

Development of a Technology Platform

expand modes of Genomic Pertubation

develop efficient co-transduction of primary neurons

multiplex knockout un the denate

demonstrate uses in biological therapeutic context

CRISPR — Reagents development, protocol developed, discussion forums

targeting of MeCP2 gyrus leads to robust protein depletion and behavior change

toxicity potential researched

Cre-dedendent CAs9 MOUSE FOR CANCER MODELING – mouth lung

develop an open source for the community

Genome-scale CRISPR knockout (GeCKO) Screen – generate library pool of cell – mutation identification – melanoma treated by BRAF inhibitor – targets for menanoma resistence

Comparison of shRNA vs GeCKO – CRISPR more robust and statisticaly significant, However, GeCKO provides higher sensitivity than shRNA

foundational technology development

Crystal structure of Cas9 in complex wiht guided RNA and target DNA

Cre-dependent Cas9 Mouse

For Twitter.com

#Cas9
#CRISPR
#molecularbiology
#biotechnology
#GeneEditing
#genetic#engineering (sometimes these two # are put together like this)
#Boston

@BrandeisU
@MIT
@UCBerkeley
@CRISPRpapers
@UmeaUniversity
@mcgovernmit (this is for Feng Zhang)
@pharma_BI

CRISPR Service / Cas9

Commercialization by

http://www.appliedstemcell.com/services/cell-line-models/cell-line-modification/

The CRISPR/Cas9 system uses the Cas9 nuclease to facilitate RNA-guided site-specific DNA cleavage. The system consists of two components:

(1) Mammalian codon-optimized version of the Cas9 protein carrying a nuclear localization signal to ensure nuclear compartmentalization in mammalian cells

(2) Guide RNAs (gRNAs) to direct Cas9 protein to sequence-specifically cleave the targeted DNA

The advantage of CRISPR/Cas9 over ZFNs or TALENs is its scalability and multiplexibility in that multiple sites within the mammalian genome can be simultaneously modified, providing a robust, high-throughput approach for gene editing in mammalian cells.

CRISPR Service (Point mutation, Deletion, Small DNA insertion)

We are experts in CRISPR Service! Applied StemCell is in Nature Biotechnology as one of the select companies for CRISPR-Cas9 tools! Monya Baker, “Gene Editing at CRISPR Speed,” Nature Biotechnology, 32: 309-312, April 2014.

Since Applied Stem Cell started out as a company focused on induced pluripotent stem cells (iPSCs), we have excellent capabilities of correcting mutations in disease-model iPSCs using CRISPR/ Cas9.

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Geneticist George Church: A Future Without Limits

Posted in BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, BioTechnology - Venture Creation, Genomic Testing: Methodology for Diagnosis, Interviews with Key Opinion Leaders (KOLs), Investment in Technological Breakthrough, Massachusetts Academy of Sciences (MAS) , Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Personalized Medicine Coalition, Precision Cancer Medicine, RNA Biology, Cancer and Therapeutics, Scoop.it, Transcriptomics, Translational Science, tagged biotech, Exome sequencing, gene, George Church, MIT, Personalized medicine, precision medicine, variants, Venture capital, WES on October 24, 2014| Leave a Comment »

Geneticist George Church: A Future Without Limits

Reporter: Aviva Lev-Ari, PhD, RN

WordCloud Image Produced by Adam Tubman

UPDATED 12/05/2020

In the future, George Church believes, almost everything will be better because of genetics. If you have a medical problem, your doctor will be able to customize a treatment based on your specific DNA pattern. When you fill up your car, you won’t be draining the world’s dwindling supply of crude oil, because the fuel will come from microbes that have been genetically altered to produce biofuel. When you visit the zoo, you’ll be able to take your children to the woolly mammoth or passenger pigeon exhibits, because these animals will no longer be extinct. You’ll be able to do these things, that is, if the future turns out the way Church envisions it—and he’s doing everything he can to see that it does.

UPDATED 12/05/2020

George Church backs a startup solution to the massive gene therapy manufacturing bottleneck

Source: https://endpts.com/george-church-backs-a-startup-solution-to-the-massive-gene-therapy-manufacturing-bottleneck/
Jason Mast: Associate Editor
George Church and his graduate students have spent the last decade seeding startups on the razor’s edge between biology and science fiction: gene therapy to prevent aging, CRISPRed pigs that can be used to harvest organs for transplant, and home kits to test your poop for healthy or unhealthy bacteria. (OK, maybe they’re not all on that razor’s edge.)

But now a new spinout from the Department of Genetics’ second floor is tackling a far humbler problem — one that major company after major company has stumbled over as they tried to get cures for rare diseases and other gene therapies into the clinic and past regulators: How the hell do you build these?

CEO Lex Vovner of 64x Bio

“There’s a lot happening for new therapies but not enough attention around this problem,” Lex Rovner, who was a post-doc at Church’s lab from 2015 to 2018, told Endpoints News. “And if we don’t figure out how to fix this, many of these therapies won’t even reach patients.”

This week, with Church and a couple other prominent scientists as co-founders, Rovner launched 64x Bio to tackle one key part of the manufacturing bottleneck. They won’t be looking to retrofit plants or build gene therapy factories, as Big Pharma and big biotech are now spending billions to do. Instead, with $4.5 million in seed cash, they will try to engineer the individual cells that churn out a critical component of the therapies.

George Church
The goal is to build cells that are fine-tuned to do nothing but spit out the viral vectors that researchers and drug developers use to shuttle gene therapies into the body. Different vectors have different demands; 64x Bio will look to make efficient cellular factories for each.

“While a few general ways to increase vector production may exist, each unique vector serotype and payload poses a specific challenge,” Church said in an emailed statement. “Our platform enables us to fine tune custom solutions for these distinct combinations that are particularly hard to overcome.”

Before joining Church’s lab, Rovner did her graduate work at Yale, where she studied how to engineer bacteria to produce new kinds of protein for drugs or other purposes. And after leaving Church’s lab in 2018, she initially set out to build a manufacturing startup with a broad focus.

Yet as she spoke with hundreds of biotech executives on LinkedIn and in coffee shops around Cambridge, the same issue kept popping up: They liked their gene therapy technology in the lab but they didn’t know how to scale it up.

“Everyone kept saying the same thing,” Rovner said. “We basically realized there’s this huge problem.”

The issue would soon make headlines in industry publications: bluebird delaying the launch of Zynteglo, Novartis delaying the launch of Zolgensma in the EU, Axovant delaying the start of their Parkinson’s trial.

Part of the problem, Rovner said, is that gene therapies are delivered on viral vectors. You can build these vectors in mammalian cell lines by feeding them a small circular strand of DNA called a plasmid. The problem is that mammalian cells have, over billions of years, evolved tools and defenses precisely to avoid making viruses. (Lest the mammal they live in die of infection).

There are genetic mutations that can turn off some of the internal defenses and unleash a cell’s ability to produce virus, but they’re rare and hard to find. Other platforms, Rovner said, try to find these mutations by using CRISPR to knock out genes in different cells and then screening each of them individually, a process that can require hundreds of thousands of different 100-well plates, with each well containing a different group of mutant cells.

“It’s just not practical, and so these platforms never find the cells,” Rovner said.

64x Bio will try to find them by building a library of millions of mutant mammalian cells and then using a molecular “barcoding” technique to screen those cells in a single pool. The technique, Rovner said, lets them trace how much vector any given cell produces, allowing researchers to quickly identify super-producing cells and their mutations.

The technology was developed partially in-house but draws from IP at Harvard and the Wyss Institute. Harvard’s Pam Silver and Wyss’s Jeffrey Way are co-founders.

The company is now based in SoMa in San Francisco. With the seed cash from Fifty Years, Refactor and First Round Capital, Rovner is recruiting and looking to raise a Series A soon. They’re in talks with pharma and biotech partners, while they try to validate the first preclinical and clinical applications.

Gene therapy is one focus, but Rovner said the platform works for anything that involves viral vector, including vaccines and oncolytic viruses. You just have to find the right mutation.

“It’s the rare cell you’re looking for,” she said.

AUTHOR
Jason Mast
Associate Editor
jason@endpointsnews.com
@JasonMMast
Jason Mas

In 2005 he launched the Personal Genome Project, with the goal of sequencing and sharing the DNA of 100,000 volunteers. With an open-source database of that size, he believes, researchers everywhere will be able to meaningfully pursue the critical task of correlating genetic patterns with physical traits, illnesses, and exposure to environmental factors to find new cures for diseases and to gain basic insights into what makes each of us the way we are. Church, tagged as subject hu43860C, was first in line for testing. Since then, more than 13,000 people in the U.S., Canada, and the U.K. have volunteered to join him, helping to establish what he playfully calls the Facebook of DNA.

Church has made a career of defying the impossible. Propelled by the dizzying speed of technological advancement since then, the Personal Genome Project is just one of Church’s many attempts to overcome obstacles standing between him and the future.

“It’s not for everyone,” he says. “But I see a trend here. Openness has changed since many of us were young. People didn’t use to talk about sexuality or cancer in polite society. This is the Facebook generation.” If individuals were told which diseases or medical conditions they were genetically predisposed to, they could adjust their behavior accordingly, he reasoned. Although universal testing still isn’t practical today, the cost of sequencing an individual genome has dropped dramatically in recent years, from about $7 million in 2007 to as little as $1,000 today.

“It’s all too easy to dismiss the future,” he says. “People confuse what’s impossible today with what’s impossible tomorrow.”, especially through the emerging discipline of “synthetic” biology. The basic idea behind synthetic biology, he explained, was that natural organisms could be reprogrammed to do things they wouldn’t normally do, things that might be useful to people. In pursuit of this, researchers had learned not only how to read the genetic code of organisms but also how to write new code and insert it into organisms. Besides making plastic, microbes altered in this way had produced carpet fibers, treated wastewater, generated electricity, manufactured jet fuel, created hemoglobin, and fabricated new drugs. But this was only the tip of the iceberg, Church wrote. The same technique could also be used on people.

“Every cell in our body, whether it’s a bacterial cell or a human cell, has a genome,” he says. “You can extract that genome—it’s kind of like a linear tape—and you can read it by a variety of methods. Similarly, like a string of letters that you can read, you can also change it. You can write, you can edit it, and then you can put it back in the cell.”

This April, the Broad Institute, where Church holds a faculty appointment, was awarded a patent for a new method of genome editing called CRISPR (clustered regularly interspersed short palindromic repeats), which Church says is one of the most effective tools ever developed for synthetic biology. By studying the way that certain bacteria defend themselves against viruses, researchers figured out how to precisely cut DNA at any location on the genome and insert new material there to alter its function. Last month, researchers at MIT announced they had used CRISPR to cure mice of a rare liver disease that also afflicts humans. At the same time, researchers at Virginia Tech said they were experimenting on plants with CRISPR to control salt tolerance, improve crop yield, and create resistance to pathogens.

The possibilities for CRISPR technology seem almost limitless, Church says. If researchers have stored a genetic sequence in a computer, they can order a robot to produce a piece of DNA from the data. That piece can then be put into a cell to change the genome. Church believes that CRISPR is so promising that last year he co-founded a genome-editing company, Editas, to develop drugs for currently incurable diseases.

Source: news.nationalgeographic.com

See on Scoop.it – Cardiovascular and vascular imaging

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Glycosaminoglycans, Mucopolysaccharides, L-iduronidase, Enzyme Therapy

Posted in Biochemical pathways, Chemical Biology and its relations to Metabolic Disease, Curation, Disease Biology, Genetics & Pharmaceutical, Genome Biology, Metabolism, Metabolomics, Mutant Gene Expression, Nutrition, Nutrition and Phytochemistry, Personalized and Precision Medicine & Genomic Research, Population Health Management, Translational Science, tagged complex arbohydrates, glycosaminoglycans, l-iduronidase, mucopolysaccharidoses on October 23, 2014| Leave a Comment »

Glycosaminoglycans, Mucopolysaccharides, L-iduronidase, Enzyme Therapy

Author and Curator: Larry H. Bernstein, MD, FCAP

This is a portion of the discussion on carbohydrate metabolism that addresses complex carbohydrates, except for the cytoskeleton, but does involve the lysosomal function and storage diseases.

L-Iduronic acid is the major uronic acid component of the glycosaminoglycans dermatan sulfate, and heparin. It is also present in heparan sulfate although here in a minor amount relative to its carbon-5 epimer glucuronic acid.

Complex sugar structures

Carbohydrates form complex structures from glucose, galactose, and other sugars. An amino sugar substitutes an amino group for one of the hydroxyls. An example is glucosamine. The amino group may be acetylated. N-acetylneuraminate, (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Sialic acid imparts a negative charge to glycoproteins because its carboxyl group tends to dissociate a proton at physiological pH.

Glycosidic bonds: The anomeric hydroxyl group and a hydroxyl group of another sugar or some other compound can join together, splitting out water to form a glycosidic bond.

R-OH + HO-R’ –> R-O-R’ + H2O

For example, methanol reacts with the anomeric hydroxyl on glucose to form methyl glucoside (methyl-glucopyranose).

Plants store glucose as amylose or amylopectin, glucose polymers collectively called starch. Glucose storage in polymeric form minimizes osmotic effects. The end of the polysaccharide with an anomeric carbon (C1) that is not involved in a glycosidic bond is called the reducing end.

Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin. But glycogen has more α(1,6) branches. The highly branched structure permits rapid release of glucose from glycogen stores, e.g., in muscle cells during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants.

Glycosaminoglycans (mucopolysaccharides) are linear polymers of repeating disaccharides (diagrams p. 368-369). The constituent monosaccharides tend to be modified, with acidic groups, amino groups, sulfated hydroxyl and amino groups, etc. Glycosaminoglycans tend to be negatively charged, because of the prevalence of acidic groups.

Hyaluronate (hyaluronan) is a glycosaminoglycan with a repeating disaccharide consisting of two glucose derivatives, glucuronate (glucuronic acid) and N-acetylglucosamine. The glycosidic linkages are β(1,3) and β(1,4). Proteoglycans are glycosaminoglycans that are covalently linked to serine residues of specific core proteins. The glycosaminoglycan chain is synthesized by sequential addition of sugar residues to the core protein.

Some proteoglycans of the extracellular matrix bind non-covalently to hyaluronate via protein domains called link modules. For example:

Multiple copies of the aggrecan proteoglycan associate with hyaluronate in cartilage to form large complexes.
Versican, another proteoglycan, binds hyaluronate in the extracellular matrix of loose connective tissues.

Heparan sulfate is initially synthesized on a membrane-embedded core protein as a polymer of alternating glucuronate and N-acetylglucosamine residues. Later, in segments of the polymer, glucuronate residues may be converted to the sulfated sugar iduronic acid, while N-acetylglucosamine residues may be deacetylated and/or sulfated. Some cell surface heparan sulfate glycosaminoglycans remain covalently linked to core proteins associated with the plasma membrane.

glycosaminoglycans

Heparin, a soluble glycosaminoglycan found in granules of mast cells, has a structure similar to that of heparan sulfates, but is relatively highly sulfated. When released into the blood, it inhibits clot formation by interacting with the protein antithrombin. Heparin has an extended helical conformation. Charge repulsion by the many negatively charged groups may contribute to this conformation.

Proteins involved in signaling and adhesion at the cell surface recognize and bind heparan sulfate chains. For example, binding of some growth factors (small proteins) to cell surface receptors is enhanced by their binding also to heparan sulfates.

Regulated cell surface Sulf enzymes may remove sulfate groups at particular locations on heparan sulfate chains to alter affinity for signal proteins such as growth factors.

Oligosaccharides that are covalently attached to proteins or to membrane lipids may be linear or branched chains. They often include modified sugars, e.g., acetylglucosamine, etc. O-linked oligosaccharide chains of glycoproteins vary in complexity. They link to a protein via a glycosidic bond between a sugar residue and a serine or threonine hydroxyl. They have roles in recognition, interaction. N-acetylglucosamine (abbreviated GlcNAc) is a common O-linked glycosylation of protein serine or threonine residues. Many cellular proteins, including enzymes and transcription factors, are regulated by reversible attachment of GlcNAc. Often attachment of GlcNAc to a protein hydroxyl group alternates with phosphorylation, with these two modifications having opposite regulatory effects (stimulation or inhibition).

Many proteins secreted by cells have attached N-linked oligosaccharide chains. Genetic diseases have been attributed to deficiency of particular enzymes involved in synthesizing or modifying oligosaccharide chains of these glycoproteins. Such diseases, and gene knockout studies in mice, have been used to define pathways of modification of oligosaccharide chains of glycoproteins and glycolipids.

The C-type lectin-like domain is a Ca++-binding carbohydrate recognition domain present in many animal lectins. Recognition and binding of carbohydrate moieties of glycoproteins, glycolipids, and proteoglycans by animal lectins is a factor in cell-cell recognition, adhesion of cells to the extracellular matrix, interaction of cells with chemokines and growth factors, recognition of disease-causing microorganisms, and initiation and control of inflammation.

Synthesis of conformationally locked L-iduronic acid derivatives: direct evidence for a critical role of the skew-boat 2S0 conformer in the activation of antithrombin by heparin.

Das SK1, Mallet JM, Esnault J, Driguez PA, Duchaussoy P, Sizun P, Herault JP, Herbert JM, Petitou M, Sinaÿ P. Chemistry. 2001 Nov 19;7(22):4821-34.

We have used organic synthesis to understand the role of L-iduronic acid conformational flexibility in the activation of antithrombin by heparin. Among known synthetic analogues of the genuine pentasaccharidic sequence representing the antithrombin binding site of heparin, we have selected as a reference compound the methylated anti-factor Xa pentasaccharide 1. We have synthesized three analogues of 1, in which the L-iduronic acid unit is locked in one of three fixed conformations. A covalent two atom bridge between carbon atoms two and five of L-iduronic acid was first introduced to lock the pseudorotational itinerary of the pyranoid ring around the 2S0 form. The locked pentasaccharide 23 showed about the same activity as the reference compound 1 in an antithrombin-mediated anti-Xa assay. These results clearly establish the critical importance of the 2S0 conformation of L-iduronic acid in the activation of antithrombin by heparin. http://www.ncbi.nlm.nih.gov/pubmed/11763451

L-Iduronic acid (IdoA) is the major uronic acid component of the glycosaminoglycans (GAGs) dermatan sulfate, and heparin. It is also present in heparan sulfate although here in a minor amount relative to its carbon-5 epimer glucuronic acid. In 2000, LK Hallak described the importance of this sugar in respiratory syncytial virus infection. Dermatan sulfate and heparan sulfate were the only GAGs containing IdoA, and they were the only ones that inhibited RSV infection in cell culture.

The lysosomal hydrolase a-L-iduronidase (IDUA) is one of the enzymes in the metabolic pathway responsible for the degradation of the glycosaminoglycans heparin sulfate and dermatan sulfate. A genomic subclone and a cDNA clone encoding human IDUA were used to localize IDUA to chromosome 4p16.3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1683689/pdf/ajhg00095-0040.pdf

catalytic pathway for IDUA

http://www.nature.com/nchembio/journal/v9/n11/images/nchembio.1357-F3.jpg

Mucopolysaccharidoses (MPS (I-VI)

Mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases, each of which is produced by an inherited deficiency of an enzyme involved in the degradation of acid mucopolysaccharides, now called glycosaminoglycans (GAGs). These diseases are autosomal recessive, except for mucopolysaccharidosis type II, which is X-linked. People with a mucopolysaccharidosis either do not produce enough of one of
the 11 enzymes required to break down these sugar chains into simpler molecules, or they produce enzymes that do not work properly. Over time, these glycosaminoglycans collect in the cells, blood and connective tissues. In these diseases large amounts of complex sugar molecules accumulate in harmful amounts in the body’s cells.

The mucopolysaccharidoses (MPSs) are a group of rare, inherited lysosomal storage disorders that are clinically characterized by abnormalities in multiple organ systems and reduced life expectancy. The MPSs are heterogeneous, progressive disorders. Patients typically appear normal at birth, but during early childhood they experience the onset of clinical disease, including skeletal, joint, airway and cardiac involvement, hearing and vision impairment, and mental retardation in the severe forms of MPS I, MPS II and MPS VII and all subtypes of MPS III. There are two treatment options for patients with MPS that are directed at the underlying pathophysiology: haematopoietic stem cell transplantation, which is useful for selected patients, and recombinant i.v. enzyme replacement therapy, which is available for MPS I, II and VI. Early diagnosis and treatment can improve patient outcomes and may reduce the disease burden on patients and caregivers. As skeletal and joint abnormalities are characteristic of many patients with MPS, rheumatologists are positioned to recognize the features of the disease and to facilitate early diagnosis and referral.
Overview of the mucopolysaccharidoses. Joseph Muenzer.
Rheumatology 2011; 50 (suppl 5): v4-v12. http://dx.doi,org:/10.1093/rheumatology/ker394
Research funded by the NINDS has shown that viral-delivered gene therapy in animal models of the mucopolysaccharidoses can stop the buildup of storage materials in brain cells and improve learning and memory. Enzyme replacement therapy has proven useful in reducing non-neurological symptoms and pain. In 2006, the FDA approved the drug idursulfase (Elaprase) for the treatment of MPS II (Hunter syndrome). This is the first drug shown to have any benefit for one of the mucopolysaccharidoses.

Another lysosomal storage disease often confused with the mucopolysaccharidoses is mucolipidosis. In this disorder, excessive amounts of fatty materials known as lipids (another principal component of living cells) are stored, in addition to sugars. Persons with mucolipidosis may share some of the clinical features associated with the mucopolysaccharidoses (certain facial features, bony structure abnormalities, and damage to the brain), and increased amounts of the enzymes needed to break down the lipids are found in the blood.

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Introduction to Metabolomics

Posted in Academic Publishing, Anaerobic Glycolysis, Anemia, Biochemical pathways, Biological Networks, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cachexia, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Cerebrovascular and Neurodegenerative Diseases, Computational Biology/Systems and Bioinformatics, Curation, Cytoskeleton, Developmental biology, Diabetes Mellitus, Disease Biology, Endocrine Diseases, Enzyme Induction, Enzymes and isoenzymes, Folate and B12, Gene Regulation, Gene Regulation and Evolution, Genetics & Pharmaceutical, Genomic Expression, Glycobiology: Biopharmaceutical Production, Health Economics and Outcomes Research, Hematopoiesis, Hexokinase, Human Immune System in Health and in Disease, Infectious Disease & New Antibiotic Targets, Intellectual Property, Iron deficiency, Lipid metabolism, Liver & Digestive Diseases Research, Lymphoma, Metabolism, Metabolomics, Methylation, Molecular Genetics & Pharmaceutical, Mutant Gene Expression, Myelodysplasia, Myocardial adenine nucleotide metabolism, Myocardial Ischemia, Myocardial Metabolism, Neurohumoral Transmission, Nitric Oxide in Health and Disease, Nutrition, Nutrition and Phytochemistry, Oxidative phosphorylation, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Discovery, Pharmacodynamics and Pharmacokinetics, Pharmacologic toxicities, Plant extract, Population Health Management, Proteomics, Pyruvate Kinase, Rapid automation of plasma protein pools, RNA Biology, Signaling, Signaling & Cell Circuits, Small Molecules in Development of Therapeutic Drugs, Systemic Inflammatory Response Related Disorders, Technology Transfer: Biotech and Pharmaceutical, Transcriptomics, Translational Science, Warburg effect, tagged carbohyudrate metabolism, metabolic maps, Metabolism, Metabolomics, pharmaceutical targets, Proteomics on October 21, 2014| Leave a Comment »

Introduction to Metabolomics

Author: Larry H. Bernstein, MD, FCAP

This is the first volume of the Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases. It is written for comprehension at the third year medical student level, or as a reference for licensing board exams, but it is also written for the education of a first time bachalaureate degree reader in the biological sciences. Hopefully, it can be read with great interest by the undergraduate student who is undecided in the choice of a career.

In the Preface, I failed to disclose that the term Metabolomics applies to plants, animals, bacteria, and both prokaryotes and eukaryotes. The metabolome for each organism is unique, but from an evolutionary perspective has metabolic pathways in common, and expressed in concert with the environment that these living creatures exist. The metabolome of each has adaptive accommodation with suppression and activation of pathways that are functional and necessary in balance, for its existence. Was it William Faulkner who said in his Nobel Prize acceptance that mankind shall not merely exist, but survive? That seems to be the overlying theme for all of life. If life cannot persist, a surviving “remnant” might continue. The history of life may well be etched into the genetic code, some of which is not expressed.

This work is apportioned into chapters in a sequence that is first directed at the major sources for the energy and the structure of life, in the carbohydrates, lipids, and fats, which are sourced from both plants and animals, and depending on their balance, results in an equilibrium, and a disequilibrium we refer to as disease. There is also a need to consider the nonorganic essentials which are derived from the soil, from water, and from the energy of the sun and the air we breathe, or in the case of water-bound metabolomes, dissolved gases.

In addition to the basic essential nutrients and their metabolic utilization, they are under cellular metabolic regulation that is tied to signaling pathways. In addition, the genetic expression of the organism is under regulatory control by the interaction of RNAs that interact with the chromatin genetic framework, with exosomes, and with protein modulators.This is referred to as epigenetics, but there are also drivers of metabolism that are shaped by the interactions between enzymes and substartes, and are related to the tertiary structure of a protein. The framework for diseases in a separate chapter. Pharmaceutical interventions that are designed to modulate specific metabolic targets are addressed as the pathways are unfolded. Neutraceuticals and plant based nutrition are covered in Chapter 8.

Chapter 1: Metabolic Pathways

Chapter 2. Lipid Metabolism

Chapter 3. Cell Signaling

Chapter 4. Protein Synthesis and Degradation

Chapter 5: Sub-cellular Structure

Chapter 6: Proteomics

Chapter 7: Metabolomics

Chapter 8. Impairments in Pathological States: Endocrine Disorders; Stress Hypermetabolism and Cancer

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Editorials & Publications of Articles (Post) in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Aviva Lev-Ari, PhD, RN

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cardiac and Cardiovascular Surgical Procedures, Frontiers in Cardiology and Cardiovascular Disorders, Genetics & Pharmaceutical, Genome Biology, Genomic Testing: Methodology for Diagnosis, Medical Devices R&D Investment, Personalized and Precision Medicine & Genomic Research on October 16, 2014| Leave a Comment »

Editorials & Publications of Articles (Post)

in e-Books by

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Contributions of Aviva Lev-Ari, PhD, RN

UPDATED on 1/21/2023

Five Bilingual BioMed e-Series – 37 volumes

Curator, Book Editor & Bilingual BioMed e-Series, Editor-in-Chief:

Aviva Lev-Ari, PhD, RN

English Edition: 18 volumes in 17 books, and
Spanish Edition (EDICIÓN EN ESPAÑOL): 19 volumes in 19 books

https://pharmaceuticalintelligence.com/five-bilingual-biomed-e-series/

List of Aviva Lev-Ari’s Articles in English Edition

18 volumes in 17 e-Books

https://lnkd.in/ekWGNqA

Book of Business for LPBI Group’s English Edition, 2013-2021

Series A: Cardiovascular Diseases

(6 books) Kindle Edition

https://www.amazon.com/dp/B07P981RCS?binding=kindle_edition&ref=dbs_dp_rwt_sb_pc_tukn

Series A: Price	Volume 1
Number of Page Downloads
$515	$75
Publication Date	6/21/13
Book URL	http://www.amazon.com/dp/B00DINFFYC
Book Title	Perspectives on Nitric Oxide in Disease Mechanisms
Total # of articles in the volume	42
Aviva’s articles in Volume 1	1.1.2, 1.6.2, 2.2.3, 3.1.1, 3.2.1, 3.2.2, 3.2.3, 3.2.4, 3.3.1, 7.4

Volume 2

$75

11/30/15

http://www.amazon.com/dp/B018Q5MCN8

Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation

Aviva’s articles in Volume 2:

1.1, 1.2, 1.3, 1.4, 1.5, 2.1.1, 2.1.2, 2.1.3, 2.2.1, 2.2.2, 2.2.4, 2.3, 3.1.1.1, 3.1.2.1, 3.1.2.2., 3.1.3.1, 3.2.2, 3.2.3, 3.2.4, 3.2.5, 3.2.6, 3.2.7, 3.2.8, 3.3.1, 3.3.2, 3.3.3, 3.3.4, 4.1.1, 4.2.1, 4.2.2, 4.2.3, 4.2.4, 4.2.5, 4.2.7, 4.2.8, 4.2.9, 4.3.1, 4.3.2, 4.3.3, 4.3.4, 4.3.5, 4.3.6, 4.4.1, 4.4.2, 4.4.3, 4.4.4, 4.5.1, 4.5.2, 4.5.3, 4.5.4, 4.4.5, 5.1.1, 5.1.2, 5.1.3, 5.1.4, 5.1.5, 5.1.6, 5.1.7, 5.1.9, 5.1.10, 5.1.11, 5.1.12, 5.1.13, 5.2.1, 5.2.2, 5.2.3, 5.3.1, 5.4.1, Epilogue to Volume Two

Volume 3

$75

11/29/15

http://www.amazon.com/dp/B018PNHJ84

Etiologies of Cardiovascular Diseases – Epigenetics, Genetics and Genomics

168

Aviva’s articles in Volume 3:

1.2, 1.3.1, 1.3.2, 1.3.3, 1.3.4, 1.3.5, 1.3.6, 1.4.1, 1.5, 2.1.1.1, 2.1.1.2, 2.1.1.3, 2.1.2.4, 2.1.2.5, 2.1.2.6, 2.1.2.7, 2.1.2.8, 2.1.2.9, 2.1.2.11, 2.1.2.12, 2.1.3.1, 2.1.3.2, 2.1.3.3, 2.1.3.4, 2.1.3.6, 2.1.3.7, 2.1.4.2, 2.1.5.1, 2.1.5.2, 2.1.5.5, 2.1.5.6, 2.1.5.7, 2.1.5.8, 2.1.6.1, 2.1.6.3, 2.1.6.4, 2.1.7.1, 2.1.7.2, 2.1.8.3, 2.1.8.5, 2.1.9.1, 2.2.1.3, 2.2.1.5, 2.2.1.6, 2.2.2.1, 2.2.2.2, 2.2.2.7, 2.2.2.8, 2.2.2.9, 2.2.3.1, 2.2.3.2, 2.2.3.3, 2.2.3.6, 2.2.3.7, 2.2.4.1, 2.2.4.2, 2.2.4.3, 2.2.4.4, 2.2.4.5, 2.2.4.6, 2.2.4.7, 2.2.4.9, 2.2.5.1, 2.2.5.3, 2.2.5.7, 2.3.1, 2.3.5, 2.3.6, 2.3.7, 2.4.1, 2.4.3, 2.4.4, 2.4.6, 2.4.9, 2.4.10, 2.4.11, 2.5.4, 2.5.6, 2.6.1, 2.6.2, 3.3.1.1, 3.3.1.2, 3.3.1.3, 3.3.2.1, 3.3.2.2, 3.3.3.1, 3.3.3.2, 3.3.3.3, 3.3.4.1, 3.3.4.2, 3.3.4.3, 3.3.4.4, 3.3.5.1, 3.3.6.1, 3.3.6.3, 3.3.6.4, 3.3.6.5, 3.3.6.6, 3.3.7.1, 3.3.7.2, 3.3.7.3, 3.3.7.4, 3.3.7.5, 3.3.8.1, 3.3.8.2, 3.3.9.1, 3.3.9.2, 3.3.9.3, 3.3.9.4, 3.3.10.1, 4.2, 4.1.1, 4.5.1, 4.5.2, 4.5.3, 4.5.4, 4.5.5, 4.5.6, 4.5.7

Volume 4

$75

12/26/15

http://www.amazon.com/dp/B019UM909A

Therapeutic Promise: Cardiovascular Diseases, Regenerative & Translational Medicine

128

Aviva’s articles in Volume 4:

Part One:
Introduction, 1.2, 1.4, 2.1.1, 2.1.2, 2.1.3, 2.1.4, 2.2.5, 2.2.8, 2.3.1, 2.3.2, 2.3.5, 2.5.5, 2.6.5, 2.6.10, 2.8.2, 2.8.6, 2.8.10, 3.7, 3.10, 3.11, 3.12, 4.1.2, 4.1.3, 4.1.4, 4.1.5, 4.1.6, 4.1.7, 4.2.2, 4.2.3, 4.2.4, 4.2.5, 4.2.6, 4.2.7, 4.2.8, Summary

Part Two:
Introduction, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, 2.1, 2.2, 2.4, 2.5, 3.1, 3.3.2, 3.4, 3.5, 3.6, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 4.10, 4.11, 4.12
Epilogue to Volume Four

Volume 5

$115

12/23/18

https://www.amazon.com/dp/B07MGSFDWR

Pharmacological Agents in Treatment of Cardiovascular Diseases

238

Aviva’s articles in Volume 5:

Single Author Curations

(N=65)

Single Author Scientific Reporting Articles
(N=92)

Co-Curation with one Author
(N=17)

Co-Curation with two Authors

(N=7)

Volume 6

$100

12/24/18

https://www.amazon.com/dp/B07MKHDBHF

Interventional Cardiology for Disease Diagnosis and and Cardiac Surgery for Condition Treatment

154 authored and curated articles
194 Scientific reports
In Total, 348 articleIDs

Aviva’s articles in Volume 6:

Curations:
N = 56
Scientific Reports:
N = 194
ArticleIDs in
Series A, Volume 6:
N = 250

Series B: Frontiers in Genomics Research

(2 book series) Kindle Edition

https://www.amazon.com/gp/product/B0BSDPG2RX?ref_=dbs_p_pwh_rwt_anx_b_lnk&storeType=ebooks

Series B: Price	Volume 1

$200	$75
Publication Date	11/23/15
Book URL	http://www.amazon.com/dp/B018DHBUO6
Book Title	Genomics Orientations for Personalized Medicine
Total # of articles in the volume	188
Aviva’s articles in volume 1	1.6, 2.1, 2.5, 3.4, 3.5, 3.7, 3.8, 4.1, 4.4, 4.5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 6.18, 7.1, 7.2, 7.3, 7.4, 7.5, 8.1, 8.2, 8.3, 8.7, 8.9, 9.1, 9.2, 9.3, 9.4, 9.5, 9.8, 10.1, 10.2, 10.3, 10.8, 11.2, 11.3, 11.5, 11.9, 12.1, 13.5 13.7, 15.1, 15.2, 15.4, 15.6, 15.7, 15.9.1, 15.9.2, 15.9.3, 15.9.5, 15.10, 17.1, 18.3, 18.4, 19.4, 19.5, 20.1, 20.8, 21.1.1, 21.1.2, 21.1.3, 21.1.4, 21.2.1, 21.2.2, 21.2.3, 21.2.4, 21.3.1, 21.3.2, 21.4.2

Volume 2

$125

12/28/19

https://www.amazon.com/dp/B08385KF87

Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology

326

Total articles in Volume: 326.

Aviva’s articles in Volume 2:

Part 1: Aviva = 66;

Part 2: Aviva = 78;

Part 3: Aviva = 25;

Part 4: Aviva = 7;

Part 7: Aviva = 4;

Part 8: Aviva = 6.

Total 121;

Larry + Aviva = 8;

SWJ + Aviva = 3.

Series C: Cancer & Oncology

(2 book series) Kindle Edition

https://www.amazon.com/gp/product/B0BSDWVB3H?ref_=dbs_p_mng_rwt_ser_shvlr&storeType=ebooks

Series C: Price	Volume 1
Number of Page Downloads
$175	$75
Publication Date	8/11/15
Book URL	http://www.amazon.com/dp/B013RVYR2K
Book Title	Cancer Biology and Genomics for Disease Diagnosis
Total # of articles in the volume	162
Aviva’s articles in Volume 1	BOLD are curations: 1.3, 1.4, 1.7, 1.11, 3.5, 3.7, 3.8, 3.9, 3.10, 4.1.2, 4.1.6, 4.2.2, 4.2.5, 4.3.2, 5.1.3, 5.1.6, 5.2.2, 5.2.5, 6.1.2, 6.1.4, 7.1.1, 7.1.5, 7.1.6, 7.2.1, 7.2.3, 7.2.4, 7.2.5, 7.3.5, 7.3.6, 7.4.2, 8.1, 8.3, 9.2, 9.3, 10.3, 10.4, 10.6, 10.7

Volume 2

$100

5/18/17

http://www.amazon.com/dp/B071VQ6YYK

Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery

242

Aviva’s articles in Volume 2:

1.3.2, 8.4, 9.1.2.1, 9.1.2.2, 9.1.2.4, 9.1.2.6, 9.3.1.2, 11.1, 16.6, 19.1, 19.2, 19.3, 19.6, 19.7.1, 19.7.2, 19.8, 20.2.3, 20.2.4, 20.2.5, 20.2.6, 20.3.1, 20.3.2, 20.3.3, 20.3.4, 20.3.5

Series D: BioMedicine – Metabolomics, Immunology, Infectious

Diseases, Reproductive Genomic Endocrinology

(4 book series) Kindle Edition

https://www.amazon.com/gp/product/B08VVWTNR4?ref_=dbs_p_pwh_rwt_anx_b_lnk&storeType=ebooks

Series D: Price	Volume 1
Number of Page Downloads
$325	$75
Publication Date	7/21/15
Book URL	http://www.amazon.com/dp/B012BB0ZF0
Book Title	Metabolic Genomics & Pharmaceutics
Total # of articles in the volume	92
Aviva’s articles in Volume 1	4.3, 4.10, 5.6, 5.7, 5.8, 5.9, 6.10, 7.5, 9.1, 9.4, 9.5, 9.7, 9.8, 9.9

Volume 2 & 3

$115

9/4/17

https://www.amazon.com/dp/B075CXHY1B

The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications

165

Aviva’s articles in each volume,

Volume 2 and Volume 3:

Volume 2

1.11, 1.13, 2.5, 3.3, 3.4,3.5, 4.1, 4.2, 4.3, 5.5, 5.7, 5.10, 6.2, 6.14, 8.6, 8.7, 8.8, 9.3, 9.7, 9.11, Part 3 Summary,

Volume 3

1.2, 1.3, 2.3, 3.2, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 3.10, 3.11, 3.12, 3.13, 3.14, 3.15, 3.16, 3.17, 4.1, 4.2, 5.4, 8.5, 9.5, 9.6, 9.9, 10.1, 10.2, 10.3, 11.1, 11.3, 11.5,

Volume 4

$135

2/2/21

http://www.amazon.com/dp/B08VTFWVKM

Human Reproductive System, Genomic Endocrinology and Cancer Types

Aviva’s articles in Volume 4:

Volume Introduction, 1.1, 1.4, 4.3, 4.6, 6.5, 6.7, 7.2, 7.5, 7.6, 9.2, 9.5, 10.3.1.2, 10.3.2.4, 10.3.2.5, 10.3.3.1, 10.3.3.2, 10.3.3.5, 10.3.4.2, 10.3.4.4, 10.3.4.5

Series E: Patient-Centered Medicine & Precision Medicine

(4 book series) Kindle Edition

https://www.amazon.com/gp/product/B0BSDW2K6C?ref_=dbs_p_mng_rwt_ser_shvlr&storeType=ebooks

Series E: Price	Volume 1
Number of Page Downloads
$274	$49
Publication Date	10/16/2017
Book URL	https://www.amazon.com/dp/B076HGB6MZ
Book Title	The VOICES of Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures
Total # of articles in the volume	87
Aviva’s articles in Volume 1	1.1, 4.1, 5.1.2, 5.5.8, 6.1, 6.2,

Volume 2

$75

12/9/2017

https://www.amazon.com/dp/B078313281

Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders

167

Aviva’s articles in Volume 2

Part One:

1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 2.2.1, 2.3

Part Two:

5.1, 5.4, 5.5, 5.7, 5.8, 5.9, 5.10, 5.11, 6.1.3, 6.2.3, 6.2.4, 6.2.5, 6.3.1, 6.3.3, 6.3.7, 6.3.9, 6.4.3, 6.5.1.1, 6.5.2, 6.5.2.1, 6.5.2.2, 6.5.3.1, 6.5.4, 6.5.5, 6,5,6, 8.9.2, 8.10.2, 9.1, 9.4, 10.1, 10.3, 11.4, 12.6, 13.5, 13.7, 13.8, 13.9, 13.10, 13.11

Volume 3

$75

12/27/2015

http://www.amazon.com/dp/B019VH97LU

Milestones in Physiology & Discoveries in Medicine and Genomics

Aviva’s articles in Volume 3

7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.8, 7.9, 7.10, 7.11

Volume 4

$75

12/30/2017

https://www.amazon.com/dp/B078QVDV2W

Medical 3D BioPrinting – The Revolution in Medicine

136

Aviva’s articles in Volume 4

1.8, 1.14, 2.1, 2.2, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 2.10, 2.11, 3.1, 3.2, 3.4, 3.6, 3.7, 3.8, 3.9, 3.10, 4.10, 4.17, 5.2, 5.3, 6.3, 6.4, 6.5, 6.6, 6.11, 7.1, 7.6, 7.7, 8.2, 9.2, 9.3, 9.4, 9.6, 10.1, 10.2, 10.3, 11.4, 11.5, 12.5, 13.1, 13.4, 13.7

@@@@@@@

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e-Books in Medicine

electronic Table of Contents (eTOCs) of each Volume in the SIXTEEN Volume BioMed e-Series

https://pharmaceuticalintelligence.com/2017/12/12/biomed-e-series-16-volumes-electronic-table-of-contents-of-each-volume/

All 18 volumes in e-Books on the Medicine and Life Sciences shelf in Kindle Store:

English Edition: 18 Volumes in 17 e-Books, Series D; Volume 2&3 in one e-Book
Spanish Edition: 19 Volumes in 19 e-Books

https://www.amazon.com/s/ref=nb_sb_noss?url=search-alias%3Ddigital-text&field-keywords=Aviva+Lev-Ari&rh=n%3A133140011%2Ck%3AAviva+Lev-Ari

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Amazon’s Aviva Lev-Ari Page

Discover books, read about the author, find related products, and more.More about Aviva Lev-Ari

36 results for Kindle Store :

“Aviva Lev-Ari”

English Edition: 18 Volumes in 17 e-Books

Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology (Series B: Frontiers in Genomics Research Book 2)

Book 2 of 2: Series B: Frontiers in Genomics Research | by Stephen J. Williams, Aviva Lev-Ari, et al. | Sold by: Amazon.com Services LLC

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Interventional Cardiology for Disease Diagnosis and Cardiac Surgery for Condition Treatment (Series A: Cardiovascular Diseases Book 6)

Book 6 of 6: Series A: Cardiovascular Diseases | by Justin D. Pearlman, Larry H. Bernstein, et al. | Sold by: Amazon.com Services LLC

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Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics

Book 3 of 6: Series A: Cardiovascular Diseases | by Justin D. Pearlman MD ME PhD MA FACC, Stephen J. Williams PhD, et al. | Sold by: Amazon.com Services LLC

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Human Reproductive System, Genomic Endocrinology and Cancer Types (Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases, Reproductive Genomic Endocrinology Book 4)

Book 3 of 3: Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases, Reproductive Genomic Endocrinology | by Stephen J. Williams, Sudipta Saha, et al. | Sold by: Amazon.com Services LLC

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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)

Book 4 of 4: Series E: Patient-Centered Medicine | by Larry H. Bernstein, Irina Robu, et al. | Sold by: Amazon.com Services LLC

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ARTICLES in e-BOOKS

Series A: e-Books on Cardiovascular Diseases

Content Consultant: Justin D Pearlman, MD, PhD, FACC

Volume One: Perspectives on Nitric Oxide

Sr. Editor: Larry Bernstein, MD, FCAP, Editor: Aviral Vatsa, PhD and Content Consultant: Stephen J Williams, PhD

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B00DINFFYC

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

1.1.2, 1.6.2, 2.2.3, 3.1.1, 3.2.1, 3.2.2, 3.2.3, 3.2.4, 3.3.1, 7.4

Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation

Curators: Justin D Pearlman, MD, PhD, FACC, Larry H Bernstein, MD, FCAP, Aviva Lev-Ari, PhD, RN

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B018Q5MCN8

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

Volume Three: Etiologies of CVD: Epigenetics, Genetics & Genomics

Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B018PNHJ84

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

1.2, 1.3.1, 1.3.2, 1.3.3, 1.3.4, 1.3.5, 1.3.6, 1.4.1, 1.5, 2.1.1.1, 2.1.1.2, 2.1.1.3, 2.1.2.4, 2.1.2.5, 2.1.2.6, 2.1.2.7, 2.1.2.8, 2.1.2.9, 2.1.2.11, 2.1.2.12, 2.1.3.1, 2.1.3.2, 2.1.3.3, 2.1.3.4, 2.1.3.6, 2.1.3.7, 2.1.4.2, 2.1.5.1, 2.1.5.2, 2.1.5.5, 2.1.5.6, 2.1.5.7, 2.1.5.8, 2.1.6.1, 2.1.6.3, 2.1.6.4, 2.1.7.1, 2.1.7.2, 2.1.8.3, 2.1.8.5, 2.1.9.1, 2.2.1.3, 2.2.1.5, 2.2.1.6, 2.2.2.1, 2.2.2.2, 2.2.2.7, 2.2.2.8, 2.2.2.9, 2.2.3.1, 2.2.3.2, 2.2.3.3, 2.2.3.6, 2.2.3.7, 2.2.4.1, 2.2.4.2, 2.2.4.3, 2.2.4.4, 2.2.4.5, 2.2.4.6, 2.2.4.7, 2.2.4.9, 2.2.5.1, 2.2.5.3, 2.2.5.7, 2.3.1, 2.3.5, 2.3.6, 2.3.7, 2.4.1, 2.4.3, 2.4.4, 2.4.6, 2.4.9, 2.4.10, 2.4.11, 2.5.4, 2.5.6, 2.6.1, 2.6.2, 3.3.1.1, 3.3.1.2, 3.3.1.3, 3.3.2.1, 3.3.2.2, 3.3.3.1, 3.3.3.2, 3.3.3.3, 3.3.4.1, 3.3.4.2, 3.3.4.3, 3.3.4.4, 3.3.5.1, 3.3.6.1, 3.3.6.3, 3.3.6.4, 3.3.6.5, 3.3.6.6, 3.3.7.1, 3.3.7.2, 3.3.7.3, 3.3.7.4, 3.3.7.5, 3.3.8.1, 3.3.8.2, 3.3.9.1, 3.3.9.2, 3.3.9.3, 3.3.9.4, 3.3.10.1, 4.1.1, 4.5.1, 4.5.2, 4.5.3, 4.5.4, 4.5.5, 4.5.6, 4.5.7

Volume Four: Therapeutic Promise: CVD, Regenerative & Translational Medicine

Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B019UM909A

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

Part One:

Introduction, 1.2, 1.4, 2.1.1, 2.1.2, 2.1.3, 2.1.4, 2.2.5, 2.2.8, 2.3.1, 2.3.2, 2.3.5, 2.5.5, 2.6.5, 2.6.10, 2.8.2, 2.8.6, 2.8.10, 3.7, 3.10, 3.11, 3.12, 4.1.2, 4.1.3, 4.1.4, 4.1.5, 4.1.6, 4.1.7, 4.2.2, 4.2.3, 4.2.4, 4.2.5, 4.2.6, 4.2.7, 4.2.8, Summary

Part Two:

Introduction, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, 2.1, 2.2, 2.4, 2.5, 3.1, 3.3.2, 3.4, 3.5, 3.6, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 4.10, 4.11, 4.12, Epilogue to Volume Four

Volume Five: Pharmaco-Therapies for CVD

Curators: Justin D Pearlman, MD, PhD, FACC, Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/biomed-e-books/series-a-e-books-on-cardiovascular-diseases/volume-five-pharmaco-therapies-for-cvd/

Aviva Lev-Ari, PhD, RN, Volume Co-Editor and Curator – Articles in Volume Five:

Productive Collaborations among Team members: N = 24

Curators: Justin D. Pearlman, MD, PhD, FACC, Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

1.1, 1.9, 10.2, 10.5

Curators: Larry H. Bernstein, MD FCAP, Justin D. Pearlman, MD, PhD, FACC, and Aviva Lev-Ari, PhD, RN

10.3, 17.1.3, 17.2.1

Authors and Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

4.17, 5.6.7, 5.8.3, 10.4, 17.2.2, 17.3.10, 17.4.1, 17.4.6, 18.2.1, 18.2.2, 19.1.6, 20.2.7

Curators: Lal, V., Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

4.10,

Curators: Aviva Lev-Ari, PhD, RN and Larry H. Bernstein, MD, FCAP

5.1, 5.7

Curators: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

7.9, 17.4.3

Aviva Lev-Ari, PhD, RN, Volume Co-Editor and Curator – Single Author Curations, Single Author of Scientific Reporting articles and Co-curations in CVD, Volume 5 by ArticleID.

Single Author Curations

(N=66)

Single Author Reporting Articles

(N=92)

Co-Curation with one Author

(N=17)

Co-Curation with two Authors

(N=7)

Classification of Drugs, 1.3, 2.1, 2.2, 2.3, 2.4, 2.6, 2.7, 2.8, 2.12, 2.13, 2.14, 4.1, 4.2, 4.3, 4.6, 4.13, 5.3, 5.4, 5.6.6, 5.9, 6.6, 6.7, 6.8, 6.10, 7.1, 7.10, 8.1, 8.2, 9.1, 9.4, 9.7, 9.8, 9.9, 10.1, 11.1, 11.2, 11.4, 11.5, 11.6, 11.7, 11.8, 12.1, 12.2, 12.3, 12.4, 12.5, 12.6, 12.7, 12.8, 12.9, 12.10, 12.11, 12.12, 12.13, 16.1, 17.2.3, 17.6.1, 18.1.3, 18.2.6, 19.1.5, 19.2.1, 19.2.4, 19.2.5, 19.3.1, 20.2.4

1.2, 1.4, 1.5, 1.6, 1.7, 2.5, 2.9, 2.10, 2.11, 2.15, 2.16, 3.1, 3.2, 3.3, 3.4, 4.4, 4.5, 4.7, 4.8, 4.9, 4.11, 4.14, 4.15, 4.16, 5.2, 5.5, 5.6.1, 5.6.2, 5.6.3, 5.6.4, 5.6.5, 5.6.8, 5.6.9, 5.8.1, 5.8.2, 5.11, 5.12, 5.13, 6.1, 6.2, 6.3, 6.4, 6.5, 6.9, 6.11, 6.12, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.11, 8.3, 8.4, 8.5, 9.2, 9.3, 9.5, 9.6, 9.10, 9.12, 9.13, 10.6, 11.3, 13.4, 13.5, 16.4, 16.5, 16.6, 16.7, 17.1.2, 17.1.4, 17.1.5, 17.3.2, 17.3.3, 17.3.5, 17.3.12, 17.4.5, 17.5.1, 17.5.2, 17.5.3, 17.6.2, 18.1.2, 18.2.7, 19.2.2, 19.2.3, 19.3.2, 20.2.5, 20.2.6, 20.3.2

4.17, 5.1, 5.6.7, 5.7, 5.8.3, 7.9, 10.4, 17.2.1, 17.2.2, 17.3.10, 17.4.1, 17.4.3, 17.4.6, 18.2.1, 18.2.2, 19.1.6, 20.2.7,

1.1, 1.9, 4.10, 10.2, 10.3, 10.5, 17.1.3

Volume Six: Interventional Cardiology, Cardiac Surgery and Cardiovascular Imaging for Disease Diagnosis and Guidance of Treatment

Co-Editors: Justin D Pearlman, MD, PhD, FACC, Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/biomed-e-books/series-a-e-books-on-cardiovascular-diseases/volume-six-interventional-cardiology-and-cardiac-surgery/

Aviva Lev-Ari, PhD, RN, Volume Co-Editor and Curator – Single Author Curations, Single Author of Scientific Reporting articles and Co-curations in CVD, Volume 6 by ArticleID.

Curators:

Larry H. Bernstein, MD, FCAP

and

Aviva Lev-Ari, PhD, RN

N = 35

1.2.3, 1.3.6, 3.3.5.1, 3.3.5.2, 3.3.5.3, 4.4.2, 6.2.8, 6.2.9, 7.2.3, 7.2.6, 9.4.1, 9.6.4, 9.6.6, 10.1.1, 10.1.6, 10.1,7, 10.1.8, 10.1.9, 10.1.11, 10.1.14, 10.2.1.3, 11.1.2, 11.1.3, 11.2.6, 12.3.1.2, 12.3.4.2, 12.3.4.3, 12.3.4.5, 12.4.1.1, 12.4.2.1, 13.2.12, 13.2.13, 13.4.1, 14.3.2, 14.3.5

Author: Justin Pearlman,

MD, PhD, FACC,

Author: Larry H Bernstein, MD, FCAP

and Curator:

Aviva Lev-Ari, PhD, RN

N = 1

2.6

Curators:

Justin D. Pearlman, MD, PhD, FACC

and

Aviva Lev-Ari, PhD, RN

N = 13

2.7, 4.1.4, 4.1.5, 8.4.2, 8.4.4, 8.4.5, 8.5.1, 8.5.2, 8.7.4, 8.8.1, 10.1.10, 11.1.7, 13.3.2

Curators:

Aviva Lev-Ari, PhD, RN

and

Larry H. Bernstein, MD, FCAP

N = 1

9.4.5

Authors:

Larry H Bernstein, MD, FCAP,

Justin Pearlman, MD, PhD, FACC

and

Curator: Aviva Lev-Ari, PhD, RN

N = 2

3.3.5.5, 10.1.4

Aviva Lev-Ari, PhD, RN

Curations:

N = 56

Scientific Reports:

N = 194

N = 250

Curations

N = 56

1.3.2, 2.1, 3.1.1, 3.1.2, 3.1.3, 3.1.4, 3.2.4, 3.2.6, 3.3.2.8, 3.3.2.12, 3.3.2.13, 3.3.3.2, 3.3.4.2, 3.3.5.6, 4.1.6, 4.3.2, 5.1.3, 5.1.4, 5.1.5, 6.2.7, 7.1.1, 7.2.4, 8.1.3, 8.1.6, 8.1.17, 8.4.1, 8.6.5, 8.9.2, 9.4.9, 9.5.1, 10.1.3, 10.1.5, 10.2.2.1, 10.2.2.3, 10.2.2.5, 10.3.1.5, 11.1.1, 11.1.5, 11.1.6, 11.2.2, 11.2.3, 11.2.4, 11.2.7, 11.3.1, 11.3.7, 11.3.10, 11.3.11, 12.1, 12.3.1.1. 12.3.2.2, 12.3.2.3, 12.3.4.7, 12.4.1.3, 13.1.8, 13.3.5, 14.6.1

Aviva Lev-Ari, PhD, RN

Curations:

N = 56

Scientific Reports:

N = 194

N = 250

Scientific Reporting

N = 194

1.1.4, 1.2.1, 1.2.2, 1.3.1, 1.3.4, 1.3.5, 1.3.7, 1.3.8, 1.3.10, 2.2, 2.3, 2.5, 2.9, 2.10, 2.11, 3.1.5, 3.2.2, 3.2.3, 3.2.5, 3.3.1.1, 3.3.1.2, 3.3.1.3, 3.3.2.1, 3.3.2.2, 3.3.2.3, 3.3.2.4, 3.3.2.5, 3.3.2.6, 3.3.2.7, 3.3.2.9, 3.3.2.10, 3.3.2.11, 3.3.2.14, 3.3.3.1, 4.1.1, 4.1.7, 4.2.1, 4.2.2, 4.3.1, 4.4.1, 4.4.3, 5.1.6, 5.1.7, 5.1.8, 5.1.10, 5.1.11, 5.1.12, 5.1.13, 5.2.3, 5.2.4, 6.2.3, 6.2.6, 6.2.10, 6.3.1, 6.3.2, 6.3.3, 7.1.2, 7.1.3, 7.2.1, 7.2.5, 7.3.1, 8.1.4, 8.1.5, 8.1.7, 8.1.8, 8.1.9, 8.1.10, 8.1.11, 8.1.12, 8.1.13, 8.1.14, 8.1.15, 8.1.16, 8.2.1, 8.2.2, 8.2.3, 8.2.4, 8.2.5, 8.3.1, 8.3.2, 8.3.3, 8.3.4, 8.3.5, 8.3.6, 8.4.3, 8.4.6, 8.4.7, 8.6.1, 8.6.2, 8.6.3, 8.6.4, 8.7.1, 8.7.2, 8.7.3, 8.7.5, 8.9.1, 8.10.1, 8.11.1, 9.2, 9.3, 9.4.2, 9.4.3, 9.4.4, 9.4.6, 9.4.7, 9.4.8, 9.6.3, 10.1.2, 10.1.12, 10.1.13, 10.2.1.1, 10.2.1.2, 10.2.1.4, 10.2.2.2, 10.2.2.4, 10.2.2.6, 10.2.2.7, 10.3.1.2, 10.3.1.3, 10.3.1.4, 10.3.2.2, 10.3.2.3, 11.1.4, 11.1.8, 11.1.9, 11.1.10, 11.2.1, 11.2.8, 11.2.9, 11.2.10, 11.3.2, 11.3.3, 11.3.4, 11.3.5, 11.3.6, 11.3.8, 11.3.9, 12.2, 12.3.1.3, 12.3.1.4, 12.3.2.1, 12.3.3.1, 12.3.3.2, 12.3.4.1, 12.3.4.4, 12.3.4.6, 12.4.1.2, 12.4.2.2,12.4.2.3, 12.4.2.4, 12.4.2.6, 12.4.2.7, 12.4.2.8, 13.1.1, 13.1.2, 13.1.3, 13.1.4, 13.1.5, 13.1.6, 13.1.7, 13.1.9, 13.2.1, 13.2.2, 13.2.3, 13.2.4, 13.2.5, 13.2.6, 13.2.7, 13.2.8, 13.2.9, 13.2.10, 13.2.11, 13.2.14, 13.2.15, 13.2.16, 13.2.17, 13.2.18, 13.3.1, 13.3.3, 13.3.4, 13.3.6, 13.3.7, 13.5.1, 13.5.2, 13.6.1, 14.2.1, 14.2.2, 14.2.3, 14.2.4, 14.2.6, 14.3.3, 14.3.4, 14.5.1, 14.5.2

Series B: e-Books on Genomics & Medicine

Content Consultant: Larry H Bernstein, MD, FCAP

Volume 1: Genomics and Individualized Medicine

Sr. Editor: Stephen J Williams, PhD

Editors: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B018DHBUO6

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

1.6, 2.1, 2.5, 3.4, 3.5, 3.7, 3.8, 4.1, 4.4, 4.5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 6.18, 7.1, 7.2, 7.3, 7.4, 7.5, 8.1, 8.2, 8.3, 8.7, 8.9, 9.1, 9.2, 9.3, 9.4, 9.5, 9.8, 10.1, 10.2, 10.3, 10.8, 11.2, 11.3, 11.4, 11.5, 11.9, 12.1, 13.5 13.7, 15.1, 15.2, 15.4, 15.6, 15.7, 15.9.1, 15.9.2, 15.9.3, 15.9.5, 15.10, 17.1, 18.3, 18.4, 19.4, 19.5, 20.1, 20.8, 21.1.1, 21.1.2, 21.1.3, 21.1.4, 21.2.1, 21.2.2, 21.2.3, 21.2.4, 21.3.1, 21.3.2, 21.4.2

Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

Stephen J. Williams, PhD, Senior Editor Prof. Marcus W. Feldman Content Consultant and Aviva Lev-Ari, PhD, RN, Editor

Total articles in Volume: 326. Part 1: Aviva 66;

Part 2: Aviva 78;

Part 3: Aviva 25;

Part 4: Aviva 7;

Part 7: Aviva 4;

Part 8: Aviva 6.

Total 121;

Larry + Aviva 8;

SWJ + Aviva 3.

Series C: e-Books on Cancer & Oncology

Content Consultant: Larry H Bernstein, MD, FCAP

Volume One: Cancer and Genomics

Sr. Editor: Stephen J Williams, PhD

Editors: Ritu Saxena, PhD, Tilda Barliya, PhD

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B013RVYR2K

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

1.3, 1.4, 1.7, 1.11, 3.5, 3.7, 3.8, 3.9, 3.10, 4.1.2, 4.1.6, 4.2.2, 4.2.5, 4.3.2, 5.1.3, 5.1.6, 5.2.2, 5.2.5, 6.1.2, 6.1.4, 7.1.1, 7.1.5, 7.1.6, 7.2.1, 7.2.3, 7.2.4, 7.2.5, 7.3.5, 7.3.6, 7.4.2, 8.1, 8.3, 9.2, 9.3, 10.3, 10.4, 10.6, 10.7

Volume Two: Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery

Authors, Curators and Editors: Larry H Bernstein, MD, FCAP and Stephen J Williams, PhD

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B071VQ6YYK

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

1.3.2, 8.4, 9.1.2.1, 9.1.2.2, 9.1.2.4, 9.1.2.6, 9.3.1.2, 11.1, 16.6, 19.1, 19.2, 19.3, 19.6, 19.7.1, 19.7.2, 19.8, 20.2.3, 20.2.4, 20.2.5, 20.2.6, 20.3.1, 20.3.2, 20.3.3, 20.3.4, 20.3.5

Series D: e-Books on BioMedicine

Volume 1: Metabolic Genomics & Pharmaceutics

Author, Curator and Editors: Larry H Bernstein, MD, FCAP

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B012BB0ZF0

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

4.3, 4.10, 5.6, 5.7, 5.8, 5.9, 6.10, 7.5, 9.1, 9.4, 9.5, 9.7, 9.8, 9.9

Volume 2 & 3: The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications

Available on Kindle Store @ Amazon.com

https://www.amazon.com/dp/B075CXHY1B

Articles in e-Book by Aviva Lev-Ari, PhD, RN

Volume 2

1.11, 1.13, 2.5, 3.3, 3.4,3.5, 4.1, 4.2, 4.3, 5.5, 5.7, 5.10, 6.2, 8.6, 8.7, 8.8, 9.3, 9.7, 9.11, Part 3 Summary,

Volume 3

1.2, 1.3, 2.3, 3.2, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 3.10, 3.11, 3.12, 3.13, 3.14, 3.15, 3.16, 3.17, 4.1, 4.2, 5.4, 8.5, 9.5, 9.6, 9.9, 10.1, 10.2, 10.3, 11.1, 11.3, 11.5,

Volume 4

Volume Introduction, 1.1, 1.4, 4.3, 4.6, 6.5, 6.7, 7.2, 7.5, 7.6, 9.2, 9.5, 10.3.1.2, 10.3.2.4, 10.3.2.5, 10.3.3.1, 10.3.3.2, 10.3.3.5, 10.3.4.2, 10.3.4.4, 10.3.4.5

Series E:

Patient-centric Medicine

Content Consultant: Larry H Bernstein, MD, FCAP

Volume 1: The VOICES of Patients, Hospital CEOs, Health Care Providers, Care Givers and Families: Personal Experience with Critical Care and Invasive Medical Procedures

Author, Curator and Editor: Larry H Bernstein, MD, FCAP and Gail Thornton, MSc, PhD(c)

On Amazon.com since 10/16/2017

https://www.amazon.com/dp/B076HGB6MZ

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

1.1, 4.1, 5.1.2, 5.5.8, 6.1, 6.2

Volume 2: Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders – Conversion Format stage

Author, Curator and Editor: Larry H Bernstein, MD, FCAP

Available on Kindle Store @ Amazon.com since 12/9/2017

https://www.amazon.com/dp/B078313281

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

Part One:

1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 2.2.1, 2.3

Part Two:

5.1, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 5.10, 5.11, 6.1.3, 6.2.3, 6.2.4, 6.2.5, 6.3.1, 6.3.3, 6.3.7, 6.3.9, 6.4.3, 6.5.1.1, 6.5.2.1, 6.5.2.2, 6.5.3.1, 6.5.4, 6.5.5, 8.11, 9.1, 9.4, 10.1, 10.3, 12.6, 13.5, 13.7, 13.8, 13.9, 13.10, 13.11

Volume 3: Milestones in Physiology & Discoveries in Medicine and Genomics, on Amazon.com since 12/27/2015

Author, Curator and Editor: Larry H Bernstein, MD, FCAP

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B019VH97LU

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.8, 7.9, 7.10, 7.11

Volume 4: Medical 3D BioPrinting – The Revolution in Medicine

Editors: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Available on Kindle Store @ Amazon.com since 12/30/2017

https://www.amazon.com/dp/B078QVDV2W

Articles in e-Book by Aviva Lev-Ari, PhD, RN:

Aviva Lev-Ari, PhD, RN, Editor and Curator,1.8, 1.14, 2.1, 2.2, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 2.10, 2.11, 3.1, 3.2, 3.4, 3.6, 3.7, 3.8, 3.9, 4.10, 4.12, 4.16, 5.2, 5.3, 6.3, 6.4, 6.5, 6.6, 7.1, 7.6, 7.7, 8.2, 9.2, 9.3, 9.4, 9.6, 10.1, 10.2, 10.3, 11.4, 11.5, 12.5, 13.1, 13.4

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Mapping the Universe of Pharmaceutical Business Intelligence: The Model developed by LPBI and the Model of Best Practices LLC

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, BioSimilars, CANCER BIOLOGY & Innovations in Cancer Therapy, Conference Coverage with Social Media, Drug Delivery Platform Technology, Ecosystems & Industrial Concentration in the Medical Device Sector, Exec Compensation in the Cardiac & Vascular Repair Tools Subsegment, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Genetics & Pharmaceutical, Genome Biology, Genomic Testing: Methodology for Diagnosis, Health Law & Patient Safety, HealthCare IT, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, International Global Work in Pharmaceutical, Investment in Technological Breakthrough, Leadership, Power, Social Interlocking Connections, Massachusetts Niche Suppliers and National Leaders, Medical and Population Genetics, Medical Devices R&D Investment, Medical Imaging Technology, Molecular Genetics & Pharmaceutical, Patents, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacogenomics, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Stem Cells for Regenerative Medicine, Technology Transfer: Biotech and Pharmaceutical, Translational Science on October 13, 2014| Leave a Comment »

Mapping the Universe of Pharmaceutical Business Intelligence: The Model developed by LPBI and the Model of Best Practices LLC

Author and Curator of Model A: Aviva Lev-Ari, PhD, RN

Reporter on Model B: Aviva Lev-Ari, PhD, RN

This article provides the e-Reader with a MAP for navigation through two different Business Models that Co-exist in the EcoSystem of an industry called Pharmaceutical Business Intelligence.

Model A: is represented by Six Ventures of Leaders in Pharmaceutical Business Intelligence (LPBI), based in Boston, Philadelphia, CT, CA and Israel

Model B: is represented by Best Practices, LLC, headquartered in Chapel Hill, NC, with Offices in NYC and in Mumbai, India.

We concluded that the two models are viable, represent fast growth, the models and non-competing and are in full complementarity, thus, expanding the domain and the practice of the industrial sector, aka, Pharmaceutical Business Intelligence.

Model A:

Leaders in Pharmaceutical Business Intelligence (LPBI),

Boston, Philadelphia, CT, CA and Israel

VISION

Funding, Deals & Partnerships

Team members

Our Growth Needs: Leaders in Pharmaceutical Business Intelligence

Our Business Portfolio

VENTURE #1:

e-Publishing: Medicine, HealthCare, Life Sciences, BioMed, Pharmaceutical

Open Access Online Scientific Journal

http://pharmaceuticalintelligence.com Site statistics http://pharmaceuticalintelligence.com/wp-admin/index.php?page=stats

Scoop.it!.com

VENTURE #2:

1. BioMedical e-Books e-Series: Cardiovascular, Genomics, Cancer, BioMed, Patient Centered Medicine

http://pharmaceuticalintelligence.com/biomed-e-books/

2. on Amazon’s Kindle e-Books List since 6/2013

Perspectives on Nitric Oxide in Disease Mechanisms

3. Plans for Volume 1,2,3 – Hardcover

Cardiovascular Diseases: Causes, Risks and Management – Volume 1,2,3 – Hardcover

VENTURE #3:

International Scientific Delegations

http://pharmaceuticalintelligence.com/scientific-delegation/

Shanghai, May 2015
Barcelona, Spain, November 2015
Amsterdam, May 2016
Geneva, November 2016

VENTURE #4:

Funding, Deals & Partnerships

http://pharmaceuticalintelligence.com/joint-ventures/

VENTURE #5:

IP Invented HERE!

1. Development of a NEW Nitric Oxide monitor to Alpha Szenszor Inc. sensor portfolio. A concept for a low cost POC e-nose, capable of real time ppb detection of Cancer The Cancer Team at Leaders in Pharmaceutical Business Intelligence under the leadership of Dr. Williams

2. Development of a NEW Nitric Oxide monitor to Alpha Szenszor Inc. sensor portfolio. A concept for Inhaled Nitric Oxide for the Adult HomeCare Market – IP by Dr. Pearlman and Dr. A. Lev-Ari

a. iknow iNO is i-kNOw – Inhaled Nitric Oxide for the HomeCare Markethttp://pharmaceuticalintelligence.com/2013/10/16/iknow-ino-is-i-know-inhaled-nitric-oxide-for-the-homecare-market/

b. electronic Book on Nitric Oxide by Nitric Oxide Team @ Leaders in Pharmaceutical Business Intelligence (LPBI)

Perspectives on Nitric Oxide in Disease Mechanisms

http://www.amazon.com/dp/B00DINFFY

c. The rationale and use of inhaled NO in Pulmonary Artery Hypertension and Right Sided Heart Failure Larry H. Bernstein 8/20/2012

d. Inhaled Nitric Oxide in Adults: Clinical Trials and Meta Analysis Studies – Recent Findings

Aviva Lev-Ari, PhD, RN, 6/2/2013

e. Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care

Aviva Lev-Ari, PhD, RN, 6/3/2013

3. Cancer Genomics for NEW product development in diagnosis and treatment of Cancer Patients using sensory technology with applications for Radiation Therapy –The Cancer Team at Leaders in Pharmaceutical Business Intelligence under leadership of TBA

4. Developing Mitral Valve Disease: MRI Methods and Devices for Percutaneous Mitral Valve Replacement and Mitral Valve Repair Augmentation of Patented Technology using RF – Dr. Pearlman’s IP Non-Hardware Mitral Annuloplasty – Dr. Justin D. Pearlman

http://pharmaceuticalintelligence.com/joint-ventures/valvecure-llc/non-hardware-mitral-annuloplasty-dr-justin-d-pearlman/

5. Novel Technology using MRI for Vascular Lesions, Tumors, Hyperactive Glands and non-Surgical Cosmetic Reconstruction – Dr. Pearlman’s IP

http://pharmaceutica lintelligence.com/biomed-e-books/series-a-e-books-on-cardiovascular-diseases/httppharmaceuticalintelligence-combiomed-e-bookscardiovascular-diseases-causes-risks-and-management/cvd-business-affairs/mitral-valve-disease-mri-methods-and-devices/

VENTURE # 6:

PRESS Coverage of Conferences

http://pharmaceuticalintelligence.com/press-coverage/

Model B:

Best Practices, LLC, Chapel Hill, NC, Mumbai, India, Branch in New York

Best Practices, LLC
6350 Quadrangle Drive, Suite 200,
Chapel Hill, NC 27517

+1 919-403-0251

SOURCE

http://www.best-in-class.com/sitemap

Best Practices, LLC is a leading benchmarking research and consulting firm. We provide access to critical business benchmark metrics and best practices.
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Personalized Medicine Coalition (PMC) – Upcoming Events

Posted in Academic Publishing, Personalized and Precision Medicine & Genomic Research on October 9, 2014| Leave a Comment »

Personalized Medicine Coalition (PMC) – Upcoming Events

Reporter: Aviva Lev-Ari, PhD, RN

About PMC

PMC promotes the advancement of personalized medicine, by addressing regulatory, reimbursement, privacy, ethical, and educational issues critical to the field. Based on the diversity of its membership, PMC has become the preeminent voice shaping policy about and increasing investment in personalized medicine.

The Coalition:

• Provides opinion leadership on public policy issues that affect personalized medicine;

• Helps educate policymakers in government, industry, and academia about the benefits of personalized medicine; and

• Serves as a forum for identifying and informing others of public policies that could advance or impede the development of personalized medicine

EXECUTIVE COMMITTEE

Edward Abrahams, Ph.D.

President

Personalized Medicine Coalition

William S. Dalton, M.D., Ph.D.

(Chair – PMC)

M2Gen/Moffitt Cancer Center

Stephen L. Eck, M.D., Ph.D.

(Vice Chair – PMC)

Astellas Pharma Global

Development

D. Stafford O’Kelly

(Treasurer – PMC)

Abbott Molecular (Ret.)

Amy P. Abernethy, M.D., Ph.D.

(Secretary – PMC)

Duke University Medical Center

J. Brian Munroe

(Past President & Chair – PMC)

Endo Pharmaceuticals

Boar d of Directors

Steven D. Averbuch, M.D.

Bristol-Myers Squibb Company

Patrick J. Balthrop

Luminex Corporation

Paul R. Billings, M.D., Ph.D.

Life Technologies

Jeffrey Cossman, M.D.

United States Diagnostic

Standards (USDS)

Neil de Crescenzo

Emdeon

Donna R Cryer, J.D.

Global Liver Foundation

Felix W. Frueh, Ph.D.

Opus Three, LLC

Tim Garnett, FRCOG, MFFP, FFPM

Eli Lilly and Company

Julie K. Goonewardene

Member, Board of Trustees,

American Medical Association

1710 Rhode Island Ave., NW, Suite 700

Washington, DC 20036

P: 202.589.1770

pmc@personalizedmedicinecoalition.org

Michael Kolodziej, M.D.

Aetna

Lawrence J. Lesko, Ph.D., F.C.P.

University of Florida

Aidan Power, M.B.B.Ch., M.Sc.,

M.R.C Psych.

Pfizer Worldwide

Lori M. Reilly, Esq.

PhRMA

Wayne A. Rosenkrans, Jr., Ph.D.

(Past Chair PMC)

MIT (Ret.)

Jared N. Schwartz, M.D., Ph.D.

Leica Biosystems

Michael J. Vasconcelles, M.D.

Takeda Pharmaceuticals

International Company

SOURCE

http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/pmc_membership_brochure.pdf

Upcoming Events

.
October 21, 2014

Better Science, Better Health: New Trial Pathways and Better Patient Data

Event website »
.
October 27, 2014

2014 | Medical Innovation Summit

Now, it’s Personal
Cancer Treatment and Personalized Medicine

Event website »
.
October 29, 2014

The 6th Annual Personalized & Precision Medicine Conference

Event website »
.
November 06, 2014

2014 Cancer Center Business Summit

Read More »
.
November 11, 2014

10th Annual Boston Reception

Read More »
.
November 12, 2014

10th Annual Personalized Medicine Conference

Event website »
.
November 17, 2014

The Third Annual Evidence-Based Reimbursement Summit

Read More »
.
December 05, 2014

12th Annual Dr. Roizen’s Personalized, Preventive, and Integrative Medicine Conference

The Future of Healthcare with a Focus on Women’s Health

Event website »
.
January 26, 2015

Personalized Medicine World Conference 2015: Silicon Valley

Read More »
.
March 17, 2015

26th Annual Cancer Progress Conference

Event website »

SOURCE

See more at: http://www.personalizedmedicinecoalition.org/Events#sthash.gSaNVC7A.dpuf

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10th Annual Personalized Medicine Conference at the Harvard Medical School, November 12-13, 2014, The Joseph B. Martin Conference Center at Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA

Posted in Academic Publishing, Conference Coverage with Social Media, Genome Biology, Genomic Testing: Methodology for Diagnosis, Genomics Pharmacy, Personalized and Precision Medicine & Genomic Research on October 9, 2014| Leave a Comment »

10th Annual Personalized Medicine Conference at the Harvard Medical School, November 12-13, 2014, The Joseph B. Martin Conference Center at Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA

2014 Personalized Medicine Program

Partners HealthCare Personalized Medicine

Harvard Business School

Harvard Medical School

American Association for Cancer Research

Personalized Medicine Coalition

10th Annual Personalized Medicine Conference at the

Harvard Medical School

November 12-13, 2014

The Joseph B. Martin Conference Center

Harvard Medical School

77 Avenue Louis Pasteur, Boston, MA

Announcement

LEADERS IN PHARMACEUTICAL BUSINESS INTELLIGENCE

will cover the event for the Scientific Media

Dr. Lev-Ari will be in attendance at the Pre-event Reception on 11/11/2014 @Hotel Commonwealth, Boston and on 11/12 and 11/13/2014 – Covering the Event in REALTIME using Social Media

AGENDA

http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx

10th Annual Personalized Medicine Conference at the Harvard Medical School, November 12-13, 2014, The Joseph B. Martin Conference Center at Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA

Reporter: Aviva Lev-Ari, PhD, RN

2014 Personalized Medicine Program

Partners HealthCare, HMS, HBS

November 12-13, 2014,

The Joseph B. Martin Conference Center at Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA

Event Home Page

http://personalizedmedicine.partners.org/education/personalized-medicine-conference/default.aspx

About the The 10th Annual Personalized Medicine Conference

The Personalized Medicine Conference is an annual two-day event co-hosted and presented by Partners HealthCare Personalized Medicine, Harvard Business School, and Harvard Medical School in association with the American Association for Cancer Research and Personalized Medicine Coalition. Widely considered the most prestigious event in the field, this conference attracts hundreds of national and international thought leaders across multiple disciplines as speakers, panelists, and attendees.

See more at: http://personalizedmedicine.partners.org/education/personalized-medicine-conference/default.aspx#sthash.TbFlbDn6.dpuf

AGENDA

http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx

Personalized Medicine Conference Speakers

Speakers for the 2014 Personalized Medicine Conference are being added as they are confirmed. Please refer to the Program for the topics being discussed.

SOURCE

http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Speakers.aspx

SPEAKERS

Personalized Medicine Conference

Speakers for the 2014 Personalized Medicine Conference are being added as they are confirmed. Please refer to the Program for the topics being discussed.

– See more at: http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Speakers.aspx#sthash.MnMgQjdA.dpuf

LEADERS IN PHARMACEUTICAL BUSINESS INTELLIGENCE

Editorials of event coverage via our Open Access Scientific Journal

http://pharmaceuticalintelligence.com

Scientific Journal Site Statistics

Date |Views to Date |# of articles |NIH Clicks |Nature Clicks

07/29/2013 217,356 1,138 1,389 705
12/01/2013 287,645 1,428 1,676 828
02/09/2014 325,039 1,665 1,793 892
03/05/2014 338,958 1,717 1,830 965
03/21/2014 347,667 1,750 1,838 974

03/31/2014 352,683 1,768 1,869 991

05/12/2014 373.696 1,878 1,944 1,035

06/18/2014 393,111 1,992 1,982 1,087

7/27/2014 418,570 2,098 2.050 1,124

9/2/2014 444,222 2,226 2,104 1,170

10/9/2014 471,117 2,337 2,147 1,216

11/4/2014 492,736 2,471 2,194 1,234

Pre e-Pub e-Books Flyers

Series A: e-Books on Cardiovascular Diseases

Series A Content Consultant: Justin D Pearlman, MD, PhD, FACC

VOLUME THREE

Etiologies of Cardiovascular Diseases:

Epigenetics, Genetics and Genomics

Larry H Bernstein, MD, FCAP, Senior Editor, Author and Curator

and

on TWITTER follow us @

@pharma_BI

@AVIVA1950

Series C: e-Books on Cancer & Oncology

Volume One: Cancer Biology and Genomics for Disease Diagnosis

http://pharmaceuticalintelligence.com/biomed-e-books/series-c-e-books-on-cancer-oncology/cancer-biology-and-genomics-for-disease-diagnosis/

Volume Two: Therapies in Cancer – Surgery, Radiation, Chemo and Immunotherapies

http://pharmaceuticalintelligence.com/biomed-e-books/series-c-e-books-on-cancer-oncology/volume-2-immunotherapy-in-oncology/

Series B: Frontiers in Genomics Research

Volume One: Genomics Orientations for Individualized Medicine

http://pharmaceuticalintelligence.com/biomed-e-books/genomics-orientations-for-personalized-medicine/volume-one-genomics-orientations-for-personalized-medicine/

GENOMICS related articles in the JOURNAL

Cardiovascular Pharmacogenomics – 134 articles
Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics – 55 articles
Nutrigenomics – 43 articles
Pharmacogenomics – 88 articles
Genomic Testing: Methodology for Diagnosis – 241 articles
Personalized Medicine & Genomic Research – 390 articles
Genome Biology – 421 articles

Genomics Orientations for Individualized Medicine

Volume One

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Imaging-guided cancer treatment

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, CANCER BIOLOGY & Innovations in Cancer Therapy, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Coagulation Therapy and Internal Bleeding, Components and IRB related issues, Computational Biology/Systems and Bioinformatics, CT, Disease Biology, Drug Delivery Platform Technology, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA, FDA Regulatory Affairs, Gene Regulation and Evolution, Genetics & Pharmaceutical, GLP, Health Economics and Outcomes Research, Healthcare costs and reimbursement, Human Immune System in Health and in Disease, Image Processing/Computing, Imaging-based Cancer Patient Management, Innovation in Immunology Diagnostics, ISO 14155, Medical and Population Genetics, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Medical Imaging Technology, Methods, Molecular Genetics & Pharmaceutical, MRI, Nanotechnology for Drug Delivery, Nuclear Medicine, Personalized and Precision Medicine & Genomic Research, Population Health Management, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Reproductive Biology & Bio Instrumentation, Resident-cell-based, Small Molecules in Development of Therapeutic Drugs, Technology Advance Assessment of, Technology Transfer: Biotech and Pharmaceutical, Translational Research, Translational Science, Ultra Sound, tagged Biochemistry and Molecular Biology, biomarkers, breast cancer, Cancer - General, Cancer research, Cell Biology, Chemotherapy, clinical imaging, Clinical trial, Clinical Trials, Conditions and Diseases, DNA, DNA Sequencing, gene, gene expression, genetics, health, imaging guided therapy, Lung cancer, Magnetic resonance imaging, mammography, medicine, Melanoma, Metabolism, Metabolomics, MRI, nanotechnology, ovarian cancer, Personalized medicine, Prostate cancer, Prostate-specific antigen, research, science, surgery, Therapy on September 30, 2014| Leave a Comment »

Imaging-guided cancer treatment

Writer & reporter: Dror Nir, PhD

It is estimated that the medical imaging market will exceed $30 billion in 2014 (FierceMedicalImaging). To put this amount in perspective; the global pharmaceutical market size for the same year is expected to be ~$1 trillion (IMS) while the global health care spending as a percentage of Gross Domestic Product (GDP) will average 10.5% globally in 2014 (Deloitte); it will reach ~$3 trillion in the USA.

Recent technology-advances, mainly miniaturization and improvement in electronic-processing components is driving increased introduction of innovative medical-imaging devices into critical nodes of major-diseases’ management pathways. Consequently, in contrast to it’s very small contribution to global health costs, medical imaging bears outstanding potential to reduce the future growth in spending on major segments in this market mainly: Drugs development and regulation (e.g. companion diagnostics and imaging surrogate markers); Disease management (e.g. non-invasive diagnosis, guided treatment and non-invasive follow-ups); and Monitoring aging-population (e.g. Imaging-based domestic sensors).

In; The Role of Medical Imaging in Personalized Medicine I discussed in length the role medical imaging assumes in drugs development. Integrating imaging into drug development processes, specifically at the early stages of drug discovery, as well as for monitoring drug delivery and the response of targeted processes to the therapy is a growing trend. A nice (and short) review highlighting the processes, opportunities, and challenges of medical imaging in new drug development is: Medical imaging in new drug clinical development.

The following is dedicated to the role of imaging in guiding treatment.

Precise treatment is a major pillar of modern medicine. An important aspect to enable accurate administration of treatment is complementing the accurate identification of the organ location that needs to be treated with a system and methods that ensure application of treatment only, or mainly to, that location. Imaging is off-course, a major component in such composite systems. Amongst the available solution, functional-imaging modalities are gaining traction. Specifically, molecular imaging (e.g. PET, MRS) allows the visual representation, characterization, and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In oncology, it can be used to depict the abnormal molecules as well as the aberrant interactions of altered molecules on which cancers depend. Being able to detect such fundamental finger-prints of cancer is key to improved matching between drugs-based treatment and disease. Moreover, imaging-based quantified monitoring of changes in tumor metabolism and its microenvironment could provide real-time non-invasive tool to predict the evolution and progression of primary tumors, as well as the development of tumor metastases.

A recent review-paper: Image-guided interventional therapy for cancer with radiotherapeutic nanoparticles nicely illustrates the role of imaging in treatment guidance through a comprehensive discussion of; Image-guided radiotherapeutic using intravenous nanoparticles for the delivery of localized radiation to solid cancer tumors.

Abstract

One of the major limitations of current cancer therapy is the inability to deliver tumoricidal agents throughout the entire tumor mass using traditional intravenous administration. Nanoparticles carrying beta-emitting therapeutic radionuclides [DN: radioactive isotops that emits electrons as part of the decay process a list of β-emitting radionuclides used in radiotherapeutic nanoparticle preparation is given in table1 of this paper.) that are delivered using advanced image-guidance have signiﬁcant potential to improve solid tumor therapy. The use of image-guidance in combination with nanoparticle carriers can improve the delivery of localized radiation to tumors. Nanoparticles labeled with certain beta-emitting radionuclides are intrinsically theranostic agents that can provide information regarding distribution and regional dosimetry within the tumor and the body. Image-guided thermal therapy results in increased uptake of intravenous nanoparticles within tumors, improving therapy. In addition, nanoparticles are ideal carriers for direct intratumoral infusion of beta-emitting radionuclides by convection enhanced delivery, permitting the delivery of localized therapeutic radiation without the requirement of the radionuclide exiting from the nanoparticle. With this approach, very high doses of radiation can be delivered to solid tumors while sparing normal organs. Recent technological developments in image-guidance, convection enhanced delivery and newly developed nanoparticles carrying beta-emitting radionuclides will be reviewed. Examples will be shown describing how this new approach has promise for the treatment of brain, head and neck, and other types of solid tumors.

The challenges this review discusses

intravenously administered drugs are inhibited in their intratumoral penetration by high interstitial pressures which prevent diffusion of drugs from the blood circulation into the tumor tissue [1–5].
relatively rapid clearance of intravenously administered drugs from the blood circulation by kidneys and liver.
drugs that do reach the solid tumor by diffusion are inhomogeneously distributed at the micro-scale – This cannot be overcome by simply administering larger systemic doses as toxicity to normal organs is generally the dose limiting factor.
even nanoparticulate drugs have poor penetration from the vascular compartment into the tumor and the nanoparticles that do penetrate are most often heterogeneously distributed

How imaging could mitigate the above mentioned challenges

The inclusion of an imaging probe during drug development can aid in determining the clearance kinetics and tissue distribution of the drug non-invasively. Such probe can also be used to determine the likelihood of the drug reaching the tumor and to what extent.

Note: Drugs that have increased accumulation within the targeted site are likely to be more effective as compared with others. In that respect, Nanoparticle-based drugs have an additional advantage over free drugs with their potential to be multifunctional carriers capable of carrying both therapeutic and diagnostic imaging probes (theranostic) in the same nanocarrier. These multifunctional nanoparticles can serve as theranostic agents and facilitate personalized treatment planning.

Imaging can also be used for localization of the tumor to improve the placement of a catheter or external device within tumors to cause cell death through thermal ablation or oxidative stress secondary to reactive oxygen species.

See the example of Vintfolide in The Role of Medical Imaging in Personalized Medicine

Note: Image guided thermal ablation methods include radiofrequency (RF) ablation, microwave ablation or high intensity focused ultrasound (HIFU). Photodynamic therapy methods using external light devices to activate photosensitizing agents can also be used to treat superﬁcial tumors or deeper tumors when used with endoscopic catheters.

Quality control during and post treatment

For example: The use of high intensity focused ultrasound (HIFU) combined with nanoparticle therapeutics: HIFU is applied to improve drug delivery and to trigger drug release from nanoparticles. Gas-bubbles are playing the role of the drug’s nano-carrier. These are used both to increase the drug transport into the cell and as ultrasound-imaging contrast material. The ultrasound is also used for processes of drug-release and ablation.

Additional example; Multifunctional nanoparticles for tracking CED (convection enhanced delivery) distribution within tumors: Nanoparticle that could serve as a carrier not only for the therapeutic radionuclides but simultaneously also for a therapeutic drug and 4 different types of imaging contrast agents including an MRI contrast agent, PET and SPECT nuclear diagnostic imaging agents and optical contrast agents as shown below. The ability to perform multiple types of imaging on the same nanoparticles will allow studies investigating the distribution and retention of nanoparticles initially in vivo using non-invasive imaging and later at the histological level using optical imaging.

Conclusions

Image-guided radiotherapeutic nanoparticles have signiﬁcant potential for solid tumor cancer therapy. The current success of this therapy in animals is most likely due to the improved accumulation, retention and dispersion of nanoparticles within solid tumor following image-guided therapies as well as the micro-ﬁeld of the β-particle which reduces the requirement of perfectly homogeneous tumor coverage. It is also possible that the intratumoral distribution of nanoparticles may beneﬁt from their uptake by intratumoral macrophages although more research is required to determine the importance of this aspect of intratumoral radionuclide nanoparticle therapy. This new approach to cancer therapy is a fertile ground for many new technological developments as well as for new understandings in the basic biology of cancer therapy. The clinical success of this approach will depend on progress in many areas of interdisciplinary research including imaging technology, nanoparticle technology, computer and robot assisted image-guided application of therapies, radiation physics and oncology. Close collaboration of a wide variety of scientists and physicians including chemists, nanotechnologists, drug delivery experts, radiation physicists, robotics and software experts, toxicologists, surgeons, imaging physicians, and oncologists will best facilitate the implementation of this novel approach to the treatment of cancer in the clinical environment. Image-guided nanoparticle therapies including those with β-emission radionuclide nanoparticles have excellent promise to significantly impact clinical cancer therapy and advance the ﬁeld of drug delivery.

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Imaging-Biomarkers; from discovery to validation

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, BioSimilars, CANCER BIOLOGY & Innovations in Cancer Therapy, Discovery process, Experimental validation, FDA Regulatory Affairs, Imaging-based Cancer Patient Management, Personalized and Precision Medicine & Genomic Research, Statistical Methods for Research Evaluation, Translational Research, Translational Science, tagged biomarkers, Cancer - General, Cancer research, histopathology, image fusion, image registation, imaging biomarkers, whole-mount histology on September 28, 2014| Leave a Comment »

Imaging-Biomarkers; from discovery to validation

Author: Dror Nir, PhD.

Preface

Recent technology advances such as miniaturization and improvement in electronic-processing components is driving increased introduction of innovative medical-imaging devices into critical nodes of major-diseases’ management pathways. Similarly, medical imaging bears outstanding potential to improve the process of drugs development and regulation (e.g. companion diagnostics and imaging surrogate markers. In; The Role of Medical Imaging in Personalized Medicine I discussed in length the role medical imaging assumes in drugs development. Integrating imaging into drug development processes, specifically at the early stages of drug discovery, as well as for monitoring drug delivery and the response of targeted processes to the therapy is a growing trend. A nice (and short) review highlighting the processes, opportunities, and challenges of medical imaging in new drug development is: Medical imaging in new drug clinical development. An important aspect of drug development that is largely discussed is facilitating testing of the new drug through clinical studies. A major hurdle in development of many anti-cancer drugs is the long time that is required to determine the efficacy of the new drug through measurement of clinically meaningful endpoints; e.g. overall survival. Imaging is offering the opportunity to determine surrogate markers of clinical outcome (as a substitute for a clinically meaningful endpoints). The need for surrogate outcome markers is especially great with newer agents that may act by tumour stabilization as opposed to shrinkage.

To comply with current trends; e.g. personalized medicine and evidence-based medicine, medical imaging must support quantification of meaningful pathological phenomena; e.g. morphological deformations, enhanced/reduced chemical reactions, presence/absence of biological substances etc….

Two examples:

Molecular imaging (e.g. PET, MRS) allows the visual representation, characterization, and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In oncology, it can be used to depict the abnormal molecules as well as the aberrant interactions of altered molecules on which cancers depend. An established biological process is neoplastic angiogenesis is associated with a number of detectable changes at molecular and microcirculatory levels. In Positron emission tomographic imaging of angiogenesis and vascular function the authors are offering that direct study of angiogenic molecular biology and tumour circulation before during and after treatment may offer useful surrogate markers for vascular-targeted therapies. The paper reviews two main areas: (a) the methodology behind PET imaging of tumour blood supply with 15O-oxygen labelled compounds; and (b) newer tracers in development as markers of angiogenetic biology.

A largely sought-for application for medical imaging is Monitoring quality of surgery: Cancer patients could benefit from a surgical procedure that helps the surgeon to determine adequate tumor resection margins. Variety of applications and work-flows; e.g. Systemic injection of tumor-specific fluorescence agents with subsequent intraoperative optical imaging to guide the surgeon in the process are offered. Recently, in order to overcome the problem of tumor heterogeneity it was proposed to shift the focus of tumor targeting towards the follicle-stimulating hormone receptor (FSHR).

Imaging bio-markers

Being able to discover and clinically validate fundamental finger-prints of cancer which can be detected and quantified through medical-imaging modalities is key to transforming the potential presented by medical imaging into clinical reality. Such specific finger-prints/characteristics are usually referred to as imaging bio-markers.

A critical step in the discovery and validation of imaging bio-markers is the matching of tissue location as depicted by imaging-products (most commonly images) to their histology, as underlined by a pathologist under the microscope.

Since histology requires extraction of organ tissue and some processing, it is impossible to achieve such matching in real time. Therefore, different techniques were developed to support the retrospective matching between histology and imaging. The most prevalent one rely on image registration: i.e. the products of medical imaging are registered to images of pathology slides. The main limitation of such methods has to do with:

The fact that the two images poses largely different image resolution.
The form-factor (shape and dimensions) of Histological tissue-slides are distorted in comparison to their in-vivo state.
Histology-reading is subjective; i.e. the concordance between readings of different pathologist is far from being satisfactory. It gets worse when it comes to staging of the cancer.
There is large variation in the quality of medical imaging products.

A Workflow to Improve the Alignment of Prostate Imaging with Whole-mount Histopathology presents a robust methodology validating imaging biomarkers in the case of prostate cancer. In this paper we describe a workflow for three-dimensional alignment of prostate imaging data against whole-mount prostatectomy reference specimens and assess its performance against a standard workflow. We hypothesized that integration of image registration principles into the histological workflow for radical prostatectomy specimens would increase the alignment accuracy. In this post I will include only few excerpts from this paper which I strongly recommend to read in full.

Materials and Methods

Ethical approval was granted. Patients underwent motorized transrectal ultrasound (Prostate Histoscanning) to generate a three-dimensional image of the prostate before radical prostatectomy. The test workflow incorporated steps for axial alignment between imaging and histology, size adjustments following formalin fixation, and use of custom-made parallel cutters and digital caliper instruments. The control workflow comprised freehand cutting and assumed homogeneous block thicknesses at the same relative angles between pathology and imaging sections. The basic requirements of image registration were incorporated within the pathological protocol.

We demonstrate that the use of a simple, custom-made tissue-planer to slice the formalin-fixed prostate results in more uniform and parallel tissue blocks than conventional freehand techniques, and increases the accuracy of image alignment. We also show that accounting for dimensional change due to formalin fixation is essential during image alignment.

Figure 1: Suggested workflow for registration of scanned histopathological data with radiological imaging

Figure 3

A sketch of the tissue cutting device is shown (A). The formalin-fixed prostate was placed on the space marked “X” on the device with its flat posterior surface facing down. With the probe in the urethra to align the AP axis with the device, the base of the gland was gently pressed onto “Y”. The probe was then removed, and a mounted microtome blade was lowered along the 4mm raised edge of the device from top to bottom to cut away the block (B). The sliced block was put aside with its apical face facing down, and the process was repeated by gently pressing the cut surface flush against the device before each cut (C). The thickness of each block was measured in 5 locations marked (D).

Results

Thirty radical prostatectomy specimens were histologically and radiologically processed, either by an alignment-optimized workflow (n = 20) or a control workflow (n = 10). The optimized workflow generated tissue blocks of heterogeneous thicknesses but with no significant drifting in the cutting plane. The control workflow resulted in significantly nonparallel blocks, accurately matching only one out of four histology blocks to their respective imaging data. The image-to-histology alignment accuracy was 20% greater in the optimized workflow (P < .0001), with higher sensitivity (85% vs. 69%) and specificity (94% vs. 73%) for margin prediction in a 5 × 5-mm grid analysis.

Figure 5. Assessment of alignment accuracy between radiological images and pathological sections

The method of assessing alignment accuracy between radiological images and pathological slides is shown using an example. Each square within the grids overlaid onto histology and radiological images were scored either as a “1”, indicating the presence of a histological or radiological margin, respectively, or “0”. Scored pathology grids were used as the reference, and scored radiology grids were used as the index. Hence, we determined true positives i.e. grid points score “1” in both histology and radiology (yellow squares, n=25), false positives i.e. grid points on the radiology scores “1” but not on histology (green squares, n=4), false negatives i.e. grid points on the histology scores “0” but not on radiology (red squares, n=3), and true negatives (grey squares, n=38).

Conclusions

A significantly better alignment was observed in the optimized workflow. Evaluation of prostate imaging biomarkers using whole-mount histology references should include a test-to-reference spatial alignment workflow.

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Archive for the ‘Personalized and Precision Medicine & Genomic Research’ Category

LIVE – Now –>> CRISPR-Cas9 Discovery and Development of Programmable Genome Engineering – Gabbay Award Lectures in Biotechnology and Medicine – Hosted by Rosenstiel Basic Medical Sciences Research Center, 10/27/14 3:30PM Brandeis University, Gerstenzang 121

REAL TIME Conference Coverage by Dr. Aviva Lev-Ari, PhD, RN

Gabbay Award Lecture in Biotechnology and Medicine @Brandeis

Second Speaker

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CRISPR Service / Cas9

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We are experts in CRISPR Service! Applied StemCell is in Nature Biotechnology as one of the select companies for CRISPR-Cas9 tools! Monya Baker, “Gene Editing at CRISPR Speed,” Nature Biotechnology, 32: 309-312, April 2014.

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Geneticist George Church: A Future Without Limits

George Church backs a startup solution to the massive gene therapy manufacturing bottleneck

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Glycosaminoglycans, Mucopolysaccharides, L-iduronidase, Enzyme Therapy

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Introduction to Metabolomics

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Editorials & Publications of Articles (Post)

in e-Books by

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Contributions of Aviva Lev-Ari, PhD, RN

Five Bilingual BioMed e-Series – 37 volumes

List of Aviva Lev-Ari’s Articles in English Edition

18 volumes in 17 e-Books

Series A: Cardiovascular Diseases

(6 books) Kindle Edition

Series B: Frontiers in Genomics Research

(2 book series) Kindle Edition

Series C: Cancer & Oncology

(2 book series) Kindle Edition

Series D: BioMedicine – Metabolomics, Immunology, Infectious

Diseases, Reproductive Genomic Endocrinology

(4 book series) Kindle Edition

Series E: Patient-Centered Medicine & Precision Medicine

(4 book series) Kindle Edition

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e-Books in Medicine

electronic Table of Contents (eTOCs) of each Volume in the SIXTEEN Volume BioMed e-Series

All 18 volumes in e-Books on the Medicine and Life Sciences shelf in Kindle Store:

Amazon’s Aviva Lev-Ari Page

36 results for Kindle Store :

English Edition: 18 Volumes in 17 e-Books

ARTICLES in e-BOOKS

Series A: e-Books on Cardiovascular Diseases

Volume One: Perspectives on Nitric Oxide

Volume Two: Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation

Volume Three: Etiologies of CVD: Epigenetics, Genetics & Genomics

Volume Four: Therapeutic Promise: CVD, Regenerative & Translational Medicine

Volume Five: Pharmaco-Therapies for CVD

Productive Collaborations among Team members: N = 24

Volume Six: Interventional Cardiology, Cardiac Surgery and Cardiovascular Imaging for Disease Diagnosis and Guidance of Treatment

Series B: e-Books on Genomics & Medicine

Volume 1: Genomics and Individualized Medicine

Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

Series C: e-Books on Cancer & Oncology

Volume One: Cancer and Genomics

Volume Two: Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery

Series D: e-Books on BioMedicine

Volume 1: Metabolic Genomics & Pharmaceutics

Volume 2 & 3: The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications

Series E:

Patient-centric Medicine

Content Consultant: Larry H Bernstein, MD, FCAP

Volume 1: The VOICES of Patients, Hospital CEOs, Health Care Providers, Care Givers and Families: Personal Experience with Critical Care and Invasive Medical Procedures

Volume 2: Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders – Conversion Format stage

Volume 3: Milestones in Physiology & Discoveries in Medicine and Genomics, on Amazon.com since 12/27/2015

Volume 4: Medical 3D BioPrinting – The Revolution in Medicine

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Mapping the Universe of Pharmaceutical Business Intelligence: The Model developed by LPBI and the Model of Best Practices LLC

We concluded that the two models are viable, represent fast growth, the models and non-competing and are in full complementarity, thus, expanding the domain and the practice of the industrial sector, aka, Pharmaceutical Business Intelligence.

Model A:

Leaders in Pharmaceutical Business Intelligence (LPBI),

Boston, Philadelphia, CT, CA and Israel

Our Business Portfolio

VENTURE #1: