Noam Steiner Tomer, Summer Internship, Research Assistant 1
8/11/2020
Aviva Lev-Ari, PhdD, RN, Founder & DIrector
Leaders in Pharmaceutical Business Intelligence (LPBI) Group
83 Mandalay Road
Newton, MA 02459
To Whom It May Concern:
It is my pleasure to write this letter of recommendation for Noam Steiner Tomer. Noam worked for me as a summer intern at Leaders in Pharmaceutical Business Intelligence (LPBI) Group, 6/16/2020 – 8/11/2020.
Noam approaches each day as a new opportunity to learn about curating cutting edge medical articles and learned about methodologies of data curation and data annotation for applications of Natural Language Processing for Text Analysis, and was eager to contribute his organizational and analytical skills to the research needs of LPBI. Noam is hard working and a team player, he was the first to complete his assignments and collaborated well with professionals from various fields such as Medicine and Natural Language Processing, as well as with other interns. Noam thrives when given new material or skills to explore and excels when asked to learn and own new fronties of science. I believe Noam strives to succeed and is willing and available for additional tasks and assignments as needed.
Noam’s attitude and dedication has served our organization very well. For example, he curated over 40 articles from various medical fields and extracted specific information from over 50 articles on cancer. Additionally, he curated Natural Language Processing resources for use in shaping a proof of concept pilot project to be used in LPBI Group’s business plan.
I strongly believe Noam will be an invaluable asset to any organization he joins.
Sincerely,
Aviva Lev-Ari, PhD, RN
Director & Founder
Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston, NJ, New Delhi, Palo Alto, Philadelphia, Toronto, Newark, DE
Editor-in-Chief
http://pharmaceuticalintelligence.com
e-Mail: avivalev-ari@alum.berkeley.edu
(M) 617-775-0451
https://cal.berkeley.edu/AvivaLev-Ari,PhD,RN
SkypeID: HarpPlayer83 LinkedIn Profile Twitter Profile
7/31/20
Genomics Articles Word Clouds
Article #1
Article #1: Word Cloud by NT
Article #2
Unraveling Retrograde Signaling Pathways
Article #2: Word Cloud by NT
Article #3
Genomics of Bacterial and Archaeal Viruses
Article #3: Word Cloud by NT
Article #4
Genetics and Male Endocrinology
Article #4: Word Cloud by NT
7/29/20
Cancer Articles Word Clouds
Therapeutics:
Targeting the Wnt Pathway [7.11]
https://pharmaceuticalintelligence.com/2015/04/10/targeting-the-wnt-pathway-7-11/
Diagnosis:
Targeting Cancer Neoantigens and Metabolic Change in T-cells
Imaging:
State of the art in oncologic imaging of Prostate
https://pharmaceuticalintelligence.com/2013/01/28/state-of-the-art-in-oncologic-imaging-of-prostate/
Mechanisms of Tumorigenesis:
Neuroblastoma: A review
https://pharmaceuticalintelligence.com/2013/06/01/neuroblastoma-a-review/
7/23/2020
TP & LPBI Mock Story Board
What is Natural Language Processing?
- Natural Language Processing (NLP) is using computers to analyze, manipulate, and edit text and speech data
- A powerful tool for data management and customer service
Natural Language Processing & LPBI
Natural Language Processing can be used in conjunction with LPBI’s immense amount of knowledge to create quick and custom querying solutions. Providing an efficient, comprehensive, and invaluable resource for Biomedical R&D, saving patients’ lives as a result.
Summary:
Harnessing LPBI’s knowledge and providing efficient and life-saving solutions using Natural Language Processing.
*Note: Images used in this mockup are not licensed for commercial use
Promising Example:
Using NLP, lists of driver mutations for various cancers can be created using custom parameters, providing a large repository of genes. This can be extended to other information, such as a list of drugs used to treat a particular disease and its success or any other subject imaginable.
Less Promising Example:
The creation of curated lists as described above on our end, creating another type of information that can be easily monetized as units or other frameworks. It is less promising because it would require a large amount of upfront work and constant updating and maintenance.
Discarded Example:
Integration of searching using voice in the same vein as Amazon’s Alexa. This was discarded as having the ability to use voice commands has no benefit in the context of our products.
Story Board Explanation:
The story board consists of three parts, the first can be summed up as “what is NLP and why it’s good,” the second is “what can LPBI do using NLP,” and the last is a reiteration of the second. I came up with the example of the lists/repositories after listening to Dr. Williams’ presentation on the Corona DB by Dr. David Fajgenbaum. Initially my idea was to make those lists and sell them as individual units, then I shifted my thinking to the first example. My main goal with this story board was to market LPBI and its capabilities when combined with NLP.
7/20/2020
Article Word Clouds
Recent comprehensive review on the role of ultrasound in breast cancer management
Mesothelin: An early detection biomarker for cancer (By Jack Andraka)
Biochemistry of the Coagulation Cascade and Platelet Aggregation: Nitric Oxide: Platelets, Circulatory Disorders, and Coagulation Effects
Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care
7/15/2020
Understanding the Top Down Approach to Text Processing
Article Used:
Blast crisis in myeloid leukemia and the activation of a microRNA-editing enzyme called ADAR1
Defining Blocks of Text:
Paragraphs were first defined into three categories: Abstract, Introduction, and Subject.
Example of Abstract Paragraph:
“Essentially, the scientists were able to trace a series of molecular events: First, white blood cells with a leukemia-promoting gene mutation become more sensitive to signs of inflammation. That inflammatory response activates ADAR1. Then, hyper-ADAR1 editing slows down the miRNAs known as let-7. Ultimately, this activity increases cellular regeneration, or self-renewal, turning white blood cell precursors into leukemia stem cells.”
This paragraph is categorized as abstract because it is a clear and sequential summarization of the text’s subject matter. This makes it valuable as we are able to get an understanding of the subject matter of the article even if we could only read this paragraph. The main flag for its categorization as an abstract paragraph is the use of “sequencing” or “list” words such as “essentially,” “first,” “then,” and “ultimately”. It also includes many of the most commonly recurring words in the article, but that will be covered later.
Example of Introduction Paragraph:
“Few cancer mechanisms are as devastating as the generation of cancer stem cells, which arise in leukemia from white blood cell precursors. The mechanisms of this transition have been obscure, but the consequences are all too clear. Leukemia stem cells promote an aggressive, therapy-resistant form of disease called blast crisis.”
This paragraph has background information but does not contain any information that is directly useful in understanding the discoveries described in the article. It not useful if our goal is to understand the subject matter of the article with the least amount of text to read.
Example of Subject Paragraph:
“The interferons are classified in 3 major categories, Type I (α, β, ω, ε, τ, κ, ν); Type II (γ) and Type III IFNs (λ1, λ2, λ3) (1, 9, 10). The largest IFN-gene family is the group of Type I IFNs. This family includes 14 IFNα genes, one of which is a pseudogene, resulting in the expression of 13 IFNα protein subtypes (1, 9). There are 3 distinct IFNRs that are specific for the 3 different IFN types. All Type I IFN subtypes bind to and activate the Type I IFNR, while Type II and III IFNs bind to and activate the Type II and III IFNRs, respectively (9–11). It should be noted that although all the different Type I IFNs bind to and activate the Type I IFNR, differences in binding to the receptor may account for specific responses and biological effects (9). For instance, a recent study provided evidence that direct binding of mouse IFNβ to the Ifnar1 subunit, in the absence of Ifnar2, regulates engagement of signals that control expression of genes specifically induced by IFNβ, but not IFNα (12). This recent discovery followed original observations from the 90s that revealed differential interactions between the different subunits of the Type I IFN receptor in response to IFNβ binding as compared to IFNα binding and partially explained observed differences in functional responses between different Type I IFNs (9).”
This is classified as subject paragraph because of its dense and specific information. Most of the paragraphs within the article fall into this category. This is not useful if our goal is to understand the subject matter with the least amount of text, because all of these paragraphs need to be read in order to gain an understanding of the subject matter. It is flagged as a subject paragraph because it lacks any of the sequencing words present in our abstract paragraph and does not contain as many of the most common words in the article as the abstract paragraph.
Style Tools:
The article makes use of multiple style tools in order to identify both sections of the article and types of information.
Bolded text is used for multiple purposes within the article: It is used for writing the names of cited studies, for example “Exploring the RNA World in Hematopoietic Cells Through the Lens of RNA-Binding Proteins“. To delineate the leading researcher of a study, “Maria Anna Zipeto, Ph.D“. Also to separate different parts of an article, “Background“.
Headings and Titles: These are used to the separate the text and describe subject matter of that particular section, for example “Interferons and their functions” (This is a title within the article).
Parenthesis: In addition to their most common use in adding additional information, the article uses them to delineate initialisms. For example “chronic myeloid leukemia (CML)” and “adenosine-to-inosine (A-to-I)”.
Images are used to concisely show the relationships discussed within the subject matter:
Repetition:
Repeated words or phrases can also be used to gain an understanding of the subject matter of an article. I came up with these common words and phrases through skimming the article: “ADAR1,” “ADAR1 editing,” “Leukemia stem cell/ stem cell,” and “microRNA” among others. Calling back to the previous section about categorizing paragraphs, we can see that all of these common words are present in the abstract paragraph and not present in the others. This gives us a possible criteria to find abstract paragraphs, we can find the paragraphs which contain the greatest number of common words and phrases from our list.
This can be shown in the form of a word cloud:
It is important to note that while the most common words I manually picked are present, they are not in context; meaning that they are not grouped as “leukemia stem cell,” rather they are shown as “leukemia,” “stem,” and “cell”. This makes it harder to understand the subject matter from looking at the word cloud.
Formalized Table:
| Index | Word | # of occurrences |
| 0 | STAT | 94 |
| 1 | ADAR | 90 |
| 2 | cell | 69 |
| 3 | stem | 56 |
| 4 | leukemia | 50 |
| 5 | expression | 49 |
| 6 | JAK | 48 |
| 7 | IFNs | 48 |
| 8 | RNA | 40 |
| 9 | editing | 31 |
7/7/2020
Topics:
University of New South Wales NLP Dictionary:https://www.cse.unsw.edu.au/~billw/nlpdict.html
Princeton WordNet 3.1: (Thesaurus/Dictionary)
http://wordnetweb.princeton.edu/perl/webwn|https://wordnet.princeton.edu/download/current-version
Natural Language Toolkit: (NLP Python Library) https://www.nltk.org/
Glossaries:
American Cancer Society Glossary of Cancer Terms:
https://www.cancer.org/cancer/glossary.html
National Cancer Institute Genetics Glossary:
https://www.cancer.gov/publications/dictionaries/genetics-dictionary
American Medical Association Glossary of Medical Terms:
Synonyms:
- Coding and Programming
- Function and Method
- Parameters and Arguments
- Containers and Data Structures
Letters and Misspelling Matrices:
Sources: http://www.wordworkskingston.com/WordWorks/Misspelling___saycl__A_Brilliant_Mistake.html
How:
Non-word Errors – A misspelling results in the formation of a non-word (eg. errors → erros)
Real-word Errors – Misspelling results in a real word
- Typographical – (eg. there → three)
- Homophone – (eg. see → sea)
When:
All the time and everywhere
Why:
- Typing quickly results in missing or disordered letters
- Writing using phonetic basis (eg. saycl as opposed to cycle)
- Difference between homophones is not known
Unifying and Loss of Fine Meaning:
Sources: https://link.springer.com/chapter/10.1007/978-3-642-54789-8_1|https://www.youtube.com/watch?v=UeiUiCRchiU&list=PLLssT5z_DsK8BdawOVCCaTCO99Ya58ryR&index=3
Semantic Unification – Combining the meanings of multiple linguistic elements into an all-encompassing meaning (word meanings → meaning of sentence)
Examples of Loss of Fine Meaning:
- “Stolen paintings found by tree”
- “I saw the Rockies flying to San Francisco”
- “New hit novel written with River”
Trade-Offs in Text Processing:
Sources: https://arxiv.org/abs/1711.02295
- Quality vs. Efficiency (Time)
- Training Data Amount vs. Time
- Amount of Data vs. Time
GRADE A++ SJW
Sunitinib brings Adult Acute Lymphoblastic Leukemia (ALL) to Remission – RNA Sequencing – FLT3 Receptor Blockade
Additional Sources:
Summary:
The FLT3 gene, located at 13q12.2, codes for a protein named Tyrosine Kinase 3 (FLT3). As a part of the RTK family of proteins, it is found on on the outside of the cell and acts as a receptor for FLT3 ligand. When activated it takes part in signaling pathways controlling the proliferation and survival hematopoietic progenitor cells. These cells are the progenitors of red blood cells, platelets and white blood cells. The overactivation of FLT3 is a driving mutation in the progression of acute lymphoblastic lymphoma, which results in a large amount of abnormal immature white blood cells being formed. This crowds out other blood cells and fully formed leukocytes. Sunitinib is most commonly used for advanced stage kidney cancer, is a FLT3 receptor inhibitor. After being used to treat Dr. Lukas Wartman by his own request, it has shown the potential to treat ALL if test show that FLT3 is overactive. This has now given Pfitzer (the drug company which owns the medicine) a new and larger market to apply it to than the previous market.
Blast crisis in myeloid leukemia and the activation of a microRNA-editing enzyme called ADAR1
Additional Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742387/
Summary:
The article outlined this signaling pathway, WBC precursors with leukemia-promoting mutations become more sensitive to signs of inflammation. In response to inflammation JAK2 and BCR-ABL1 hyper-activation increase ADAR1 activity, which downregulates let-7 and upregulates LIN28B. Let-7 is an miRNA family which inhibits gene expression post-transcriptionally, it inhibits by either degrading target mRNA or binding to prevent translational initiation and elongation.
Map of Mutations observed in ALK-negative Anaplastic Large Cell Lymphoma (ALCL) aggressive form of non-Hodgkin’s Lymphoma
Additional Sources:
https://ghr.nlm.nih.gov/gene/STAT3#conditions
Summary:
This paper discussed some of the mutations attributed to driving ALK-ALCL and Peripheral T Cell Lymphomas (PTCLs). STAT3 is responsible for signaling the maturation of precursors to T and B cells. Hyper-activation leads to abnormally formed large cells which crowd out other cells. Chimeras of the NFkB2 or NCOR2 transcription factors with ROS1 or TYK2 were also found to increase STAT3 activation.
6/30/2020 – Grade: A+ (ALA)
Keywords and Mini-Curation derived from “Prostacyclin and Nitric Oxide: Adventures in Vascular Biology – A Tale of Two Mediators”: Reported by Aviva Lev-Ari, PhD, RN
COX2:
Definition: An enzyme that mediates the conversion of arachidonic acid to prostaglandins, which are inflammatory enzymes. The enzyme does this through two reactions, a cyclooxygenase reaction which converts the arachidonic acid into PG-G2, and a peroxidase reaction which makes the final product, PG-H2. The effects of COX-2 are most prevalent in the brain, kidneys, and the and reproductive tract.
Source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813081/
Lymphatic Cancer Metastasis Model
Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2016/03/02/lymphatic-cancer-metastasis-model/
Understanding the Stem Cell Niche: A Webinar by The Scientist
Reporter: Stephen J. Williams, Ph.D
Organoid Development
Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2015/10/30/organoid-development/
A Patient’s Perspective: On Open Heart Surgery from Diagnosis to Intervention to Recovery
Guest Author: Ferez S. Nallaseth, Ph.D
Pyrroloquinoline quinone (PQQ) – An Unproven Supplement
Summary:
Pyrroloquinoline quinone is a stable redox agent which has the novel trait of operating within the cell. It performs a similar role to carotenoids, but does so around proteins within the cell, whereas carotenoids perform their function at the cell membrane. It has shown ability to alter protein function and signaling pathways in vitro, but studies on supplementation within rodents and humans have shown few significant results. The only ones being the alteration of signaling pathways and some mitochondrial benefits. While it’s abilities as a redox molecule do not make it a pure antioxidant, it does play a part in the cyclical antioxidative cycle with the antioxidant glutathione. Fibroblastic cells incubated in PQQ disodium salt showed a peak 40x increase in Neural Growth Factor (NGF) production, a much larger increase than that induced by COX2. The increase in NGF production by COX2 is a product of PG-D2 and PG-E2 promoting production through CHRT2.
Arachidonic Acid:
Definition: Arachidonic Acid (ARA) is a polyunsaturated fatty acid which plays a major role in increasing the fluidity and flexibility of the cell membrane. Free ARA molecules also play roles in the function of ion channels, and the function of several receptors and enzymes via activation as well as inhibition. ARA in cell membranes undergoes a constant reacylation/deacylation cycle in order to keep the concentration of ARA in the cell membrane very low as well as to lower the rate of ARA oxidation. Metabolites from ARA oxidation are proinflammatories but do not initiate inflammation, they only contribute to it.
Source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052655/
Gamma Linolenic Acid (GLA) as a Therapeutic Tool in the Management of Glioblastoma
Authors: Eric Fine, Sefacor. Mike Briggs, Woodland Pharmaceuticals. Raphael Nir, SBH Sciences.
Curator: Aviva Lev-Ari, PhD, RN
A Concise Review of Cardiovascular Biomarkers of Hypertension
Curator: Larry H. Bernstein, MD, FCAP
Diabetic Nephropathy
Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2015/11/16/diabetic-nephropathy/
Pyrroloquinoline quinone (PQQ) – An Unproven Supplement
Curator: Larry H. Bernstein, MD, FCAP
*Note: I picked the last two articles, which have been presented in both this and the previous curation, in order to highlight the connections between the terms they were chosen for.
Essential Fatty Acids
https://pharmaceuticalintelligence.com/2014/10/26/essential-fatty-acids/
Summary:
A deficiency in Essential Fatty Acids (EFA), usually through total parenteral nutrition with mixtures lacking in EFA’s and those with malabsorption syndromes, has been shown to dermatitis and neural and visual function. Short-Chain α-linolenic acid (ALA) and Linolenic Acid (LA) are considered the only essential EFA’s to ingest since all other EFA’s can be synthesized from those two. ALA can be converted in the liver into n-3 and n-6 LCPUFA’s, omega-6 fatty acid can in turn be converted to gamma-linolenic acid, which itself can be converted into arachidonic acid. PG-H2 is synthesized from ARA, and from PG-H2 are synthesized enzymes and molecules that are absolutely essential to life: Prostacyclin, TX’s (most notably TXA2), and other PG’s.
Nitric Oxide:
Definition: Nitric Oxide (NO) is a signaling molecule that is used in almost every system in the human body. NO is synthesized in many places in the body by through many different enzymatic processes. In vasculature NO regulates vascular tone and blood flow through the activation of soluble guanylate cyclase. It is essential for platelet aggregation and plays a large role in keeping the amount of cholesterol in the endothelium low, preventing atherosclerosis. NO has been shown to be a major factor in insulin sensitivity. Within the brain, NO greatly affects cognitive function and neural plasticity, including many other functions.
Source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953417/
Clinical Trial for the Use of Nitric Oxide to Treat Severe COVID-19 Infection
Reporter and Curator: Aviva Lev-Ari, PhD, RN
IBD: Immunomodulatory Effect of Retinoic Acid – IL-23/IL-17A Axis Correlates with the Nitric Oxide Pathway
Curators: Aviva Lev-Ari, PhD, RN and Larry H. Bernstein, MD, FCAP
[Articles] Efficacy of Nitric Oxide, With or Without Continuing Antihypertensive Treatment, for Management of High Blood Pressure in Acute Strokes (ENOS): A Partial-Factorial Randomized Controlled T…
Curator: Aviva Lev-Ari, PhD, RN
Nitric Oxide Synthase Inhibitors (NOS-I)
Author: Larry H. Bernstein, MD, FCAP
Curators: Aviva Lev-Ari, PhD, RN and Stephen J. Williams, PhD
https://pharmaceuticalintelligence.com/2013/11/02/nitric-oxide-synthase-inhibitors/
New Encapsulation Agents for Delivery of Nitric Oxide Antibacterial Agent and Vasodilator
Summary:
While NO is incredibly important in biological processes, administration of NO has been difficult because of its gaseous nature. A new method using the sorption of NO within a metal-organic framework has been developed, which shows that NO delivered in this method causes a significant amount of NO to be chemisorbed and have a slow and partial release. Using iron has yielded great results, with the reduction of iron (III) to iron (II) increasing the affinity of NO molecules to the framework. This breakthrough allows the possibility to use NO administration in order to fight bacterial infections and over a longer period of time inhibit platelet aggregation in order to prevent thrombosis.
Prostacyclin:
Definition: Prostacyclin (PG-I2) is an enzyme produced by endothelial and muscular cells through the COX pathway using arachidonic acid. It is a potent vasodilator and reduces platelet aggregation. Its most common use case is in the treatment pulmonary arterial hypertension, but there has been a failure to lower mortality due to PAH using this approach.
Source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929860/
Lesson 3 Cell Signaling and Motility: G-Proteins, Signal Transduction: Curations and Articles of Reference as Supplemental Information: #TUBiol3373
Curator: Stephen J. Williams, PhD
Adipocyte Differentiation: The Effects of Hormones and Differentiation Factors
Curators: Irina Robu, PhD and Aviva Lev-Ari, PhD, RN
A Concise Review of Cardiovascular Biomarkers of Hypertension
Curator: Larry H. Bernstein, MD, FCAP
Clinical Trial for the Use of Nitric Oxide to Treat Severe COVID-19 Infection
Reporter and Curator: Aviva Lev-Ari, PhD, RN
*Note: The last two articles, which have been presented in this curation, were deliberately picked in order to highlight the connections between the terms they were chosen for.
Interaction of Nitric Oxide and Prostacyclin in Vascular Endothelium
Summary:
There is a common feature in Atherosclerosis found in the aorta, carotid, coronary and peripheral arteries. This commonality is the formation of unstable plaques susceptible to rupturing. Plaque formation is driven by a complex process involving the cells present in the intima of the artery and leukocytes. Inflammatory molecules produced in response to plaque buildup only serve to make the situation worse, as the presence of these molecules increases the amount of TGF-β, only worsening the atheroma. The key biological molecules produced by the endothelium that are involved with atherosclerosis are vasodilators (PGI2 in particular), NO, endothelium-derived-relaxing-factor (EDRF), and cardiac specific natriuretic peptides. Understanding the balancing relationship of NO, PGI2, and TXA2 is the main key to developing treatments for atherosclerosis and other conditions such as diabetes mellitus.
6/23/2020
Keywords and Mini-Curation
From this assignment I learned that many of the keywords we looked at have common connections within different body systems and ailments. For example the link between HDL (High-Density Lipoprotein) and inflammation. I also learned that even though we looked for the same keywords, everyone could show a degree of individuality through which articles they decided to read.
TXA2:
Definition: TXA2 is a lipid based eicosanoid signaling molecule that is produced by platelets. Included in the eicosanoid group of molecules are Prostaglandins (PG), Leukotrienes (LT), and Lipoxins (LX). All of these operate locally, meaning they do not travel through the bloodstream and go to other parts of the body. They are activated by G-Protein linked cell signaling pathways.
Source: https://pubchem.ncbi.nlm.nih.gov/compound/Thromboxane-A2
Actions of Hormones on the Circulation
Author and Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2015/02/17/action-of-hormones-on-the-circulation/
Diabetic Nephropathy
Author and Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2015/11/16/diabetic-nephropathy/
Summary of Signaling and Signaling Pathways
Author and Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2014/11/01/summary-of-signaling-and-signaling-pathways/
Complex Models of Signaling: Therapeutic Implications
Authors: Demitha De Mel, Cenk Suphioglu
Curator: Larry H. Bernstein, MD, FCAP
Platelets in Translational Research – Part 1
Reviewer and Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2013/10/07/platelets-in-translational-research-1
Complex Models of Signaling: Therapeutic Implications
Summary:
I learned that TXA2 is a type of thromboxane, a lipid signaling molecule. It is released by activated platelets during hemostasis, and is also a vasoconstrictor. The release of TXA2 during a hemostasis event is prompted by PLA2, which is itself activated by ETB receptors. TXA2 released from a platelet can diffuse across the membrane and activate other nearby platelets, though it has limited activity due to its short half life. The slower release of TXA2 by platelets compared to ADP smooths out its sharp concentration fluctuations.
Sepsis:
Definition: Sepsis is when chemicals released into the bloodstream to fight infection cause widespread inflammation which can lead to organ damage. Common symptoms include an elevated heart rate, fever and/or shivering, shortness of breath, and extreme pain or discomfort. Populations at higher risk for developing sepsis include those 65+ years of age, those with chronic medical conditions, those with weakened immune systems and children younger than 1 years old.
Source: https://www.cdc.gov/sepsis/what-is-sepsis.html
Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions
Author, Introduction and Summary: Justin D Pearlman, MD, PhD, FACC
Article Curator: Aviva Lev-Ari, PhD, RN
Nitric Oxide and Sepsis, Hemodynamic Collapse, and the Search for Therapeutic Options
Curator, Reporter, EAW: Larry H. Bernstein, MD, FCAP
Sepsis, Multi-organ Dysfunction Syndrome, and Septic Shock: A Conundrum of Signaling Pathways Cascading Out of Control
Author and Curator: Larry H. Bernstein, MD, FCAP
The Role of Biomarkers in the Diagnosis of Sepsis and Patient Management
Author: Larry H. Bernstein, MD, FCAP
Advanced Topics in Sepsis and the Cardiovascular System at its End Stage
Author: Larry H. Bernstein, MD, FCAP
The Role of Biomarkers in the Diagnosis of Sepsis and Patient Management
Summary:
I learned that it is important to diagnose Sepsis in its early stages in order to hasten recovery. There are several biomarkers which are looked at in order to determine if a patient has sepsis. The first is White Blood Cell Count (WBC), a patient is suspected to have sepsis if their WBC is above 12,000 cells/mL. The second is Procalcitonin (PCT), which is a peptide precursor which is involved with calcium homeostasis. Within the study, patients with sepsis have a mean of 20.6 ng/mL in comparison to 7.5 ng/mL in healthy patients. C-reactive Protein (CRP) is present in blood plasma with higher concentrations if an infection is occurring. The mean concentration for ill patients was 802 mg/L compared to 404 mg/L in healthy patients. Transthyretin (TTR) is another biomarker, with concentrations for ill and healthy patients being 87.7 mg/L and 125 mg/L respectively.
Agonist:
Definition: An agonist is a chemical which binds to receptors in order to produce a biological response. Partial agonists are also present in pharmacology, and are characterized by being less effective than full agonists. When partial agonists are in the presence of full agonists the resulting competition for receptors causes a lowered response due to the full agonist.
Source:https://www.osmosis.org/learn/Pharmacodynamics:_Agonist,_partial_agonist,_and_antagonist
Advancing Immunotherapies: Emerging Agonist and Antagonist Targets
Authors: Robert B. Stein, M.D., Ph.D., CSO, Agenus | Deborah Law, D. Phil. CSO Jounce Therapeutics, Inc. | J. Louise Lines, Research Scientist, Microbiology & Immunology, Dartmouth College
Authors: Robert B. Stein, Deborah Law, J. Louis Lines
Curator: Aviva Lev-Ari, PhD, RN
Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production, stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography
Curator: Aviva Lev-Ari, PhD, RN
Insulin Receptor – Agonists and Antagonists Agents
Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2015/12/18/insulin-receptor-agonists-and-antagonists-agents/
Adenosine Receptor Agonist Increases Plasma Homocysteine
Editor: Spring Zhou, Scientific Research Publishing
Curator: Larry H. Bernstein, MD, FCAP
High-Density Lipoprotein (HDL): An Independent Predictor of Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker for Cardiovascular Risk
Curator: Aviva Lev-Ari, PhD, RN
High-Density Lipoprotein (HDL): An Independent Predictor of Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker for Cardiovascular Risk
Summary:
I learned that High-Density Lipoprotein (HDL) plays an important role in Endothelial Function due to it being an agonist for Endothelial NOS (eNOS), which is an enzyme that produces Nitric Oxide. One study mentioned found that people with a loss-of-function mutation in the ATP-binding cassette transporter had decreased HDL levels. This caused endothelium-dependent vasodilator responses to be lacking, while those responses that were independent from the endothelium were unchanged. HDL also regulates the amount of lipids in caveolae. When in the presence of OxLDL, a cholesterol acceptor which causes disruption of eNOS and caveolae function, HDL maintains the correct amount of lipids through the provision of cholesterol ester.
Inflammation:
Definition: Inflammation is a response to trauma that is characterized by an increased production of white blood cells, swelling, and an increase in the production of cytokines. The trauma can be a bacterial or viral infection, physical trauma, or trauma due to radiation. Blood flow is increased due to the production of the vasodilator hormones bradykinin and histamine.
Source: https://www.ncbi.nlm.nih.gov/books/NBK279298/
Long-term Canakinumab Treatment Lowering Inflammation Independent of Lipid Levels for Residual Inflammatory Risk Benefit – Personalized Medicine for Recurrent MI, Strokes and Cardiovascular Death
Authors: Paul M Ridker et al.
Reporter: Aviva Lev-Ari, PhD, RN
Astrogliosis and Neuroinflammation: The Metastesis Process form Skin Melanoma to Brain Tumors
Authors: Hila Schwartz et al.
Reporter: Aviva Lev-Ari, PhD, RN
Role of Inflammation in Disease
Author: Jerome Groopman
Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2015/11/29/role-of-inflammation-in-disease/
Reducing Obesity-Related Inflammation
Authors: Michael N. Sack et al.
Curator: Larry H. Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2015/11/16/reducing-obesity-related-inflammation/
Steroids, Inflammation, and CAR-T Therapy
Authors: Lorraine I. Mckay, John A. Cidlowski
Curator: Stephen J. Williams, Ph.D.
https://pharmaceuticalintelligence.com/2015/09/14/steroids-inflammation-and-car-t-therapy/
Role of Inflammation in Disease
https://pharmaceuticalintelligence.com/2015/11/29/role-of-inflammation-in-disease/
Summary:
I learned that inflammation could have many connections to conditions ranging from ulcerative colitis to Alzheimer’s. In atherosclerosis for example, inflammation can be caused by cholesterol molecules embedding themselves into a blood vessel’s lining, ultimately leading to a higher risk of a heart attack or stroke. Diabetes causes a larger amount of IL-1 to be released, which has been shown to cause inflammation in the pancreas and reduce the production of insulin. Some health professionals tout special anti-inflammatory diets as a way to reduce almost every ailment. Others, while less receptive to the idea that inflammation is “final common pathway for pretty much all chronic diseases,” still recommend taking preventative anti-inflammatories such as aspirin and statins.
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