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SNP-based Study on high BMI exposure confirms CVD and DM Risks – no associations with Stroke, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 1: Next Generation Sequencing (NGS)

SNP-based Study on high BMI exposure confirms CVD and DM Risks – no associations with Stroke

Reporter: Aviva Lev-Ari, PhD, RN

Genes Affirm: High BMI Carries Weighty Heart, Diabetes Risk – Mendelian randomization study adds to ‘burgeoning evidence’

by Crystal Phend, Senior Associate Editor, MedPage Today, July 05, 2017

 

The “genetically instrumented” measure of high BMI exposure — calculated based on 93 single-nucleotide polymorphisms associated with BMI in prior genome-wide association studies — was associated with the following risks (odds ratios given per standard deviation higher BMI):

  • Hypertension (OR 1.64, 95% CI 1.48-1.83)
  • Coronary heart disease (CHD; OR 1.35, 95% CI 1.09-1.69)
  • Type 2 diabetes (OR 2.53, 95% CI 2.04-3.13)
  • Systolic blood pressure (β 1.65 mm Hg, 95% CI 0.78-2.52 mm Hg)
  • Diastolic blood pressure (β 1.37 mm Hg, 95% CI 0.88-1.85 mm Hg)

However, there were no associations with stroke, Donald Lyall, PhD, of the University of Glasgow, and colleagues reported online in JAMA Cardiology.

The associations independent of age, sex, Townsend deprivation scores, alcohol intake, and smoking history were found in baseline data from 119,859 participants in the population-based U.K. Biobank who had complete medical, sociodemographic, and genetic data.

“The main advantage of an MR approach is that certain types of study bias can be minimized,” the team noted. “Because DNA is stable and randomly inherited, which helps to mitigate errors from reverse causality and confounding, genetic variation can be used as a proxy for lifetime BMI to overcome limitations such as reverse causality and confounding, a process that hampers observational analyses of obesity and its consequences.”

 

Other related articles published in this Open Access Online Scientific Journal include the following:

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    Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics

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Breakthroughs: Insights From the Personalized Medicine & Diagnostics Track at the 2017 BIO International Convention

Guest Author: David Davenport, Office Administrator, Personalized Medicine Coalition

 

“Health care today is reactive and costly … anything but personalized … but we are now entering a new era where health care is becoming proactive, preventive, highly personalized and most importantly predictive,” said J. Craig Venter, Ph.D., Founder, President, CEO, J. Craig Venter Institute, during his opening keynote at the Personalized Medicine and Diagnostics Track at the 2017 BIO International Convention in San Diego from June 21 – 22. The track, co-organized by PMC, brought together thought leaders to discuss breakthroughs in advancing personalized medicine. From those conversations several themes emerged:

Complex genetic data require a “knowledge network” to translate into personalized care.

During the session titled The Next Frontier: Navigating Clinical Adoption of Personalized Medicine, moderated by PMC Vice President for Science Policy Daryl Pritchard, Ph.D., panelists discussed how to accelerate the clinical adoption of innovative personalized therapies. Jennifer Levin Carter, M.D., Founder and Chief Medical Officer of N-of-One, a clinical diagnostic testing interpretation service company, explained that as data grows in complexity, there is a growing need for partnerships to efficiently analyze the data and develop effective targeted treatment plans. India Hook-Barnard, Ph.D., Director of Research Strategy, Associate Director of Precision Medicine, University of California, San Francisco (UCSF), agreed and discussed the need to build a “knowledge network” that can harness data and expertise to inform provider-patient decision-making.

Discussing how personalized medicine can be integrated into community health centers lacking large research budgets, Lynn Dressler, Dr.P.H., Director of Personalized Medicine and Pharmacogenomics at Mission Health Systems, a rural community health care delivery system in Asheville, North Carolina, discussed the need to better educate physicians and patients as well as the role that a knowledge network could play in providing easy and cost-effective access to diagnostic testing services.

Delivering personalized medicine requires innovative partnerships involving industry, IT companies, providers, payers and the government.

During It’s a Converging World: Innovative Partnerships and Precision Medicine, a panel moderated by Kristin Pothier, Global Head of Life Sciences Strategy, Ernst & Young, discussed the need for “open data” where improved patient care is the shared goal, and how public-private partnerships that address education, evidence development and access to care can help foster personalized medicine.

During a session titled Nevada as a New Model for Population Health Study, Nevada-based health system Renown Health outlined a study in which it partnered with genetic testing company 23andMe to examine whether free access to genetic testing changes participants’ practices in managing their own health and facilitates the utilization of personalized medicine.

In the era of personalized medicine, measuring and delivering value requires a paradigm shift from population-based to individual-based evidence.

Following a discussion on regulatory and reimbursement challenges moderated by Bruce Quinn, M.D., Ph.D., Principal, Bruce Quinn Associates, during which panelists called for the simplification of payment structures to be more consistent, more efficient and more connected to the patient market, a panel moderated by Jennifer Snow, Director of Health Policy at Xcenda, discussed how value assessment frameworks must adapt to consider the value of personalized medicine. During The Whole Picture: Consideration of Personalized Medicine in Value Assessment Frameworks, panelist Mitch Higashi, Ph.D., Vice President, Health Economics and Outcomes Research, U.S., Bristol-Myers Squibb, called for patient-centered definitions of value and advocated for the inclusion of predictive biomarkers in all value frameworks. Donna Cryer, J.D., President, CEO, Global Liver Institute, added that the “patient must be the ultimate ‘arbiter of value’” and urged “transparency” in how value assessment frameworks are used.

Noting that different assessment frameworks have different goals, Roger Longman, CEO, Real Endpoints, called for more dynamic frameworks that allow different stakeholders to “use the same criteria but weigh them differently.” The panel concluded that to advance personalized medicine, value frameworks must be meaningful, practical and predictive for patients; reflect evolving evidence needs like real-world evidence; and consider breakthrough payment structures like bundled payments.

From Promise to Practice: The Way Forward for Personalized Medicine

During the concluding session, Creating a Universal Biomarker Program, moderated by Ian Wright, Owner, Strategic Innovations LLC, on behalf of Cedars-Sinai Precision Health, panelists discussed how to make patients the point of reference for their own care, as opposed to being compared to the “normal” range of population averages in treatment decisions using biomarkers. The speakers concluded that moving in that direction requires providers to establish baselines for each patient, along with tools and metrics to facilitate the approach.

In the words of Donna Cryer, “personalized medicine is the definition of value for a patient.” With the ability to detect diseases before they even express themselves, the promise of personalized medicine has never been greater.

However, changing the health care system to improve patient access to valuable personalized medicines requires innovation and collaboration. As PMC President Edward Abrahams, Ph.D., said during his opening remarks for the track, that change

“doesn’t come easily,” but “breakthrough” discussions like these continue to move us forward.

The complete track agenda can be downloaded here.

 

SOURCE

From: <pmc@personalizedmedicinecoalition.org>

Date: Monday, July 10, 2017 at 10:51 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Breakthroughs From the 2017 BIO Convention’s PM & Dx Track

Arrhythmias Detection: Speeding Diagnosis and Treatment – New deep learning algorithm can diagnose 14 types of heart rhythm defects by sifting through hours of ECG data generated by some REMOTELY iRhythm’s wearable monitors

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 9/27/2022

Paul Ching
Paul Ching• 2nd 𝐇𝐞𝐚𝐥𝐭𝐡𝐜𝐚𝐫𝐞 𝐑𝐞𝐬𝐞𝐚𝐫𝐜𝐡 𝐄𝐱𝐩𝐞𝐫𝐭 

#ECG_Sensor_Patch

ECG sensor patch is a diagnostic tool used by the clinicians for early detection of atrial fibrillation and to ensure timely treatment for such patients. It also acts as triggering alarm for the #cardiac patient about the stress levels and thus increasing the patient compliance. With advances in device miniaturization and wireless technologies and changing consumer expectations, wearable “on-body” ECG patch devices have evolved to meet contemporary needs. The wearable patch continuously record the ECG of user, which aids in arrhythmia detection and management at the point of care. It also acts as triggering alarm for the cardiac patient about the stress levels and thus increasing the patient compliance.

𝐆𝐞𝐭 𝐈𝐧𝐝𝐮𝐬𝐭𝐫𝐲 𝐑𝐞𝐬𝐞𝐚𝐫𝐜𝐡 𝐏𝐃𝐅, 𝐂𝐥𝐢𝐜𝐤 𝐇𝐞𝐫𝐞: https://lnkd.in/dbJYWhyH

#ecg #sensor #patch #ecgsensorpatch #atrialfibrillation #heart #heartbeat #technology #medicaldevice #wearable #wearabletechnology #healthcare

@@@@

Long term, the group hopes this algorithm could be a step toward expert-level arrhythmia diagnosis for people who don’t have access to a cardiologist, as in many parts of the developing world and in other rural areas. More immediately, the algorithm could be part of a wearable device that at-risk people keep on at all times that would alert emergency services to potentially deadly heartbeat irregularities as they’re happening.

said Pranav Rajpurkar, a graduate student and co-lead author of the paper. “For example, two forms of the arrhythmia known as second-degree atrioventricular block look very similar, but one requires no treatment while the other requires immediate attention.”

To test accuracy of the algorithm, the researchers gave a group of three expert cardiologists 300 undiagnosed clips and asked them to reach a consensus about any arrhythmias present in the recordings. Working with these annotated clips, the algorithm could then predict how those cardiologists would label every second of other ECGs with which it was presented, in essence, giving a diagnosis.

http://news.stanford.edu/2017/07/06/algorithm-diagnoses-heart-arrhythmias-cardiologist-level-accuracy/

 iRhythm, maker of portable ECG devices

Image Source:

https://www-technologyreview-com.cdn.ampproject.org/c/s/www.technologyreview.com/s/608234/the-machines-are-getting-ready-to-play-doctor/amp/

Cardiologist-Level Arrhythmia Detection with Convolutional Neural Networks

We develop an algorithm which exceeds the performance of board certified cardiologists in detecting a wide range of heart arrhythmias from electrocardiograms recorded with a single-lead wearable monitor. We build a dataset with more than 500 times the number of unique patients than previously studied corpora. On this dataset, we train a 34-layer convolutional neural network which maps a sequence of ECG samples to a sequence of rhythm classes. Committees of board-certified cardiologists annotate a gold standard test set on which we compare the performance of our model to that of 6 other individual cardiologists. We exceed the average cardiologist performance in both recall (sensitivity) and precision (positive predictive value).

Subjects: Computer Vision and Pattern Recognition (cs.CV)
Cite as: arXiv:1707.01836 [cs.CV]
(or arXiv:1707.01836v1 [cs.CV] for this version)

Submission history

From: Awni Hannun [view email]
[v1] Thu, 6 Jul 2017 15:42:46 GMT (852kb,D)

SOURCE

Active Learning Applied to Patient-Adaptive Heartbeat Classification

Part of: Advances in Neural Information Processing Systems 23 (NIPS 2010)

[PDF] [BibTeX] [Supplemental]

Authors

Abstract

While clinicians can accurately identify different types of heartbeats in electrocardiograms (ECGs) from different patients, researchers have had limited success in applying supervised machine learning to the same task. The problem is made challenging by the variety of tasks, inter- and intra-patient differences, an often severe class imbalance, and the high cost of getting cardiologists to label data for individual patients. We address these difficulties using active learning to perform patient-adaptive and task-adaptive heartbeat classification. When tested on a benchmark database of cardiologist annotated ECG recordings, our method had considerably better performance than other recently proposed methods on the two primary classification tasks recommended by the Association for the Advancement of Medical Instrumentation. Additionally, our method required over 90% less patient-specific training data than the methods to which we compared it.

SOURCE

Cardiologist-Level Arrhythmia Detection With Convolutional Neural Networks

Pranav Rajpurkar*, Awni Hannun*, Masoumeh Haghpanahi, Codie Bourn, and Andrew Ng

A collaboration between Stanford University and iRhythm Technologies

https://stanfordmlgroup.github.io/projects/ecg/

JULY 6, 2017

Stanford computer scientists develop an algorithm that diagnoses heart arrhythmias with cardiologist-level accuracy

A new deep learning algorithm can diagnose 14 types of heart rhythm defects, called arrhythmias, better than cardiologists. This could speed diagnosis and improve treatment for people in rural locations.

The Machines Are Getting Ready to Play Doctor

An algorithm that spots heart arrhythmia shows how AI will revolutionize medicine—but patients must trust machines with their lives.

by Will Knight,  July 7, 2017

https://www-technologyreview-com.cdn.ampproject.org/c/s/www.technologyreview.com/s/608234/the-machines-are-getting-ready-to-play-doctor/amp/

The Dark Secret at the Heart of AI

No one really knows how the most advanced algorithms do what they do. That could be a problem.

by Will Knight, April 11, 2017

https://www.technologyreview.com/s/604087/the-dark-secret-at-the-heart-of-ai/

 

Genomic Diagnostics: Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single Molecule DNA Sequencing

Curator: Aviva Lev-Ari, PhD, RN

4.2.3

4.2.3   Genomic Diagnostics: Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single Molecule DNA Sequencing, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 4: Single Cell Genomics

This article presents Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single molecule DNA sequencing

Innovations on the CRISPR System for Gene Editing: (1) Cryo-electron microscopy-based visualization of Cas3 Enzyme Cleavage (2) New tool testing an entire genome against a CRISPR molecule to predict potential errors and interactions, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Innovations on the CRISPR System for Gene Editing: (1) Cryo-electron microscopy-based visualization of Cas3 Enzyme Cleavage (2) New tool testing an entire genome against a CRISPR molecule to predict potential errors and interactions

Curator and Reporter: Aviva Lev-Ari, PhD, RN

 

Boom in human gene editing as 20 CRISPR trials gear up

A pioneering CRISPR trial in China will be the first to try editing the genomes of cells inside the body, in an effort to eliminate cancer-causing HPV virus

https://www.newscientist.com/article/2133095-boom-in-human-gene-editing-as-20-crispr-trials-gear-up/

 

(1) Cryo-electron microscopy-based visualization of Cas3 Enzyme Cleavage

Harvard Medical School and Cornell University scientists have now generated near-atomic resolution snapshots of CRISPR that reveal key steps in its mechanism of action. The findings, published in Cell on June 29, provide the structural data necessary for efforts to improve the efficiency and accuracy of CRISPR for biomedical applications.

Through cryo-electron microscopy, the researchers describe for the first time the exact chain of events as the CRISPR complex loads target DNA and prepares it for cutting by the Cas3 enzyme. These structures reveal a process with multiple layers of error detection—a molecular redundancy that prevents unintended genomic damage, the researchers say.

 

Image Source: CRISPR forms a “seed bubble” state, which acts as an initial fail-safe mechanism to ensure that CRISPR RNA matches its target DNA. Image: Liao Lab/HMS

 

In contrast to the scalpel-like Cas9, CRISPR-Cas3 acts like a shredder that chews DNA up beyond repair. While CRISPR-Cas3 has, thus far, limited utility for precision gene editing, it is being developed as a tool to combat antibiotic-resistant strains of bacteria. A better understanding of its mechanisms may broaden the range of potential applications for CRISPR-Cas3.

In addition, all CRISPR-Cas subtypes utilize some version of an R-loop formation to detect and prepare target DNA for cleavage. The improved structural understanding of this process can now enable researchers to work toward modifying multiple types of CRISPR-Cas systems to improve their accuracy and reduce the chance of off-target effects in biomedical applications.

SOURCE

Structure Basis for Directional R-loop Formation and Substrate Handover Mechanisms in Type I CRISPR-Cas System

Yibei Xiao3

,

Min Luo3

,

Robert P. Hayes4

,

Jonathan Kim

,

Sherwin Ng

,

Fang Ding

,

Maofu Liao'Correspondence information about the author Maofu Liao

,

Ailong Ke5,'Correspondence information about the author Ailong Ke
3These authors contributed equally
4Present address: Merck & Co., 770 Sumneytown Pike, West Point, PA 19486, USA
5Lead contact
Bringing CRISPR into Focus – New study reveals key steps in CRISPR-Cas3 function at near-atomic resolution
By KEVIN JIANG
June 29, 2017
Scientists from The University of Texas at Austin may have come up with a possible solution. They’ve developed something that works like a predictive editor for CRISPR: a method for anticipating and catching the tool’s mistakes as it works, thereby allowing for the editing of disease-causing errors out of genomes.
Many forms of cancer, Huntington’s disease, and even HIV can be targeted using CRISPR. CRISPR can “correct” something that was actually right — the consequences of which can make it a dangerous mistake. One that actually causes a disease. CRISPR molecules—proteins that find and edit genes—sometimes target the wrong genes, acting more like an auto-correct feature that turns correctly spelled words into typos. Editing the wrong gene could create new problems, such as causing healthy cells to become cancerous.

“You and I differ in about 1 million spots in our genetic code,” says Ilya Finkelstein, an assistant professor in the Department of Molecular Biosciences at UT Austin and the project’s principal investigator. “Because of this genetic diversity, human gene editing will always be a custom-tailored therapy.”

Image Source: The heart of the new technique developed by Finkelstein, et al. for detecting interactions between CRISPR and off-target DNA segments is a standard next generation gene sequencing slide (a.k.a. flowcell), produced by Illumina. Image by Wikimedia user Bainscou, via Creative Commons Attribution 3.0 license
CHAMP, or Chip Hybridized Affinity Mapping Platform. The heart of the test is a standard next generation genome sequencing chip already widely used in research and medicine. Two other key elements—designs for a 3-D printed mount that holds the chip under a microscope and software the team developed for analyzing the results—are open source. As a result, other researchers can easily replicate the technique in experiments involving CRISPR.

Andy Ellington, a professor in the Department of Molecular Biosciences and vice president for research of the Applied Research Laboratories at UT Austin, is a co-author of the paper. He says this method also illustrates the unpredictable side benefits of new technologies.

“Next generation genome sequencing was invented to read genomes, but here we’ve turned the technology on its head to allow us to characterize how CRISPR interacts with genomes,” says Ellington. “Inventive folks like Ilya take new technologies and extend them into new realms.”

they found that the CRISPR molecule they tested, called Cascade, pays less attention to every third letter in a DNA sequence than to the others.

Discussion

CHAMP repurposes sequenced and discarded chips from modern next-generation Illumina sequencers for high-throughput association profiling of proteins to nucleic acids. A key difference between CHAMP and prior NGS-based approaches is that it does not require any hardware or software modifications to discontinued Illumina sequencers (Nutiu et al., 2011Tome et al., 2014Buenrostro et al., 2014). In CHAMP, all association-profiling experiments are carried out on sequenced MiSeq chips and imaged in a conventional TIRF microscope. CHAMP’s computational strategy uses phiX clusters as alignment markers to align the spatial information obtained via Illumina sequencing with the fluorescent association profiling experiments. This strategy offers three key advantages over previous approaches. First, using a conventional fluorescence microscope opens new experimental configurations, including multi-color co-localization and time-dependent kinetic experiments. The excitation and emission optics can also be readily adapted for FRET (Figure S6) and other advanced imaging modalities. Second, complete fluidic access to the chip allows addition of other protein components during a biochemical reaction. Third, the computational strategy for aligning sequencer outputs to fluorescent datasets is applicable to all modern Illumina sequencers, including the MiSeq, NextSeq, and HiSeq platforms. Indeed, we also used the CHAMP imaging and bioinformatics pipeline to regenerate, image, and spatially align the DNA clusters in a HiSeq flowcell (Figure S6), providing an avenue for massively parallel profiling of protein-nucleic acid interactions on both synthetic libraries and entire genomes. Future extensions will leverage on-chip transcription and translation (e.g., ribosome display) to facilitate high-throughput studies of RNA or peptide association landscapes. These studies will permit quantitative biophysical studies of diverse protein-nucleic acid interactions.

http://www.cell.com/cell/fulltext/S0092-8674(17)30637-2

SOURCE

Massively Parallel Biophysical Analysis of CRISPR-Cas Complexes on Next Generation Sequencing Chips

Cheulhee Jung8

,

John A. Hawkins8

,

Stephen K. Jones Jr.8

,

Yibei Xiao

,

James R. Rybarski

,

Kaylee E. Dillard

,

Jeffrey Hussmann

,

Fatema A. Saifuddin

,

Cagri A. Savran

,

Andrew D. Ellington

,

Ailong Ke

,

William H. Press

,

Ilya J. Finkelstein9,'Correspondence information about the author Ilya J. Finkelstein
8These authors contributed equally
9Lead Contact

This New Gene-Editing Technique Can Spot CRISPR’s Mistakes

New Technique Enables Safer Gene-Editing Therapy Using CRISPR

Other related articles on CRISPR published on this Open Access Online Scientific Journal include the following:

255 Articles on CRISPR

The Biologic Roles of Leptin in Metabolism, Leptin Physiology and Obesity: On the Mechanism of Action of the Hormone in Energy Balance

Reporter: Aviva Lev-Ari, PhD, RN

 

More than $140 billion is spent each year in the United States to treat obesity-related diseases, according to the CDC.

Worldwide obesity rates have doubled since 1980, and most people now live in countries where more deaths are caused by overweight and obesity than by malnourishment, according to the World Health Organization.

Treatment with leptin was approved in the United States in 2014 for use in congenital leptin deficiency as well as in an unusual syndrome of lipodystrophy, but the protein has not been readily available for clinical experiments.

These are the conclusions in a commentary published June 22 in Cell Metabolism by Harvard Medical School metabolism experts Jeffrey Flier and Eleftheria Maratos-Flier.

Flier, the HMS George Higginson Professor of Physiology and Medicine, and Maratos-Flier, HMS professor of medicine at Beth Israel Deaconess Medical Center, have made significant contributions to the understanding of the metabolism of obesity and starvation in general, and of leptin in particular.

The role for leptin as a starvation signal is now well established. [T]he physiologic role of leptin in most individuals may be limited to signaling the response to hunger or starvation, and then reversing that signal as energy stores are restored

Conclusion

“We continue to believe that healthy and lean individuals exist who resist obesity at least in part through their leptin levels, and that some individuals develop obesity because they have insufficiently elevated leptin levels or cellular resistance to leptin,” Flier said.

“But in science, belief and knowledge are two different things, and as much as we may lean toward this belief, we ought to develop evidence for this hypothesis or abandon it in favor of new potential mechanisms for the regulation of body weight,” he said.

SOURCES

Leptin’s Physiologic Role: Does the Emperor of Energy Balance Have No Clothes?

Jeffrey S. Flier'Correspondence information about the author Jeffrey S. Flier

,

Eleftheria Maratos-Flier
Publication stage: In Press Corrected Proof

Seeking evidence for anti-obesity claim – Does the Emperor Have Clothes?

Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity

Maren Leifheit-Nestler12, Nana-Maria Wagner13, Rajinikanth Gogiraju1,Michael Didié14, Stavros Konstantinides15, Gerd Hasenfuss1and Katrin Schäfer1*

J Translational Medicine: Cardiovascular, Metabolic and Lipoprotein Translation. 2013; 11:170.  http://www.translational-medicine.com/content/11/1/170

http://dx.doi.org/10.1186/1479-5876-11-170

 

Other related articles on LEPTIN published in this Open Access Online Scientific Journal include the following:

 

Leptin signaling in mediating the cardiac hypertrophy associated with obesity

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

 

Leptin and Puberty

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Pregnancy with a Leptin-Receptor Mutation

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

New Insights into mtDNA, mitochondrial proteins, aging, and metabolic control

Curator: Larry H. Bernstein, MD, FCAP

Adipocyte Derived Stroma Cells: Their Usage in Regenerative Medicine and Reprogramming into Pancreatic Beta-Like Cells

Curator: Evelina Cohn, PhD

Fat Cells Reprogrammed to Make Insulin

Curator: Larry H. Bernstein, MD, FCAP

First Haploid Human Stem Cells

Reported: Irina Robu, PhD

Most of the cells in our body are diploid, which indicate they carry two sets of chromosomes—one from each parent. So far, scientists have only succeeded in generating haploid embryonic stem cells—which comprise a single set of chromosomes in non-human mammals such as mice, rats and monkeys. Nevertheless, scientists have tried to isolate and duplicate these haploid ESCs in humans, which would allow them to work with one set of human chromosomes as opposed to a mixture from both parents.

Scientists from Hebrew from The Hebrew University of Jerusalem, Columbia University Medical Center (CUMC) and The New York Stem Cell Foundation Research Institute (NYSCF) were successful in generating a new type of embryonic stem cells that has a single copy of the human genome, instead of two copies which is typically found in normal stem cells.

This landmark was finally obtained by Ido Sagi, working as a PhD student at the Hebrew University of Jerusalem which was successful in isolating and maintaining haploid embryonic stem cells in humans. Unlike in mice, these haploid stem cells were capable to differentiate into various cell types such as brain, heart and pancreas, although holding a single set of chromosomes. Sagi and his advisor, Prof. Nissim Benvenisty showed that this new human stem cell type will play an important role in human genetic and medical research.  This new human cell type cell type will aid in understanding human development and it will make genetic screening simpler and more precise, by examining a single set of chromosomes.

Based on this research, the Technology Transfer arm of the Hebrew University, started a new company New Stem, which is developing a diagnostic kit for predicting resistance to chemotherapy treatments. By gathering a broad library of human pluripotent stem cells with various genetic makeups and mutations. The company is planning to use this kit for personalized medication and future therapeutic and reproductive products.

SOURCE

https://medicalxpress.com/news/2017-06-haploid-human-stem-cells-medical.html#jCp

Other related articles published in this Open Access Online Scientific Journal include the following:

Ido Sagi – PhD Student @HUJI, 2017 Kaye Innovation Award winner for leading research that yielded the first successful isolation and maintenance of haploid embryonic stem cells in humans.

Reporter: Aviva Lev-Ari, PhD, RN

Ido Sagi – PhD Student @HUJI, 2017 Kaye Innovation Award winner for leading research that yielded the first successful isolation and maintenance of haploid embryonic stem cells in humans.

 

 

Detecting Multiple Types of Cancer With a Single Blood Test

Reporter and Curator: Irina Robu, PhD

Monitoring cancer patients and evaluating their response to treatment can sometimes involve invasive procedures, including surgery.

The liquid biopsies have become something of a Holy Grail in cancer treatment among physicians, researchers and companies gambling big on the technology. Liquid biopsies, unlike traditional biopsies involving invasive surgery — rely on an ordinary blood draw. Developments in sequencing the human genome, permitting researchers to detect genetic mutations of cancers, have made the tests conceivable. Some 38 companies in the US alone are working on liquid biopsies by trying to analyze blood for fragments of DNA shed by dying tumor cells.

Premature research on the liquid biopsy has concentrated profoundly on patients with later-stage cancers who have suffered treatments, including chemotherapy, radiation, surgery, immunotherapy or drugs that target molecules involved in the growth, progression and spread of cancer. For cancer patients undergoing treatment, liquid biopsies could spare them some of the painful, expensive and risky tissue tumor biopsies and reduce reliance on CT scans. The tests can rapidly evaluate the efficacy of surgery or other treatment, while old-style biopsies and CT scans can still remain inconclusive as a result of scar tissue near the tumor site.

As recently as a few years ago, the liquid biopsies were hardly used except in research. At the moment, thousands of the tests are being used in clinical practices in the United States and abroad, including at the M.D. Anderson Cancer Center in Houston; the University of California, San Diego; the University of California, San Francisco; the Duke Cancer Institute and several other cancer centers.

With patients for whom physicians cannot get a tissue biopsy, the liquid biopsy could prove a safe and effective alternative that could help determine whether treatment is helping eradicate the cancer. A startup, Miroculus developed a cheap, open source device that can test blood for several types of cancer at once. The platform, called Miriam finds cancer by extracting RNA from blood and spreading it across plates that look at specific type of mRNA. The technology is then hooked up at a smartphone which sends the information to an online database and compares the microRNA found in the patient’s blood to known patterns indicating different type of cancers in the early stage and can reduce unnecessary cancer screenings.

Nevertheless, experts warn that more studies are essential to regulate the accuracy of the test, exactly which cancers it can detect, at what stages and whether it improves care or survival rates.

SOURCE

https://www.fastcompany.com/3037117/a-new-device-can-detect-multiple-types-of-cancer-with-a-single-blood-test

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356857/

Other related articles published in this Open Access Online Scientific Publishing Journal include the following:

Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood – R&D @Worcester Polytechnic Institute, Micro and Nanotechnology Lab

Reporters: Tilda Barliya, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/28/liquid-biopsy-chip-detects-an-array-of-metastatic-cancer-cell-markers-in-blood-rd-worcester-polytechnic-institute-micro-and-nanotechnology-lab/

Liquid Biopsy Assay May Predict Drug Resistance

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/11/06/liquid-biopsy-assay-may-predict-drug-resistance/

One blood sample can be tested for a comprehensive array of cancer cell biomarkers: R&D at WPI

Curator: Marzan Khan, B.Sc

https://pharmaceuticalintelligence.com/2017/01/05/one-blood-sample-can-be-tested-for-a-comprehensive-array-of-cancer-cell-biomarkers-rd-wpi

 

 

Cellular Guillotine Created for Studying Single-Cell Wound Repair

Reporter: Irina Robu, PhD

Using the century-old cutting method, it would take a researcher five hours to cut 100 cells, and by the time they were done, the cells they cut first would be well on their way to healing.

In an effort to comprehend how a single cell heal, mechanical engineer Sing Tand developed a microscopic guillotine that proficiently cuts cells into two.

Tang, who is an assistant professor of mechanical engineering at Stanford University knew that finding a way to competently slice the cell in two could lead to engineering self-healing materials and machines. In order, to efficiently slice a cell in two he developed a tool that could cut 150 cells in just over 2 minutes, and the cuts were much more standardized and synchronized in the stage of their repair process. They attained this rate by creating a scaled-up version of their tool with eight identical parallel channels that run simultaneously. Being able to efficiently study cell healing could eventually help scientists study and treat a variety of human diseases such as cancer and neurodegenerative diseases. Prior to Tang’s cellular guillotine, scientists used to slice cells by hand under a microscope using a glass needle which is a method that can lead to errors.

Tang’s method can be the Holy Grail of engineering self-healing materials and machines.

SOURCE

http://news.stanford.edu/2017/06/26/stanford-scientists-create-cellular-guillotine-studying-single-cell-wound-repair/

@PharmaceuticalIntelligence.com –  A Case Study on the LEADER in Curation of Scientific Findings

Author: Aviva Lev-Ari, PhD, RN

 

Multi-facets of the LPBI Group Intellectual Property (IP) ASSETS

 

 

 

  • Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2014/10/16/editorial-publication-of-articles-in-e-books-by-leaders-in-pharmaceutical-business-intelligence-contributions-of-larry-h-bernstein-md-fcap/

  • Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/16/editorial-publication-of-articles-in-e-books-by-leaders-in-pharmaceutical-business-intelligence-contributions-of-aviva-lev-ari-phd-rn/

 

Innovations in e-Scientific Publishing Methodology Development accomplished by LPBI Group:

A.  Methodology for Curation of Scientific Findings – implementations for

  • Multi-Auhtors Authoring Cloud-based Platform

 

  • Journal Statistics – Interdisciplinary Journal covers interfaces of six domains (Life sciences, Pharmaceuticals, Medicine, Healthcare Policy, Biotech Intelligence and Medical Devices)

Curations of Scientific Findings of peer reviewed articles in top three journals in each of the Six domain

Curations written on a multi-Authoring platform by MDs, MD/PhDs, PharmD and PhDs, all 15 years after graduation of the advanced degree program, and each has a publication list before joined my team – they write clinical and medical interpretations of the scientific frontier as evidenced in the Scientific Finding section of published articles in Cell, Nature, Science, NEJM, other top journals in these six domains.

  1. Volume: 1.3 Million eReaders, ~5,150 Scientific articles, +500 categories of Research defining the Journal Ontology, 9,500 tags, 7,300, scientific comment on the articles submitted and exchange recorded between the Scientific community and our Team members
  2. Top two articles >25,000 eReaders
  3. Clicks on two Top Authors: >551,000
  4. from NIH +3,700 hits
  5. 2250 Journal subscribers by e-mail
  6. +6,200 Biotech Executive following up on LinkedIn
  • BioMed e-Series of e-Books in Medicine – 16 Volumes in Five e-Series: Cardiovascular, Genomics, Cancer, Immunology, Patient-centered Medicine

https://www.amazon.com/s/ref=dp_byline_sr_ebooks_9?ie=UTF8&text=Aviva+Lev-Ari&search-alias=digital-text&field-author=Aviva+Lev-Ari&sort=relevancerank

  • Team expertise
  1. e-Scientific Publishing: The Competitive Advantage of a Powerhouse for Curation of Scientific Findings and Methodology Development for e-Scientific Publishing – LPBI Group, A Case in Point
  2. FIVE years of e-Scientific Publishing @pharmaceuticalintellicence.com, Top Articles by Author and by e-Views >1,000, 4/27/2012 to 4/27/2017
  3. Innovations in electronic Scientific Publishing (eSP): Case Studies in Marketing eContent, Curation Methodology, Categories of Research Functions, Interdisciplinary conceptual innovations by Cross Section of Categories, Exposure to Frontiers of Science by Real Time Press coverage of Scientific Conferences

B.  Methodology for REAL TIME Coverage of Scientific Conferences using Social Media and Real Time e-Proceedings Generation: Conferences in Biotech, Life Sciences and Medicine

  • In House Developed Methodology for Real Time Press Coverage of Biotech Top International conferences – selective  topics covered at conferences lead to NEW Curations in the Journal

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

 

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    Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery (Series C Book 2)

    May 13, 2017 | Kindle eBook

    by Larry H. Bernstein and Demet Sag
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    Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics

    Nov 28, 2015 | Kindle eBook

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    Perspectives on Nitric Oxide in Disease Mechanisms (Biomed e-Books Book 1)

    Jun 20, 2013 | Kindle eBook

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    Genomics Orientations for Personalized Medicine (Frontiers in Genomics Research Book 1)

    Nov 22, 2015 | Kindle eBook

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    Metabolic Genomics & Pharmaceutics (BioMedicine – Metabolomics, Immunology, Infectious Diseases Book 1)

    Jul 21, 2015 | Kindle eBook

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    Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics (Series E: Patient-Centered Medicine Book 3)

    Dec 26, 2015 | Kindle eBook

    by Larry H. Bernstein MD FACP and Aviva Lev-Ari PhD RN
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    Cancer Biology and Genomics for Disease Diagnosis (Series C: e-Books on Cancer & Oncology Book 1)

    Aug 10, 2015 | Kindle eBook

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    Regenerative and Translational Medicine: The Therapeutic Promise for Cardiovascular Diseases

    Dec 26, 2015 | Kindle eBook

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    Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation: The Art of Scientific & Medical Curation

    Nov 29, 2015 | Kindle eBook

    by Larry H. Bernstein MD FCAP and Aviva Lev-Ari PhD RN
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