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Archive for the ‘Transcriptomics’ Category

Real Time Conferecence Coverage: Advancing Precision Medicine Conference Philadelphia PA November 1,2 2024  Deliverables

Curator: Stephen J. Williams, Ph.D.

Below are deliverables in form of real Time conference coverage from the Advancing Precision Medicine Confererence held this year in Philadelphia, PA.  The meeting brought together scientists and clinicians to discuss the challenges faced in implementing genomics and proteomics into precision medicine decision making workflow.  As summarized by a future release at the 2025 ASCO, there are many issues and hindrances to incorporating data obtained from sequencing to make a personalized medicine strategy.  The meeting focused on two main disease states: oncology and cardiovascular however most of  the live meeting notes are from the oncology tract.  In general it was discussed there are three areas which need to be addressed to correctly and more frequently incorporate precision medicine and genomic panel testing into clinical decision making workflow:

  1.  access to testing panels and testing methodology for both doctors and patients
  2. expert interpretation of results including algorithms needed to analyze the data
  3. more education of molecular biology and omics data and methodology in medical school to address knowledge gaps between clinicians and scientists

The issues can be summarized by a JCO report to ASCO in 2022:

 Helen Sadik, PhDDaryl Pritchard, PhD https://orcid.org/0000-0003-2675-0371 dpritchard@personalizedmedicinecoalition.orgDerry-Mae Keeling, BScFrank Policht, PhDPeter Riccelli, PhDGretta Stone, BSKira Finkel, MSPHJeff Schreier, MBA, and Susanne Munksted, MS.  Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non–Small-Cell Lung Cancer. 2022: JCO Precision Oncology; Volume 6. https://doi.org/10.1200/PO.22.00246

Personalized medicine presents new opportunities for patients with cancer. However, many patients do not receive the most effective personalized treatments because of challenges associated with integrating predictive biomarker testing into clinical care. Patients are lost at various steps along the precision oncology pathway because of operational inefficiencies, limited understanding of biomarker strategies, inappropriate testing result usage, and access barriers. We examine the impact of various clinical practice gaps associated with diagnostic testing-informed personalized medicine strategies on the treatment of advanced non–small-cell lung cancer (aNSCLC).

The authors used a  Diaceutics’ Data Repository, a multisource database including commercial and Medicare claims and laboratory data from over 500,000 patients with non–small-cell lung cancer in the United States. They  analyzed the number of patients with newly diagnosed aNSCLC who could have, but did not, benefit from a personalized treatment. The analysis was focused on identifying the gaps and at which steps during care did gaps existed which precipitated either lack of use of precision medicine testing or incorrect interpretation of results.

Their conclusions were alarming:

Most patients with aNSCLC eligible for precision oncology treatments do not benefit from them because of clinical practice gaps. This finding is likely reflective of similar gaps in other cancer types. An increased understanding of the impact of each practice gap can inform strategies to improve the delivery of precision oncology, helping to fully realize the promise of personalized medicine.

The links to the live meeting notes are given below and collection of tweets follow (please note this meeting did not have a Twitter hashtag)

Real Time Coverage Advancing Precision Medicine Annual Conference, Philadelphia PA November 1,2 2024

https://pharmaceuticalintelligence.com/2024/11/01/real-time-coverage-advancing-precision-medicine-annual-conference-philadelphia-pa-november-12-2024/

Real Time Coverage Morning Session on Precision Oncology: Advancing Precision Medicine Annual Conference, Philadelphia PA November 1 2024

https://pharmaceuticalintelligence.com/2024/11/01/real-time-coverage-morning-session-on-precision-oncology-advancing-precision-medicine-annual-conference-philadelphia-pa-november-1-2024/

Real Time Coverage Afternoon Session on Precision Oncology: Advancing Precision Medicine Annual Conference, Philadelphia PA November 1 2024

https://pharmaceuticalintelligence.com/2024/11/01/real-time-coverage-afternoon-session-on-precision-oncology-advancing-precision-medicine-annual-conference-philadelphia-pa-november-1-2024/ 

Real Time Coverage Morning Session on Precision Oncology: Advancing Precision Medicine Annual Conference, Philadelphia PA November 2 2024

https://pharmaceuticalintelligence.com/2024/11/04/real-time-coverage-morning-session-on-precision-oncology-advancing-precision-medicine-annual-conference-philadelphia-pa-november-2-2024/ 

Tweet Collection

Tweet Collection Advancing Precision Medicine Conference November 1,2 2024 Philadelphia PA

 

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Real Time Conference Coverage: Advancing Precision Medicine Conference, Afternoon Omics Session Track 2 October 3 2025

Reporter: Stephen J. Williams, PhD

Leaders in Pharmaceutical Business Intellegence will be covering this conference LIVE over X.com at

@pharma_BI

@StephenJWillia2

@AVIVA1950

@AdvancingPM

using the following meeting hashtags

#AdvancingPM #precisionmedicine #WINSYMPO2025

4:20-4:40

Andrea Ferreira-Gonzalez

 

  • APOE was marker for defining a long term survivor and short term survivor for ovarian cancer patients; the markers were in the stroma
  • there is spatial communication between tumor and underlying stroma
  • it is imperative to understand how your multiomics equipment images a tumor area before it laser captures and send to the MS system; can lose a lot of tissue and information based on differences in resolution
  • many of these multiomics systems are validated for the clinic in EU not US
  • multiomics spatial analysis allows you to image protein, metabolite, mRNA expression in the 3 dimensional environment of the tumor (tumor cells and stroma)
  • they are making a human tumor atlas
  • they say a patient who had tumor went home during COVID and took vaccine but got ill with vaccine; but came back to check tumor and tumor had greatly regressed because prevaccine the tumor was immunologically cold and post COVID vaccine any left over tumor showed great infiltration of immune cells

4:40-4:55

Andrea Ferreira-Gonzalez

Aruna Ayer, PhDVP, Multiomics, Innovation and Scientific AffairsBD Biosciences

  • BD Bioscience multiomics platform is modular and can add more omics levels in the platorm
  • for example someone wanted to look at T cells
  • people have added CRISPR screens on the omics platform
  • most people are using single cell spatial omics
  • they have a FACS on their platform too so you can look at single cell spatial omics and sort different cellular populations
  • very comparative to 10X Genomics platform
  • their proteomics is another layer you can add on their platform however with proteomics you can high background notice with spatial proteomics or a limited panel of biomarkers
  • Their OMICS Protein One panels are optimized for biology and tumor type.
  • get high quality multiomics data and proteomics data but in a 3D spatial format
  • developed Cellismo Data Visualization software tool

4:55-5:10

Andrea Ferreira-Gonzalez

Harsha Gowda, PhDSenior Principal Scientist, Director, Research & Lab Operations, Signios Bio

Signios Biosciences (Signios Bio) is the US-based arm of MedGenome, a global leader in genetic testing services, genomics research, and drug discovery solutions.

Signios Bio is a multiomics and bioinformatics company dedicated to revealing the intricate signals within biological data. We leverage the power of multiomics—integrating data from genomics, transcriptomics, proteomics, epigenomics, metabolomics, and microbiomics—to gain a comprehensive understanding of disease biology. Our AI-powered bioinformatics platform allows us to efficiently analyze these complex datasets, uncovering hidden patterns and accelerating the development of new therapies and diagnostics.

Through the integration of cutting-edge multiomics technologies, advanced bioinformatics, and the expertise of world-class scientists, we enable researchers and clinicians with comprehensive, end-to-end solutions to improve drug discovery and development and advance precision medicine.

As part of MedGenome, we have access to real-world evidence (RWE) from global research networks across the US, Europe, Asia, Africa, Middle East, and Latin America. This access enables us to work with our partners to uncover insights that can lead to new biomarkers and drug targets, ensuring that precision medicine is inclusive and effective for all.

https://www.signiosbiolcom 

  • their platform can do high throughput analysis of patient tumors (like gallbladder cancer) analyzing mutational spectrum with high dimensionality
  • they can integrate genomic and transcriptomics data to reveal multiple pathways affected in patient data
  • have used their platform to investigate spatial omics in lung cancer

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Real Time Conference Coverage: Advancing Precision Medicine Conference,Morning Session Track 1 October 3 2025

Reporter: Stephen J. Williams, PhD

Leaders in Pharmaceutical Business Intellegence will be covering this conference LIVE over X.com at

@pharma_BI

@StephenJWillia2

@AVIVA1950

@AdvancingPM

using the following meeting hashtags

#AdvancingPM #precisionmedicine #WINSYMPO2025

 

Agenda Track 1: WIN Symposium

8:40 – 9:00

Welcome and Introduction

William G Kaelin, Jr, MD

Source: https://winconsortium.org/ 

WIN was formed on the premise that we can accomplish more together than each organization can achieve working alone. We aim to improve cancer patients’ survival and quality of life. View WIN’s history and unique attributes:


Clinical trials, projects and publications

WIN members collaboratively design and carry out global studies designed to achieve breakthroughs for patients worldwide. Our distinguished Scientific Advisory Board oversees WIN studies. Current trials include:

 

 

William G Kaelin, Jr, MD

Nigel RussellFounder and CEOAdvancing Precision Medicine

William G Kaelin, Jr, MD

Christopher P. MolineauxPresident & Chief Executive OfficerLife Science Pennsylvania

Life Sciences Pennsylvania (LSPA) is the statewide trade association for the commonwealth’s life sciences industry. Founded in 1989, LSPA works to ensure Pennsylvania has a business and public policy climate that makes the commonwealth the most attractive location to open and operate a life sciences company. Our membership is comprised of organizations statewide, representing the entire ecosystem of the life sciences: research institutions, biotechnology, medical device, diagnostic, pharmaceutical, and investment entities, along with service providers who support the industry. Together, we unify Pennsylvania’s innovators to make the Commonwealth a global life sciences leader.

As president & CEO of Life Sciences Pennsylvania, Christopher Molineaux serves as the chief advocate and spokesman for the life sciences industry that calls Pennsylvania home. Molineaux oversees the strategic direction for the association, assuring Life Sciences Pennsylvania continues to be the catalyst that makes Pennsylvania the top location for life sciences companies.

Molineaux brings to Life Sciences Pennsylvania more than 25 years of experience in the bio-pharmaceutical and health care industries, with front-line experience in developing and executing strategies to navigate a shifting economic and political environment.

9:00-9:40

Keynote Lecture – WIN Consortium

Targeting the Achilles’ Heel of Cancer: Synthetic Lethality and Hypoxia in Precision Oncology

William Kaelin was born in New York City. He studied chemistry and mathematics at Duke University in Durham, North Carolina, and received his doctor of medicine degree there in 1982. He then did his residency at Johns Hopkins University in Baltimore, Maryland. In 2002 he became a professor at Harvard Medical School in Cambridge, Massachusetts.

Work

 

Animals need oxygen for the conversion of food into useful energy. The importance of oxygen has been understood for centuries, but how cells adapt to changes in levels of oxygen has long been unknown. William Kaelin, Peter Ratcliffe, and Gregg Semenza discovered how cells can sense and adapt to changing oxygen availability. During the 1990s they identified a molecular machinery that regulates the activity of genes in response to varying levels of oxygen. The discoveries may lead to new treatments of anemia, cancer and many other diseases.

To cite this section
MLA style: William G. Kaelin Jr – Facts – 2019. NobelPrize.org. Nobel Prize Outreach 2025. Fri. 3 Oct 2025. <https://www.nobelprize.org/prizes/medicine/2019/kaelin/facts/>

From his Nobel award ceremony:

Gregg Semenza and Sir Peter Ratcliffe decided, independently, to find out how the erythropoietin gene can have such an extraordinary ability to react when oxygen levels drop. Semenza discovered an essential DNA element. Ratcliffe was on the same track and they showed that the element is active in all cells. Oxygen sensing thus takes place everywhere in our bodies. Semenza then discovered the critical player that acti- vates our defense genes. It was named HIF. HIF was subjected to an advanced form of control. It is continuously produced, but when oxygen is ample, it disappears. Only when oxygen levels drop, HIF will remain and can mobilise our defense.

William Kaelin studied a different problem, von Hippel- Lindau disease, with inherited increased risk of certain types of cancer. Cancer cells without the gene, VHL, had activated genes normally controlled by HIF. Sir Peter Ratcliffe proved, in a crucial experiment, that VHL is required for HIF to be removed.

But what was the signal to VHL that HIF needs to disappear?
In the early 2000s, Kaelin and Ratcliffe both solved this mystery. The signal was formed by attaching oxygen atoms onto HIF.
Without oxygen, no signal to VHL, HIF is left intact and can activate our defense.

Piece by piece of the puzzle, the Laureates explained a sensitive machinery that compensates when the vital oxygen is not available in exactly the right amount.

Today we know that the machinery affects a vast range of functions.
When oxygen is lacking, oxygen transport is enhanced by generation of new blood vessels and red blood cells. Our cells are also instructed to economize with the oxygen available, by reprogramming their energy metabolism. Oxygen sensing is also involved in many diseases. As a result of the Laureates’ discoveries, intense activities are under way to develop treatments against for example anemia and cancer.

Professors Semenza, Ratcliffe and Kaelin,
Your groundbreaking discoveries have shed light on a beautiful mechanism explaining our ability to sense and react to fluctuating oxygen levels. The system you have clarified is of fundamental importance for all aspects of physiology and for many human diseases. Without it, animal life would not be possible on this planet.

On behalf of the Nobel Assembly at Karolinska Institutet, it is my great privilege to convey to you our warmest congratulations. I now ask you to step forward to receive the Nobel Prize from the hands of His Majesty the King.

TRACK 1  204BC

 

WIN SYMPOSIUM

MULTI-OMICS

9:40 – 10:40

SESSION 1

From Base Pairs To Better Care:

AI and Omics in Precision Oncology

9:40-10:00

Multi-Omic Profiling and Clinical Decision Support in Precision Oncology

Andrea Ferreira-Gonzalez

David Spetzler, PhD, MBA, MS,  President, Caris Life Sciences

10:00-10:20

Integrating Omics and AI for Next-Gen Precision Oncology

Andrea Ferreira-Gonzalez

Keith T. Flaherty, MD, FAACR, Director of Clinical Research, Massachusetts General Cancer CenterProfessor of Medicine, Harvard Medical School;
President-Elect: 2025-2026, American Association for Cancer Research (AACR) 

10:20-10:40

Real-World Data and AI in Precision Oncology: Making Data Work for Patients – Q&A

Andrea Ferreira-Gonzalez

MODERATOR: Jeff Elton, PhD, Vice Chairman, Founding CEO
ConcertAI

Andrea Ferreira-Gonzalez

PANELISTS: David Spetzler, PhD, MBA, MS, President, Caris Life Sciences

Andrea Ferreira-Gonzalez

Keith T. Flaherty, MD, FAACR, Director of Clinical Research, Massachusetts General Cancer CenterProfessor of Medicine, Harvard Medical School;
President-Elect: 2025-2026, American Association for Cancer Research (AACR) 

0:40 – 11:10

Break and Exhibits

TRACK 1  204BC

TRACK 2  204A

WIN SYMPOSIUM

MULTI-OMICS

11:10 – 1:10

SESSION 2

The Evolution of Precision Oncology:

Integrating MRD, AI, and Beyond

11:10-12:00

Precision Cancer Consortium

Andrea Ferreira-Gonzalez
Andrea Ferreira-Gonzalez

Shruti Mathur, MSPharma Diagnostic Strategy Leader, Global Product Strategy (GPS), Genentech

Andrea Ferreira-Gonzalez

Daryl Pritchard, PhD, Interim President, Personalized Medicine Coalition

Andrea Ferreira-Gonzalez

Keith T. Flaherty, MD, FAACR, Director of Clinical Research, Massachusetts General Cancer CenterProfessor of Medicine, Harvard Medical School;
President-Elect: 2025-2026, American Association for Cancer Research (AACR) 

SESSION 3

The Shifting Landscape:

Tumor Plasticity and Resistance

12:00-12:20

Mathematical and Evolutionary Modeling in Precision Radiation Oncology

Andrea Ferreira-Gonzalez

Jacob Scott, MD, DPhil, Professor and Staff Physician-Scientist, CWRU School of Medicine and Cleveland Clinic

12:20-12:40

Plasticity and Persistence: The Role of EMT in Cancer Progression and Therapy Resistance

Andrea Ferreira-Gonzalez

Sendurai A. Mani, PhD, Professor of Pathology and Laboratory Medicine, Brown University; Associate Director of Translational Oncology, Brown University Legorreta Cancer Center

12:40-1:00

Targeting Molecularly Defined Subsets: Challenges in Translational Oncology

Andrea Ferreira-Gonzalez

Benedito A. Carneiro, MD, MS, Director, Clinical Research
Director, Cancer Drug Development; Associate Director, Division of Hematology/Oncology
Legorreta Cancer Center, Brown University Health

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Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

Curators:

 

THE VOICE of Aviva Lev-Ari, PhD, RN

In this curation we wish to present two breaking through goals:

Goal 1:

Exposition of a new direction of research leading to a more comprehensive understanding of Metabolic Dysfunctional Diseases that are implicated in effecting the emergence of the two leading causes of human mortality in the World in 2023: (a) Cardiovascular Diseases, and (b) Cancer

Goal 2:

Development of Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics for these eight subcellular causes of chronic metabolic diseases. It is anticipated that it will have a potential impact on the future of Pharmaceuticals to be used, a change from the present time current treatment protocols for Metabolic Dysfunctional Diseases.

According to Dr. Robert Lustig, M.D, an American pediatric endocrinologist. He is Professor emeritus of Pediatrics in the Division of Endocrinology at the University of California, San Francisco, where he specialized in neuroendocrinology and childhood obesity, there are eight subcellular pathologies that drive chronic metabolic diseases.

These eight subcellular pathologies can’t be measured at present time.

In this curation we will attempt to explore methods of measurement for each of these eight pathologies by harnessing the promise of the emerging field known as Bioelectronics.

Unmeasurable eight subcellular pathologies that drive chronic metabolic diseases

  1. Glycation
  2. Oxidative Stress
  3. Mitochondrial dysfunction [beta-oxidation Ac CoA malonyl fatty acid]
  4. Insulin resistance/sensitive [more important than BMI], known as a driver to cancer development
  5. Membrane instability
  6. Inflammation in the gut [mucin layer and tight junctions]
  7. Epigenetics/Methylation
  8. Autophagy [AMPKbeta1 improvement in health span]

Diseases that are not Diseases: no drugs for them, only diet modification will help

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

 

Exercise will not undo Unhealthy Diet

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

 

These eight Subcellular Pathologies driving Chronic Metabolic Diseases are becoming our focus for exploration of the promise of Bioelectronics for two pursuits:

  1. Will Bioelectronics be deemed helpful in measurement of each of the eight pathological processes that underlie and that drive the chronic metabolic syndrome(s) and disease(s)?
  2. IF we will be able to suggest new measurements to currently unmeasurable health harming processes THEN we will attempt to conceptualize new therapeutic targets and new modalities for therapeutics delivery – WE ARE HOPEFUL

In the Bioelecronics domain we are inspired by the work of the following three research sources:

  1. Biological and Biomedical Electrical Engineering (B2E2) at Cornell University, School of Engineering https://www.engineering.cornell.edu/bio-electrical-engineering-0
  2. Bioelectronics Group at MIT https://bioelectronics.mit.edu/
  3. The work of Michael Levin @Tufts, The Levin Lab
Michael Levin is an American developmental and synthetic biologist at Tufts University, where he is the Vannevar Bush Distinguished Professor. Levin is a director of the Allen Discovery Center at Tufts University and Tufts Center for Regenerative and Developmental Biology. Wikipedia
Born: 1969 (age 54 years), Moscow, Russia
Education: Harvard University (1992–1996), Tufts University (1988–1992)
Affiliation: University of Cape Town
Research interests: Allergy, Immunology, Cross Cultural Communication
Awards: Cozzarelli prize (2020)
Doctoral advisor: Clifford Tabin
Most recent 20 Publications by Michael Levin, PhD
SOURCE
SCHOLARLY ARTICLE
The nonlinearity of regulation in biological networks
1 Dec 2023npj Systems Biology and Applications9(1)
Co-authorsManicka S, Johnson K, Levin M
SCHOLARLY ARTICLE
Toward an ethics of autopoietic technology: Stress, care, and intelligence
1 Sep 2023BioSystems231
Co-authorsWitkowski O, Doctor T, Solomonova E
SCHOLARLY ARTICLE
Closing the Loop on Morphogenesis: A Mathematical Model of Morphogenesis by Closed-Loop Reaction-Diffusion
14 Aug 2023Frontiers in Cell and Developmental Biology11:1087650
Co-authorsGrodstein J, McMillen P, Levin M
SCHOLARLY ARTICLE
30 Jul 2023Biochim Biophys Acta Gen Subj1867(10):130440
Co-authorsCervera J, Levin M, Mafe S
SCHOLARLY ARTICLE
Regulative development as a model for origin of life and artificial life studies
1 Jul 2023BioSystems229
Co-authorsFields C, Levin M
SCHOLARLY ARTICLE
The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences
1 Jul 2023International Journal of Molecular Sciences24(13)
Co-authorsMasuelli S, Real S, McMillen P
SCHOLARLY ARTICLE
Bioelectricidad en agregados multicelulares de células no excitables- modelos biofísicos
Jun 2023Revista Española de Física32(2)
Co-authorsCervera J, Levin M, Mafé S
SCHOLARLY ARTICLE
Bioelectricity: A Multifaceted Discipline, and a Multifaceted Issue!
1 Jun 2023Bioelectricity5(2):75
Co-authorsDjamgoz MBA, Levin M
SCHOLARLY ARTICLE
Control Flow in Active Inference Systems – Part I: Classical and Quantum Formulations of Active Inference
1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):235-245
Co-authorsFields C, Fabrocini F, Friston K
SCHOLARLY ARTICLE
Control Flow in Active Inference Systems – Part II: Tensor Networks as General Models of Control Flow
1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):246-256
Co-authorsFields C, Fabrocini F, Friston K
SCHOLARLY ARTICLE
Darwin’s agential materials: evolutionary implications of multiscale competency in developmental biology
1 Jun 2023Cellular and Molecular Life Sciences80(6)
Co-authorsLevin M
SCHOLARLY ARTICLE
Morphoceuticals: Perspectives for discovery of drugs targeting anatomical control mechanisms in regenerative medicine, cancer and aging
1 Jun 2023Drug Discovery Today28(6)
Co-authorsPio-Lopez L, Levin M
SCHOLARLY ARTICLE
Cellular signaling pathways as plastic, proto-cognitive systems: Implications for biomedicine
12 May 2023Patterns4(5)
Co-authorsMathews J, Chang A, Devlin L
SCHOLARLY ARTICLE
Making and breaking symmetries in mind and life
14 Apr 2023Interface Focus13(3)
Co-authorsSafron A, Sakthivadivel DAR, Sheikhbahaee Z
SCHOLARLY ARTICLE
The scaling of goals from cellular to anatomical homeostasis: an evolutionary simulation, experiment and analysis
14 Apr 2023Interface Focus13(3)
Co-authorsPio-Lopez L, Bischof J, LaPalme JV
SCHOLARLY ARTICLE
The collective intelligence of evolution and development
Apr 2023Collective Intelligence2(2):263391372311683SAGE Publications
Co-authorsWatson R, Levin M
SCHOLARLY ARTICLE
Bioelectricity of non-excitable cells and multicellular pattern memories: Biophysical modeling
13 Mar 2023Physics Reports1004:1-31
Co-authorsCervera J, Levin M, Mafe S
SCHOLARLY ARTICLE
There’s Plenty of Room Right Here: Biological Systems as Evolved, Overloaded, Multi-Scale Machines
1 Mar 2023Biomimetics8(1)
Co-authorsBongard J, Levin M
SCHOLARLY ARTICLE
Transplantation of fragments from different planaria: A bioelectrical model for head regeneration
7 Feb 2023Journal of Theoretical Biology558
Co-authorsCervera J, Manzanares JA, Levin M
SCHOLARLY ARTICLE
Bioelectric networks: the cognitive glue enabling evolutionary scaling from physiology to mind
1 Jan 2023Animal Cognition
Co-authorsLevin M
SCHOLARLY ARTICLE
Biological Robots: Perspectives on an Emerging Interdisciplinary Field
1 Jan 2023Soft Robotics
Co-authorsBlackiston D, Kriegman S, Bongard J
SCHOLARLY ARTICLE
Cellular Competency during Development Alters Evolutionary Dynamics in an Artificial Embryogeny Model
1 Jan 2023Entropy25(1)
Co-authorsShreesha L, Levin M
5

5 total citations on Dimensions.

Article has an altmetric score of 16
SCHOLARLY ARTICLE
1 Jan 2023BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY138(1):141
Co-authorsClawson WP, Levin M
SCHOLARLY ARTICLE
Future medicine: from molecular pathways to the collective intelligence of the body
1 Jan 2023Trends in Molecular Medicine
Co-authorsLagasse E, Levin M

THE VOICE of Dr. Justin D. Pearlman, MD, PhD, FACC

PENDING

THE VOICE of  Stephen J. Williams, PhD

Ten TakeAway Points of Dr. Lustig’s talk on role of diet on the incidence of Type II Diabetes

 

  1. 25% of US children have fatty liver
  2. Type II diabetes can be manifested from fatty live with 151 million  people worldwide affected moving up to 568 million in 7 years
  3. A common myth is diabetes due to overweight condition driving the metabolic disease
  4. There is a trend of ‘lean’ diabetes or diabetes in lean people, therefore body mass index not a reliable biomarker for risk for diabetes
  5. Thirty percent of ‘obese’ people just have high subcutaneous fat.  the visceral fat is more problematic
  6. there are people who are ‘fat’ but insulin sensitive while have growth hormone receptor defects.  Points to other issues related to metabolic state other than insulin and potentially the insulin like growth factors
  7. At any BMI some patients are insulin sensitive while some resistant
  8. Visceral fat accumulation may be more due to chronic stress condition
  9. Fructose can decrease liver mitochondrial function
  10. A methionine and choline deficient diet can lead to rapid NASH development

 

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Bipolar Disorder now understood by Markers Identified of the Gene Expression for this Diagnosis

Reporter: Aviva Lev-Ari, PhD, RN

Published: 

Amygdala and anterior cingulate transcriptomes from individuals with bipolar disorder reveal downregulated neuroimmune and synaptic pathways

Abstract

Recent genetic studies have identified variants associated with bipolar disorder (BD), but it remains unclear how brain gene expression is altered in BD and how genetic risk for BD may contribute to these alterations. Here, we obtained transcriptomes from subgenual anterior cingulate cortex and amygdala samples from post-mortem brains of individuals with BD and neurotypical controls, including 511 total samples from 295 unique donors. We examined differential gene expression between cases and controls and the transcriptional effects of BD-associated genetic variants. We found two coexpressed modules that were associated with transcriptional changes in BD: one enriched for immune and inflammatory genes and the other with genes related to the postsynaptic membrane. Over 50% of BD genome-wide significant loci contained significant expression quantitative trait loci (QTL) (eQTL), and these data converged on several individual genes, including SCN2A and GRIN2A. Thus, these data implicate specific genes and pathways that may contribute to the pathology of BP.

SOURCE

https://www.nature.com/articles/s41593-022-01024-6

Gene Expression Markers for Bipolar Disorder Pinpointed

The work was led by researchers at Johns Hopkins’ Lieber Institute for Brain Development. The findings, published this week in Nature Neuroscience, represent the first time that researchers have been able to apply large-scale genetic research to brain samples from hundreds of patients with bipolar disorder (BD). They used 511 total samples from 295 unique donors.

“This is the first deep dive into the molecular biology of the brain in people who died with bipolar disorder—studying actual genes, not urine, blood or skin samples,” said Thomas Hyde of the Lieber Institute and a lead author of the paper. “If we can figure out the mechanisms behind BD, if we can figure out what’s wrong in the brain, then we can begin to develop new targeted treatments of what has long been a mysterious condition.”

Bipolar disorder is characterized by extreme mood swings, with episodes of mania alternating with episodes of depression. It usually emerges in people in their 20s and 30s and remains with them for life. This condition affects approximately 2.8% of the adult American population, or about 7 million people. Patients face higher rates of suicide, poorer quality of life, and lower productivity than the general population. Some estimates put the annual cost of the condition in the U.S. alone at $219.1 billion.

While drugs can be useful in treating BD, many patients find they have bothersome side effects, and for some patients, current medications don’t work at all.

In this study, researchers measured levels of messenger RNA in the brain samples. They observed almost eight times more differentially expressed gene features in the sACC versus the amygdala, suggesting that the sACC may play an especially prominent role—both in mood regulation in general and BD specifically.

In patients who died with BD, the researchers found abnormalities in two families of genes: one containing genes related to the synapse and the second related to immune and inflammatory function.

“There finally is a study using modern technology and our current understanding of genetics to uncover how the brain is doing,” Hyde said. “We know that BD tends to run in families, and there is strong evidence that there are inherited genetic abnormalities that put an individual at risk for bipolar disorder. Unlike diseases such as sickle-cell anemia, bipolar disorder does not result from a single genetic abnormality. Rather, most patients have inherited a group of variants spread across a number of genes.”

“Bipolar disorder, also known as manic-depressive disorder, is a highly damaging and paradoxical condition,” said Daniel R. Weinberger, chief executive and director of the Lieber Institute and a co-author of the study. “It can make people very productive so they can lead countries and companies, but it can also hurl them into the meat grinder of dysfunction and depression. Patients with BD may live on two hours of sleep a night, saving the world with their abundance of energy, and then become so self-destructive that they spend their family’s fortune in a week and lose all friends as they spiral downward. Bipolar disorder also has some shared genetic links to other psychiatric disorders, such as schizophrenia, and is implicated in overuse of drugs and alcohol.”

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CRISPR-Cas9 and the Power of Butterfly Gene Editing

Reporter: Madison Davis

Genome editing is a relatively new branch of genetic engineering that utilizes modern technologies in altering, inserting, or deleting selective DNA sequences within cells.  CRISPR-Cas9, otherwise known as “Clustered Regularly Interspaced Short Palindromic Repeat”, is a groundbreaking genome editing technique for scientists, as it is more efficient and allows for more precise genome changes at less of a cost in comparison to other editing methods.  The CRISPR-Cas9 procedure chiefly involves two biological molecules: an enzyme known as “Cas9” whose role is to cut the DNA during transcription, and a guide RNA molecule located within the Cas9 enzyme.  

The process of extracting and editing certain segments of DNA begins with identifying the respective segment of DNA to edit, typically around twenty nucleotides in length but can vary depending on the goal of the scientists.  This selection process can be based on prior knowledge of gene mapping sequences or random experimentation.  Upon identifying the segment, scientists will manually formulate a guide RNA molecule that matches the sequence of nucleotides found in the DNA sequence.  This gRNA molecule will then be placed in empty Cas9 enzymes.  Through the process of transcription, Cas9 enzymes will find and cut out the designated DNA sequence, where scientists are then able to insert, delete, or modify certain sequences by hand under high-definition microscopes.  

The usage of CRISPR can range from identifying tumor suppressor genes to gene mapping for species.  In recent years, it has been used more specifically to understand the evolutionary genetics behind butterfly wing patterns.  Butterfly wings are constructed from two separate layers that contain thousands of individual scales made of a hard protein called chitin.  Each individual scale contains embedded structures and pigments that reflect or absorb certain colors of light depending on their wavelengths.  Their unique structures allows certain butterfly species to exhibit wide ranges of color variation.  All together, these scales can act as identification, insulation, and camouflage. 

Through selective processing, scientists were able to identify how a loss in a certain genetic sequence labeled WntA results in a reduction in CSS (Central Symmetry Systems) and pattern boundaries, resulting in more abstract wing patterns.  A research expedition led by Anyi Mazo-Vargas experimented on two species, Heliconius erato demophoon and Heliconius sara sara.  Each butterfly wing pair composed of mainly black pigment with two main stripe patterns consisting of red and yellow and blue and white for each species, respectively.  When the WntA gene was removed in offspring, there was an increase in color pigment in areas that were previously black scales.   For instance, in Heliconius erato demophoon, there appeared to be more blurred red and yellow pigment rather than distinct colored stripe patterns.  The WntA gene was also experimented in monarch butterflies, where an absence in WnTA genes caused the initially black tipped-scales of the monarch wings to become a whiter, “bleached” pigment.

While efficient in scale, CRISPR-Cas9 editing system is often riddled with mosaic mutations, which can be a challenge in making valid conclusions in gene editing.  Mosaicism is a process of gene editing that results in an individual having multiple cells with different DNA sequences.  Not all cells of a singular individual contain the same genetic code.  When editing genetic sequences during the larva stage, not all subsequent cells are affected by such a change, and thus changes in butterfly wings can only be partially identified.  As CRISPR and other gene editing technologies continue to evolve, scientists should try to increase the accuracy of their experiments, such as editing genes in earlier germline cells or varying their experiments on more subspecies for more data analysis. 

 

SOURCES

“What Are Genome Editing and CRISPR-Cas9? – Genetics Home Reference – NIH.” U.S. National Library of Medicine, National Institutes of Health, 17 Aug. 2020, ghr.nlm.nih.gov/primer/genomicresearch/genomeediting.

Pak, Ekaterina. “CRISPR: A Game-Changing Genetic Engineering Technique.” Science in the News, 31 July 2014, sitn.hms.harvard.edu/flash/2014/crispr-a-game-changing-genetic-engineering-technique/.

Mazo-Vargas, A., Concha, C., Livraghi, L., Massardo, D., Wallbank, R., Zhang, L., Papador, J., Martinez-Najera, D., Jiggins, C., Kronforst, M., Breuker, C., Reed, R., Patel, N., McMillan, W. and Martin, A., 2020. Macroevolutionary Shifts Of Wnta Function Potentiate Butterfly Wing-Pattern Diversity. [online] PNAS. Available at: https://www.pnas.org/content/114/40/10701 [Accessed 20 August 2020].

Mehravar, Maryam, et al. “Mosaicism in CRISPR/Cas9-Mediated Genome Editing.” Developmental Biology, Academic Press, 22 Oct. 2018, www.sciencedirect.com/science/article/pii/S0012160618302513.

https://pharmaceuticalintelligence.com/2020/08/29/prime-editing-as-a-new-crispr-tool-to-enhance-precision-and-versatility/

 

 

CAST – Alternative to CRISPR/Cas9 3
Select CRISPR alternative for editing genes without cuttingCRISPR alternative for editing genes without cutting3
Select CRISPR applied to Human Germ LineCRISPR applied to Human Germ Line66
Select CRISPR/Cas9 & Gene EditingCRISPR/Cas9 & Gene Editing5
Select Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integrationTransposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration
3

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Single-cell RNA-seq helps in finding intra-tumoral heterogeneity in pancreatic cancer

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

4.3.6

4.3.6  Single-cell RNA-seq helps in finding intra-tumoral heterogeneity in pancreatic cancer, 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

Pancreatic cancer is a significant cause of cancer mortality; therefore, the development of early diagnostic strategies and effective treatment is essential. Improvements in imaging technology, as well as use of biomarkers are changing the way that pancreas cancer is diagnosed and staged. Although progress in treatment for pancreas cancer has been incremental, development of combination therapies involving both chemotherapeutic and biologic agents is ongoing.

Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (PDAC) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease.

The immune system varies in cell types, states, and locations. The complex networks, interactions, and responses of immune cells produce diverse cellular ecosystems composed of multiple cell types, accompanied by genetic diversity in antigen receptors. Within this ecosystem, innate and adaptive immune cells maintain and protect tissue function, integrity, and homeostasis upon changes in functional demands and diverse insults. Characterizing this inherent complexity requires studies at single-cell resolution. Recent advances such as massively parallel single-cell RNA sequencing and sophisticated computational methods are catalyzing a revolution in our understanding of immunology.

PDAC is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. In the present study to comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, single-cell RNA-seq (scRNA-seq) was employed to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases. The diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, were identified in PDAC.

The researchers found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, it was found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, the findings provided a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.

References:

https://www.ncbi.nlm.nih.gov/pubmed/31273297

https://www.ncbi.nlm.nih.gov/pubmed/21491194

https://www.ncbi.nlm.nih.gov/pubmed/27444064

https://www.ncbi.nlm.nih.gov/pubmed/28983043

https://www.ncbi.nlm.nih.gov/pubmed/24976721

https://www.ncbi.nlm.nih.gov/pubmed/27693023

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Real Time Coverage @BIOConvention #BIO2019: Precision Medicine Beyond Oncology June 5 Philadelphia PA

Reporter: Stephen J Williams PhD @StephenJWillia2

Precision Medicine has helped transform cancer care from one-size-fits-all chemotherapy to a new era, where patients’ tumors can be analyzed and therapy selected based on their genetic makeup. Until now, however, precision medicine’s impact has been far less in other therapeutic areas, many of which are ripe for transformation. Efforts are underway to bring the successes of precision medicine to neurology, immunology, ophthalmology, and other areas. This move raises key questions of how the lessons learned in oncology can be used to advance precision medicine in other fields, what types of data and tools will be important to personalizing treatment in these areas, and what sorts of partnerships and payer initiatives will be needed to support these approaches and their ultimate commercialization and use. The panel will also provide an in depth look at precision medicine approaches aimed at better understanding and improving patient care in highly complex disease areas like neurology.
Speaker panel:  The big issue now with precision medicine is there is so much data and hard to put experimental design and controls around randomly collected data.
  • The frontier is how to CURATE randomly collected data to make some sense of it
  • One speaker was at a cancer meeting and the oncologist had no idea what to make of genomic reports they were given.  Then there is a lack of action or worse a misdiagnosis.
  • So for e.g. with Artificial Intelligence algorithms to analyze image data you can see things you can’t see with naked eye but if data quality not good the algorithms are useless – if data not curated properly data is wasted
Data needs to be organized and curated. 
If relying of AI for big data analysis the big question still is: what are the rates of false negative and false positives?  Have to make sure so no misdiagnosis.

Please follow LIVE on TWITTER using the following @ handles and # hashtags:

@Handles

@pharma_BI

@AVIVA1950

@BIOConvention

# Hashtags

#BIO2019 (official meeting hashtag)

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Live Conference Coverage @MedCity news Converge 2018 Philadelphia: Early Diagnosis Through Predictive Biomarkers, NonInvasive Testing, 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)

5:00 – 5:45 PM Early Diagnosis Through Predictive Biomarkers, NonInvasive Testing

Reporter: Stephen J. Williams, Ph.D.

 

Diagnosing cancer early is often the difference between survival and death. Hear from experts regarding the new and emerging technologies that form the next generation of cancer diagnostics.

Moderator: Heather Rose, Director of Licensing, Thomas Jefferson University
Speakers:
Bonnie Anderson, Chairman and CEO, Veracyte @BonnieAndDx
Kevin Hrusovsky, Founder and Chairman, Powering Precision Health @KevinHrusovsky

Bonnie Anderson and Veracyte produces genomic tests for thyroid and other cancer diagnosis.  Kevin Hrusovksy and Precision Health uses peer reviewed evidence based medicine to affect precision medicine decision.

Bonnie: aim to get a truth of diagnosis.  Getting tumor tissue is paramount as well as properly preserved tissue.  They use deep RNA sequencing  and machine learning  in their clinically approved tests.

Kevin: Serial biospace entrepreneur.  Two diseases, cancer and neurologic, have been diseases which have been hardest to get reproducible and validated biomarkers of early disease.  He concentrates on protein biomarkers.

Heather:  FDA has recently approved drugs for early disease intervention.  However the use of biomarkers can go beyond patient stratification in clinical trials.

Kevin: 15 approved drugs for MS but the markers are scans looking for brain atrophy which is too late of an endpoint.  So we need biomarkers of early disease progression.  We can use those early biomarkers of disease progression so pharma can target those early biomarkers and or use those early biomarkers of disease progression  for endpoint

Bonnie: exciting time in the early diagnostics field. She prefers transcriptomics to DNA based methods such as WES or WGS (whole exome or whole genome sequencing).  It was critical to show data on the cost savings imparted by their transcriptomic based thryoid cancer diagnostic test for payers to consider this test eligible for reimbursement.

Kevin: There has been 20 million  CAT scans for  cancer but it is estimated 90% of these scans led to misdiagnosis. Biomarker  development  has revolutionized diagnostics in this disease area.  They have developed a breakthrough panel of ten protein biomarkers in serum which he estimates may replace 5 million mammograms.

All panelists agreed on the importance of regulatory compliance and the focus of new research should be on early detection.  In addition they believe that Dr. Gotlieb’s appointment to the FDA is a positive for the biomarker development field, as Dr. Gotlieb understands the potential and importance of early detection and prevention of disease.  Kevin also felt Dr. Gotlieb understands the importance of incorporating biomarkers as endpoints in clinical trials.  Over 750 phase 1,2, and 3 clinical trials use biomarker endpoints but the pharma companies still need to prove the biomarkers clinical relevance to the FDA.They also agreed it would be helpful to involve advocacy groups in putting more pressure on the healthcare providers and policy makers on this importance of diagnostics as a preventative measure.

In addition, the discovery and use of biomarkers as disease endpoints has led to a resurgence of Alzheimer’s disease drug development by companies which have previously given up on these type of neurodegenerative diseases.

Kevin feels proteomics offers great advantages over DNA-based diagnostics, especially in cancer such as ovarian cancer, where a high degree of specificity for a diagnostic test is required to ascertain if a woman should undergo prophylactic oophorectomy.  He suggests that a new blood-based protein biomarker panel is being developed for early detection of some forms of ovarian cancer.

Please follow on Twitter using the following #hash tags and @pharma_BI

#MCConverge

#cancertreatment

#healthIT

#innovation

#precisionmedicine

#healthcaremodels

#personalizedmedicine

#healthcaredata

And at the following handles:

@pharma_BI

@medcitynews

 

Please see related articles on Live Coverage of Previous Meetings on this Open Access Journal

LIVE – Real Time – 16th Annual Cancer Research Symposium, Koch Institute, Friday, June 16, 9AM – 5PM, Kresge Auditorium, MIT

Real Time Coverage and eProceedings of Presentations on 11/16 – 11/17, 2016, The 12th Annual Personalized Medicine Conference, HARVARD MEDICAL SCHOOL, Joseph B. Martin Conference Center, 77 Avenue Louis Pasteur, Boston

Tweets Impression Analytics, Re-Tweets, Tweets and Likes by @AVIVA1950 and @pharma_BI for 2018 BioIT, Boston, 5/15 – 5/17, 2018

BIO 2018! June 4-7, 2018 at Boston Convention & Exhibition Center

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

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Curator: Aviva Lev-Ari, PhD, RN

 

Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness

Published online: 26 July 2017

URMC Researchers Developing New Tool to Fight Antibiotic Resistance

Goal is to Distinguish Between Viral and Bacterial Infections, Reduce Unnecessary Use of Antibiotics

Friday, July 28, 2017

“It’s extremely difficult to interpret what’s causing a respiratory tract infection, especially in very ill patients who come to the hospital with a high fever, cough, shortness of breath and other concerning symptoms,” said Ann R. Falsey, M.D., lead study author, professor and interim chief of the Infectious Diseases Division at UR Medicine’s Strong Memorial Hospital.

“My goal is to develop a tool that physicians can use to rule out a bacterial infection with enough certainty that they are comfortable, and their patients are comfortable, foregoing an antibiotic.”

Lead researcher Ann Falsey, M.D.

Ann R. Falsey, M.D.

Falsey’s project caught the attention of the federal government; she’s one of 10 semifinalists in the Antimicrobial Resistance Diagnostic Challenge, a competition sponsored by NIH and the Biomedical Advanced Research and Development Authority to help combat the development and spread of drug resistant bacteria. Selected from among 74 submissions, Falsey received $50,000 to continue her research and develop a prototype diagnostic test, such as a blood test, using the genetic markers her team identified.

SOURCE

https://www.urmc.rochester.edu/news/story/5108/urmc-researchers-developing-new-tool-to-fight-antibiotic-resistance.aspx

Lower respiratory tract infection (LRTI)

We enrolled 94 subjects who were microbiologically classified; 53 as “non-bacterial” and 41 as “bacterial”. RNAseq and qPCR confirmed significant differences in mean expression for 10 genes previously identified as discriminatory for bacterial LRTI. A novel dimension reduction strategy selected three pathways (lymphocyte, α-linoleic acid metabolism, IGF regulation) including eleven genes as optimal markers for discriminating bacterial infection (naïve AUC = 0.94; nested CV-AUC = 0.86). Using these genes, we constructed a classifier for bacterial LRTI with 90% (79% CV) sensitivity and 83% (76% CV) specificity. This novel, pathway-based gene set displays promise as a method to distinguish bacterial from nonbacterial LRTI.

https://www.nature.com/articles/s41598-017-06738-3#Sec8

IMAGE SOURCE

https://www.nature.com/articles/s41598-017-06738-3#Sec8

 

SOURCES

http://sciencemission.com/site/index.php?page=news&type=view&id=microbiology-virology%2Fnew-tool-to-distinguish&filter=8%2C9%2C10%2C11%2C12%2C13%2C14%2C16%2C17%2C18%2C19%2C20%2C27&redirected=1&redirected=1

https://www.urmc.rochester.edu/news/story/5108/urmc-researchers-developing-new-tool-to-fight-antibiotic-resistance.aspx

https://www.nature.com/articles/s41598-017-06738-3

Bacterial or Viral Infection? A New Study May Help Physicians …

 

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

Series D, VOLUME 2:

Infectious Diseases and Therapeutics

Author, Curator and Editor: Larry H Bernstein, MD, FCAP and CuratorSudipta Saha, PhD

 

Series D, VOLUME 3:

The Immune System and Therapeutics

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

https://pharmaceuticalintelligence.com/biomed-e-books/series-d-e-books-on-biomedicine/human-immune-system-in-health-and-in-disease/

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