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2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021

 

The 2021 Virtual World Medical Innovation Forum will focus on the growing impact of gene and cell therapy.
Senior healthcare leaders from all over look to shape and debate the area of gene and cell therapy. Our shared belief: no matter the magnitude of change, responsible healthcare is centered on a shared commitment to collaborative innovation–industry, academia, and practitioners working together to improve patients’ lives.

https://worldmedicalinnovation.org/agenda/

Virtual | May 19–21, 2021

 

 

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

will cover the event in Real Time

 

Aviva Lev-Ari, PhD, RN

Founder LPBI 1.0 & LPBI 2.0

will be in attendance producing the e-Proceedings

and the Tweet Collection of this Global event expecting +15,000 attendees

 

 

LPBI’s Eighteen Books in Medicine

https://lnkd.in/ekWGNqA

Among them, books on Gene and Cell Therapy include the following:

 

 

Topics

The 2021 Forum will be held virtually and focus on gene and cell therapy.

AAV | Ophthalmology, Otology and Neurology

Gene Therapy | Oncolytic Viruses

CAR- T | Cellular Therapies

Stem Cells | Neurodegenerative Diseases, Regenerative Medicine

GCT | Infectious Disease, Hematology and Diabetes

Gene Editing | RNA Technologies

GCT Manufacturing | Supply Chain

Equity and Access | Emerging GCT Environment

GCT Investor Priorities

Putting GCT to Work | Payers, Providers | Regulatory

*Our agenda is currently under formation and is subject to change. Please continue checking for a more up to date agenda.


Inhibitory CD161 receptor recognized as a potential immunotherapy target in glioma-infiltrating T cells by single-cell analysis

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

 

Brain tumors, especially the diffused Gliomas are of the most devastating forms of cancer and have so-far been resistant to immunotherapy. It is comprehended that T cells can penetrate the glioma cells, but it still remains unknown why infiltrating cells miscarry to mount a resistant reaction or stop the tumor development.

Gliomas are brain tumors that begin from neuroglial begetter cells. The conventional therapeutic methods including, surgery, chemotherapy, and radiotherapy, have accomplished restricted changes inside glioma patients. Immunotherapy, a compliance in cancer treatment, has introduced a promising strategy with the capacity to penetrate the blood-brain barrier. This has been recognized since the spearheading revelation of lymphatics within the central nervous system. Glioma is not generally carcinogenic. As observed in a number of cases, the tumor cells viably reproduce and assault the adjoining tissues, by and large, gliomas are malignant in nature and tend to metastasize. There are four grades in glioma, and each grade has distinctive cell features and different treatment strategies. Glioblastoma is a grade IV glioma, which is the crucial aggravated form. This infers that all glioblastomas are gliomas, however, not all gliomas are glioblastomas.

Decades of investigations on infiltrating gliomas still take off vital questions with respect to the etiology, cellular lineage, and function of various cell types inside glial malignancies. In spite of the available treatment options such as surgical resection, radiotherapy, and chemotherapy, the average survival rate for high-grade glioma patients remains 1–3 years (1).

A recent in vitro study performed by the researchers of Dana-Farber Cancer Institute, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard, USA, has recognized that CD161 is identified as a potential new target for immunotherapy of malignant brain tumors. The scientific team depicted their work in the Cell Journal, in a paper entitled, “Inhibitory CD161 receptor recognized in glioma-infiltrating T cells by single-cell analysis.” on 15th February 2021.

To further expand their research and findings, Dr. Kai Wucherpfennig, MD, PhD, Chief of the Center for Cancer Immunotherapy, at Dana-Farber stated that their research is additionally important in a number of other major human cancer types such as 

  • melanoma,
  • lung,
  • colon, and
  • liver cancer.

Dr. Wucherpfennig has praised the other authors of the report Mario Suva, MD, PhD, of Massachusetts Common Clinic; Aviv Regev, PhD, of the Klarman Cell Observatory at Broad Institute of MIT and Harvard, and David Reardon, MD, clinical executive of the Center for Neuro-Oncology at Dana-Farber.

Hence, this new study elaborates the effectiveness of the potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several natural killer (NK) cell genes.

The Study-

IMAGE SOURCE: Experimental Strategy (Mathewson et al., 2021)

 

The group utilized single-cell RNA sequencing (RNA-seq) to mull over gene expression and the clonal picture of tumor-infiltrating T cells. It involved the participation of 31 patients suffering from diffused gliomas and glioblastoma. Their work illustrated that the ligand molecule CLEC2D activates CD161, which is an immune cell surface receptor that restrains the development of cancer combating activity of immune T cells and tumor cells in the brain. The study reveals that the activation of CD161 weakens the T cell response against tumor cells.

Based on the study, the facts suggest that the analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 that codes for CD161 as a candidate inhibitory receptor. This was followed by the use of 

  • CRISPR/Cas9 gene-editing technology to inactivate the KLRB1 gene in T cells and showed that CD161 inhibits the tumor cell-killing function of T cells. Accordingly,
  • genetic inactivation of KLRB1 or
  • antibody-mediated CD161 blockade

enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other forms of human cancers. The work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immune checkpoint targets.

Further, it has been identified that many cancer patients are being treated with immunotherapy drugs that disable their “immune checkpoints” and their molecular brakes are exploited by the cancer cells to suppress the body’s defensive response induced by T cells against tumors. Disabling these checkpoints lead the immune system to attack the cancer cells. One of the most frequently targeted checkpoints is PD-1. However, recent trials of drugs that target PD-1 in glioblastomas have failed to benefit the patients.

In the current study, the researchers found that fewer T cells from gliomas contained PD-1 than CD161. As a result, they said, “CD161 may represent an attractive target, as it is a cell surface molecule expressed by both CD8 and CD4 T cell subsets [the two types of T cells engaged in response against tumor cells] and a larger fraction of T cells express CD161 than the PD-1 protein.”

However, potential side effects of antibody-mediated blockade of the CLEC2D-CD161 pathway remain unknown and will need to be examined in a non-human primate model. The group hopes to use this finding in their future work by

utilizing their outline by expression of KLRB1 gene in tumor-infiltrating T cells in diffuse gliomas to make a remarkable contribution in therapeutics related to immunosuppression in brain tumors along with four other common human cancers ( Viz. melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma, and colorectal cancer) and how this may be manipulated for prevalent survival of the patients.

References

(1) Anders I. Persson, QiWen Fan, Joanna J. Phillips, William A. Weiss, 39 – Glioma, Editor(s): Sid Gilman, Neurobiology of Disease, Academic Press, 2007, Pages 433-444, ISBN 9780120885923, https://doi.org/10.1016/B978-012088592-3/50041-4.

Main Source

Mathewson ND, Ashenberg O, Tirosh I, Gritsch S, Perez EM, Marx S, et al. 2021. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. Cell.https://www.cell.com/cell/fulltext/S0092-8674(21)00065-9?elqTrackId=c3dd8ff1d51f4aea87edd0153b4f2dc7

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First single-course ‘curative’ CRISPR Shot by Intellia rivals Alnylam, Ionis and Pfizer

Reporter: Aviva Lev-Ari, PhD, RN

 

Intellia to kick-start first single-course ‘curative’ CRISPR shot, as it hopes to beat rivals Alnylam, Ionis and Pfizer

It’s been a good year for Intellia: One of its founders, Jennifer Doudna, Ph.D., nabbed the Nobel Prize in Chemistry for her CRISPR research.

Now, the biotech she helped build is putting that to work, saying it now plans the world’s first clinical trial for a single-course therapy that “potentially halts and reverses” a condition known as hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN).

This genetic disorder occurs when a person is born with a specific DNA mutation in the TTR gene, which causes the liver to produce a protein called transthyretin (TTR) in a misfolded form and build up in the body.

hATTR can manifest as polyneuropathy (hATTR-PN), which can lead to nerve damage, or cardiomyopathy (hATTR-CM), which involves heart muscle disease that can lead to heart failure.

This disorder has seen a lot of interest in recent years, with an RNAi approach from Alnylam seeing an approval for Onpattro a few years back, specifically for hATTR in adults with damage to peripheral nerves.

Ionis Pharmaceuticals and its rival RNAi drug Tegsedi also saw an approval in 2018 for a similar indication.

They both battle with Pfizer’s older med tafamidis, which has been approved in Europe for years in polyneuropathy, and the fight could spread to the U.S. soon.

The drug, now marketed as Vyndaqel and Vyndamax, snatched up an FDA nod last May to treat both hereditary and wild-type ATTR patients with a heart condition called cardiomyopathy.

While coming into an increasingly crowed R&D area, Intellia is looking for a next-gen approach, and has been given the go-ahead by regulators ion the U.K, to start a phase 1 this year.

The idea is for Intellia’s candidate NTLA-2001, which is also partnered with Regeneron, to go beyond its rivals and be the first curative treatment for ATTR.

By applying the company’s in vivo liver knockout technology, NTLA-2001 allows for the possibility of lifelong transthyretin (TTR) protein reduction after a single course of treatment. If this works, this could in essence cure patients of the their disease.

The 38-patient is set to start by year’s end.

“Starting our global NTLA-2001 Phase 1 trial for ATTR patients is a major milestone in Intellia’s mission to develop medicines to cure severe and life-threatening diseases,” said Intellia’s president and chief John Leonard, M.D.

“Our trial is the first step toward demonstrating that our therapeutic approach could have a permanent effect, potentially halting and reversing all forms of ATTR. Once we have established safety and the optimal dose, our goal is to expand this study and rapidly move to pivotal studies, in which we aim to enroll both polyneuropathy and cardiomyopathy patients.”

SOURCE

https://www.fiercebiotech.com/biotech/intellia-to-kickstart-first-single-course-curative-crispr-shot-as-it-hopes-to-beat-rivals

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Contribution of Nervous System Functional Deterioration to late-life Mortality: The Role Neurofilament light chain (NfL) a Blood Biomarker for the Progression of Neurological Diseases and its Correlation to Age and Life Expectancy

 

Reporter: Aviva Lev-Ati, PhD, RN

 

A neuronal blood marker is associated with mortality in old age

Abstract

Neurofilament light chain (NfL) has emerged as a promising blood biomarker for the progression of various neurological diseases. NfL is a structural protein of nerve cells, and elevated NfL levels in blood are thought to mirror damage to the nervous system. We find that plasma NfL levels increase in humans with age (n = 122; 21–107 years of age) and correlate with changes in other plasma proteins linked to neural pathways. In centenarians (n = 135), plasma NfL levels are associated with mortality equally or better than previously described multi-item scales of cognitive or physical functioning, and this observation was replicated in an independent cohort of nonagenarians (n = 180). Plasma NfL levels also increase in aging mice (n = 114; 2–30 months of age), and dietary restriction, a paradigm that extends lifespan in mice, attenuates the age-related increase in plasma NfL levels. These observations suggest a contribution of nervous system functional deterioration to late-life mortality.

SOURCE

How long will a healthy older person live? A substance in blood may provide a clue

Levels of a substance in nonagenerians’ and centenarians’ blood accurately predict how much longer they’re going to live. The substance comes from the brain.

The findings, in a study published in Nature Aging, could prove useful in developing life-extending drugs. They also raise questions about the brain’s role in aging and longevity.

The study, conducted by Stanford investigators including neuroscientist Tony Wyss-Coray, PhD, in collaboration with researchers in Denmark and Germany, zeroed in on a substance whose technical name is neurofilament light chain (abbreviated NfL). A structural protein produced in the brain, NfL is found in trace amounts in cerebrospinal fluids and blood, where it’s an indicator of damage to long extensions of nerve cells called axons.

Axons convey signals from one nerve cell to the next and are critical to all brain function. You’d rather they remain intact.

Too much NfL (different from the NFL)

High NfL levels in the blood have previously been associated with Alzheimer’s disease, multiple sclerosis, Huntington’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease) and other neurological disorders. But the people monitored in the new study were generally pretty healthy for their age.

The researchers first looked at 122 people whose ages ranged from 21 to 107, and found increasing blood levels of NfL — as well as increasing variation among individuals — with increasing age.

Next, the scientists followed the fates of 135 people age 100 or over for a four-year period. Most of those centenarians were in good shape to begin with, as shown by their performance on standard tests of mental ability and by a measure of their capacity to meet the routine demands of daily living.

Not unexpectedly, those whose mental tests indicated impairment had more NfL in their blood than those with the sharpest minds did. And those with low levels were substantially likelier to live longer than those with high levels.

A look at people in their 90s confirmed the findings in the over-100 group. Blood NfL levels among 180 93-year-olds not only predicted the duration of these folks’ survival, but did so better than mental or daily-coping test scores did.

The investigators showed that mice’s blood NfL levels, too, increase with age. But cutting their caloric intake, beginning in young adulthood — already known to prolong the lives of mice and numerous other species — chopped the little creatures’ blood levels of this substance in half in old age. (This new finding doesn’t prove that lowering NfL blood levels causes increased longevity, but it’s consistent with it.)

Tie to life expectancy?

At a minimum, NfL appears to accurately flag mortality’s approach. That means it might be possible to monitor it as a surrogate marker for remaining life expectancy, much as blood cholesterol levels are used as proxies for cardiovascular health. If so, it could someday help drug developers assess life-extending interventions’ efficacy.

Clinical trials of interventions believed to enhance longevity have been impractical, because it would almost certainly take so long to get a statistically significant result that such trials would be hugely expensive — a major hang-up for pharmas considering investment in longevity drugs. But monitoring a proxy such as NfL could cut years off of such trials’ duration, perhaps encouraging drug developers to dive into the clinical arena with life-prolonging pharmacological candidates.

Possibly most intriguing of all: The new findings hint that maintaining a healthy brain in old age is the best route to a long life.

“It will be interesting to see how and why the brain might be so important in counting down our final years and months,” Wyss-Coray told me.

Photo by Pablo Bendandi


COVID-19-vaccine rollout risks and challenges

Reporter : Irina Robu, PhD

BioNTech and Pfizer and Moderna COVID-19 vaccines received Emergency Use Authorization in January 2021 in Canada, European Union, United Kingdom and United States. However, in certain places COVID-19 has hit a few hindrances such as stockpiles have accumulated, deployment to vulnerable countries and at-risk groups has been slower than expected.  Yet, experts can see the light at the end of the tunnel of the pandemic. In United States, hundred of organization take a vital role in vaccine deployment, adapting their operations to meet the demands for volume, speed and better technology. Tens of thousands of transporters, vaccine handlers, medical and pharmacy staff, and frontline workers have mandatory training on the specific characteristics of each manufacturer’s distinct vaccines.

The common operating model provides the details of end-to-end vaccine deployment. Possible areas of risk to the rapid delivery of COVID-19 vaccines in the United States include:

Raw-materials constraints in production scaling

Scaling access to material and boosting production levels can cause logistical, contractual and even diplomatic challenges, requiring new forms of collaboration. The top two US manufacturers, for example, can produce 280 million vials per year, capable of holding up to 2.8 billion doses.

Quality-assurance challenges in manufacturing

Generating yields to produce a new class of vaccines—such as those based on mRNA or viral vectors—at an unprecedented scale (1.8 billion to 2.3 billion doses by mid-2021), manufacturers have required massive volumes of inputs, a larger technical workforce.

Cold-chain logistics and storage-management challenges

Manufacturers and distributors are preparing to maintain cold-chain requirements for distribution and long-term storage of mRNA-based vaccines. Large amounts of dry ice may be needed at various locations before administration.

Increased labor requirements

Complex protocols for handling and preparing COVID-19 vaccines have the potential to strain labor capacities or divert workers from other critical roles.

Wastage at points of care

Errors in storing, preparing, or scheduling administration of doses at points of care will have significant consequences and proper on-site storage conditions are also of critical importance.

IT challenges

IT systems, including vaccine-tracking systems and immunization information systems will be vital for allocating, distributing, recording, and monitoring the deployment of vaccines.

There are several possible approaches to help mitigate each of the six risks discussed, each with practical steps for organization to take across the common operating model.

Building resilient raw-materials supplies

  • Resilience planning.Producers can partner with global suppliers of raw materials and ancillary-product manufacturers to create redundancies.
  • Collaboration between industry and government.Ongoing industry engagement with government is essential for ramping-up production and maintaining high levels of production.

 Scaling manufacturing within quality guidelines

  • Scale manufacturing in new and existing facilities.  Various digital and analytics tools can help expand capacity and scale more quickly.
  • Assure quality and yield in current facilities. By continuing to coordinate with regulators, manufacturers and authorities can certify that procedures and dosage quality meet both long-established and newly issued guidelines.
  • Establish predictable supplier plans. Each manufacturing stakeholder can follow a clearly defined plan and they can also conduct regular cross-functional risk reviews to ensure that quality.

Optimizing the cold chain

  • Build redundancy into distribution.Manufacturers, distributers should quickly identify points of failure and creating redundancies at each stage.
  • Leverage feedback loops.Reporting systems could be set up to capture supply-chain disruption events as soon as they happen, with data used to refine best practices and procedures and avoid further losses.
  • Use point-of-care stock management.Vaccine inventories can be redistributed to locations with greater demand. Strategies to avoid over stockpiling must confirm maintenance of the cold chain to prevent risks to the receiving administration site.

Addressing labor shortages

  • Use several types of point-of-care facilities.Rely on hospitals and primary-care locations for vaccine administration, in addition to retail pharmacies.
  • Streamline administration across sites.Deploying vaccines at larger, streamlined vaccination sites can be more efficient and improve patient safety, labor utilization, and speed of vaccination.

 Reducing spoilage at points of care

  • Track and monitor spoilage at points of care.Manufacturers and distributors can collaborate to establish the means to identify and trace instances of spoilage. They can learn from experience and refine guidance, training, certification, and allocation to optimize utilization of doses.
  • Pace first-dose allocation.Allocation of first doses to populations and locations where the need is greatest and the confidence in the availability of second doses is high (such as healthcare professionals and vulnerable populations in nursing homes).
  • Prioritize second doses.Authorities can help ensure that the recommended two-dose course schedule for such vaccines as the Pfizer-BioNTech, Moderna, and AstraZeneca vaccines are duly completed.
  • Establish recipient commitment.Vaccine recipients could be asked to commit to second-dose appointments at their point of care before first-dose administration.
  • Manage certification.National and local government institutions can collaborate to ensure that vaccination certifications are withheld until recipients receive their second dose.

Meeting IT challenges

  • Balance IT upgrades and resilience.Stakeholders should identify IT systems that can be relied upon in the deployment of COVID-19 vaccines and assess their ability to perform at scale.
  • Share cyberthreat intelligence.COVID-19-vaccine stakeholders should agree upon common requirements and processes for generating and sharing threat intelligence.
  • Establish means of demonstrating immunity.Manufacturers and distributers can commission systems to track and verify that vaccine recipients have demonstrated immunity. if it will release them from travel limits and other pandemic-related restrictions.

Although not one organization is involved for managing vaccine deployment, but the risks can be fully address if organizations align on lead organization to build scenarios to test responses to emerging crises. The groups could align on lead organizations to manage issues while building scenarios to test responses to emerging crises. The benefits in managing each of these risks could be demonstrated with compelling metrics and communications.  As COVID-19-vaccine rollouts commence, the steps mentioned above can be undertaken by manufactures, distributors and governments.

SOURCE

https://www.mckinsey.com/business-functions/risk/our-insights/the-risks-and-challenges-of-the-global-covid-19-vaccine-rollout?cid=other-eml-nsl-mip-mck&hlkid=19a51f848bee4d00806d2da81315f70d&hctky=2071733&hdpid=062f1841-f911-48f3-ab14-a9f92e30721f#


Glycosylation and its Role in SARS-CoV-2 Viral Pathogenesis

Author: Meg Baker, PhD

 

N-Glycosylation and COVID19

Glycobiology

N-linked glycosylation (NLG) is a complex biosynthetic process that regulates proper folding of proteins through and intracellular transport of proteins to the secretory pathway. This co- and post-translational modification occurs by a series of enzymatic reactions, which results in the transfer of a core glycan from the lipid carrier to a protein substrate and the possibility for further remodeling of the glycan. The enzymes are located in the cytosolic and the luminal side of the ER membrane. The study of NLG and related effects of glycans is called glycobiology.

NLG takes place at sites specified in the protein sequence itself. N-linked oligosaccharides are attached via a GlcNAc linked to the side chain nitrogen of Asn found in the consensus sequence NXT/S (X ≠ P) known as the ‘glycosylation sequon’. Formation of a precursor branched carbohydrate chain, the lipid-linked oligosaccharide (LLO) structure, takes place in the endoplasmic reticulum. The LLO consists of a Glc3Man9GlcNAc2 molecule (three glucose, nine mannose, and two N-acetylglucosamine sugars) linked to a dolichol pyrophosphate. The enzyme oligosaccharyltransferase then moves it to an Asn in the polypeptide.

The removal of the three glucose sugars from the new N-linked glycan signals that the structure is ready for transport to the Golgi where mannose is removed yielding a carbohydrate chain containing five–nine mannose sugars. Further removal of mannose residues can lead to the core structure containing three mannose and two N-acetylglucosamine residues, which may then be elongated with a variety of different monosaccharides including galactose, N-acetylglucosamine (aka NAG or GlcNac), N-acetylgalactosamine, fucose, and sialic acid, many of which can also exist in sulfated form.

The enzymes involved in this essential process are evolutionarily conserved. However, the genes and their specific functions, have evolved uniquely for each selected organism. Therefore, each organism and each individual cell, depending on genetic background and influenced by nutritional and such things as disease status, will decorate secreted proteins in a unique manner.

The advent of biologic medicines (protein based therapeutics) presents the challenge of making sure that the primary protein sequence is specified but also that the manufacture of the protein – typically in a eukaryotic cell host capable of glycosylation – will take place with some degree of reproducibility. The large number of monoclonal antibody therapeutics absolutely require glycosylation for proper structural integrity but are generally made in rodent or other nonhuman cells. Thus, the term “biosimilar” rather than generic is the term being used to connote the variation which will necessarily result due to different manufacturing process even of the same genetic sequence.

 

Viral Glycoproteins

It should be obvious that the viral genome is not large enough to encompass the collection of enzymes required for glycosylation of any type and viral glycoproteins are formed by the host cell in which the virus is replicating. The study of the impact of glycan content and composition on viral infectivity and, more importantly, vaccine development is a subject which has been late to be addressed largely due to the technical difficulty and lack of methods for analyzing protein glycan composition. However, progress is being made. Raska et al. (J Biol Chem 2010 Jul 2; 285(27): 20860–20869. Glycosylation Patterns of HIV-1 gp120 Depend on the Type of Expressing Cells and Affect Antibody Recognition)  was able to perform such an analysis on the HIV-1 virus albeit almost 30 years after its emergence in human populations. The findings of this study may explain, in part, the difficulty in developing a vaccine against HIV.

 

SARS-CoV-2 spike protein (P0DTC2 uniprot.org) – as so popularly depicted – is a trimer poking out of the lipid coat that protects it’s genome. The spike protein, like gp120 in HIV, is the point of contact with the human cell ACE2 receptor it uses to gain entry. The spike protein contains two functional external subunits, designated S1 and S2. S1 separated by a furin cleavage site from S2, forms the apex of the trimeric spike structure, is responsible for attachment to the ACE2 receptor. S2 is responsible for fusion to the cell membrane. (PDB: 6VSB shows a 3D image of the protein structure, including glycan positions). There are 22 glycans per polypeptide or 66 per spike trimer protein (Watanabe et al. 2021 Site-specific glycan analysis of the SARS-CoV-2 spike. Science 17 Jul 2020:Vol. 369, Issue 6501, pp. 330-333 ).

Although shielding of receptor binding sites by glycans is a common feature of viral glycoproteins, Watanabe (ibid) note the low mutation rate of SARS-CoV-2 and that as yet, there have been no observed mutations to N-linked glycosylation sites.

The development of a vaccine or individual antibodies or antibody cocktails with neutralizing (viral entry blocking or virocidal activity) is also influenced by the presence or absence of glycans and how well they target the natural conformation of the spike protein. Papageorgiou et al. The SARS-CoV-2 Spike Glycoprotein as a Drug and Vaccine Target: Structural Insights into Its Complexes with ACE2 and Antibodies. Cells 2020 Oct 22;9(11):2343. doi: 10.3390/cells9112343. SARS-CoV-2 Spike – Stanford Coronavirus Antiviral Research Database It should be noted that the mRNA vaccines (or other nucleic acid formats) may obviate these analysis because the immune response is to a spike protein made and glycosylated in the human host’s own body and therefore will be customized to each individual in some sense.

Glycans may themselves represent drug targets. Casolino et al. suggest an essential structural role of N-glycans at sites N165 and N234 in modulating the conformational dynamics of the spike’s receptor binding domain (RBD), which is responsible for ACE2 recognition (Casolino et al. 2020. Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein ACS Cent Sci. 2020 Oct 28; 6(10): 1722–1734),

 

COVID19 Variants

SARS-CoV-2 lineage B.1.1.7 likely arose in the United Kingdom in September 2019 and is characterized by 17 mutations, including 8 in the spike protein (Rambaut et al., 2020). Other lineages, including B.1.351, initially detected in South Africa (Tegally et al., 2020), and most recently lineage P.1, first documented in the Amazonia region of Brazil (Faria et al., 2020), carry additional mutations. All three lineages are characterised by a N501Y (Asn to Tyr) mutation in the spike protein, while both B.1.351 and P.1 also carry the spike mutation E484K. In addition, both B.1.1.7 and B.1.351, but not P.1, have acquired short sequence deletions in the spike protein. N501Y is in the receptor-binding domain (RBD) but is not a glycosylation site.

Reference

See the CDC Emerging SARS-CoV-2 Variants | CDC

 


NLP Techniques based on NLP Year in Review — 2019 

Reporter: Aviva Lev-Ari, PhD, RN

 

Tags: 

In this blog post, I want to highlight some of the most important stories related to machine learning and NLP that I came across in 2019.


SAS AI/ML Training

By Elvis Saravia, Affective Computing & NLP Researcher

Other Related Topics

Activation Atlases is a technique developed by researchers at Google and Open AI to better understand and visualize the interactions happening between neurons of a neural network.

Figure

“An activation atlas of the InceptionV1 vision classification network reveals many fully realized features, such as electronics, buildings, food, animal ears, plants, and watery backgrounds.” — source

 

 

This Colab notebook provides a great introduction on how to use Nucleus and TensorFlow for “DNA Sequencing Error Correction”. And here is a great detailed post on the use of deep learning architectures for exploring DNA.

Figure

 

 

Alexander Rush is a Harvard NLP researcher who wrote an important article about the issues with tensors and how some current libraries expose them. He also went on to talk about a proposal for tensors with named indices.

 

ML/NLP Tools and Datasets ⚙️

 

StanfordNLP released StanfordNLP 0.2.0 which is a Python library for natural language analysis. You can perform different types of linguistic analysis such as lemmatization and part of speech recognition on over 70 different languages.

GQA is a visual question answering dataset for enabling research related to visual reasoning.

exBERT is a visual interactive tool to explore the embeddings and attention of Transformer language models. You can find the paper here and the demo here.

SOURCE

https://www.kdnuggets.com/2020/01/nlp-year-review-2019.html

 

 

6 NLP Techniques Every Data Scientist Should Know

Towards more efficient natural language processing

Sara A. Metwalli

Sara A. Metwalli

Ph.D. student working on Quantum Computing. Traveler, writing lover, science enthusiast, and CS instructor. Get in touch with me bit.ly/2CvFAw6

Jan 20·7 min read

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Photo by Sai Kiran Anagani on Unsplash

Natural language processing is perhaps the most talked-about subfield of data science. It’s interesting, it’s promising, and it can transform the way we see technology today. Not just technology, but it can also transform the way we perceive human languages.

Natural language processing has been gaining too much attention and traction from both research and industry because it is a combination between human languages and technology. Ever since computers were first created, people have dreamt about creating computer programs that can comprehend human languages.

The advances in machine learning and artificial intelligence fields have driven the appearance and continuous interest in natural language processing. This interest will only grow bigger, especially now that we can see how natural language processing could make our lives easier. This is prominent by technologies such as Alexa, Siri, and automatic translators.

The truth is, natural language processing is the reason I got into data science. I was always fascinated by languages and how they evolve based on human experience and time. I wanted to know how we can teach computers to comprehend our languages, not just that, but how can we make them capable of using them to communicate and understand us.

In this article, I will go through the 6 fundamental techniques of natural language processing that you should know if you are serious about getting into the field.

NLP 101: What is Natural Language Processing?

How did NLP start?

towardsdatascience.com

Lemmatization and stemming

Stemming and lemmatization are probably the first two steps to build an NLP project — you often use one of the two. They represent the field’s core concepts and are often the first techniques you will implement on your journey to be an NLP master.

Often, beginners tend to confuse the two techniques. Although they have their similarities, they are quite different.

  • Stemming: Stemming is a collection of algorithms that work by clipping off the end of the beginning of the word to reach its infinitive form.These algorithms do that by considering the common prefixes and suffixes of the language being analyzed. Clipping off the words can lead to the correct infinitive form, but that’s not always the case. There are many algorithms to perform stemming; the most common one used in English is the Porter stemmer. This algorithm contains 5 phases that work sequentially to obtain the word’s root.
  • Lemmatization: To overcome the flaws of stemming, lemmatization algorithms were designed. In these types of algorithms, some linguistic and grammar knowledge needs to be fed to the algorithm to make better decisions when extracting a word’s infinitive form. For lemmatization algorithms to perform accurately, they need to extract the correct lemma of each word. So, they often require a dictionary of the language to be able to categorize each word correctly.

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Image by the author, made using Canva

Based on these definitions, you can imagine that building a lemmatizer is more complex and more time consuming than building a stemmer. However, it is more accurate and will cause less noise in the final analysis results.

Keywords extraction

Keyword extraction — sometimes called keyword detection or keyword analysis — is an NLP technique used for text analysis. This technique’s main purpose is to automatically extract the most frequent words and expressions from the body of a text. It is often used as a first step to summarize the main ideas of a text and to deliver the key ideas presented in the text.

In the backend of keyword extraction algorithms lays the power of machine learning and artificial intelligence. They are used to extract and simplify a given text for it to be understandable by the computer. The algorithm can be adapted and applied to any type of context, from academic text to colloquial text used in social media posts.

Keywords extraction has many applications in today’s world, including social media monitoring, customer service/ feedback, product analysis, and search engine optimization.

Named Entity Recognition (NER)

Like stemming and lemmatization, named entity recognition, or NER, NLP’s basic and core techniques are. NER is a technique used to extract entities from a body of a text used to identify basic concepts within the text, such as people’s names, places, dates, etc.

NER algorithm has mainly two steps. First, it needs to detect an entity in the text and then categorize it into one set category. The performance of NER depends heavily on the training data used to develop the model. The more relevant the training data to the actual data, the more accurate the results will be.

another factor contributing to the accuracy of a NER model is the linguistic knowledge used when building the model. That being said, there are open NER platforms that are pre-trained and ready to use.

NER can be used in a varsity of fields, such as building recommendation systems, in health care to provide better service for patients, and in academia to help students get relevant materials to their study scopes.

Topic Modelling

You can use keyword extractions techniques to narrow down a large body of text to a handful of main keywords and ideas. From which, you can probably extract the main topic of the text.

Another, more advanced technique to identify a text’s topic is topic modeling—top modeling built upon unsupervised machine learning that doesn’t require a labeled data for training.

Multiple algorithms can be used to model a topic of text, such as Correlated Topic Model, Latent Dirichlet Allocation, and Latent Sentiment Analysis. The most commonly used approach is the Latent Dirichlet. This approach analyzes the text, breaks it down into words and statements, and then extracts different topics from these words and statements. All you need to do is feed the algorithm a body of text, and it will take it from there.

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Image by the author, made using Canva

Summarization

One of the useful and promising applications of NLP is text summarization. That is reducing a large body of text into a smaller chuck containing the text’s main message. This technique is often used in long news articles and to summarize research papers.

Text summarization is an advanced technique that used other techniques that we just mentioned to establish its goals, such as topic modeling and keyword extraction. The way this is established is via two steps, extract and then abstract.

In the extract phase, the algorithms create a summary by extracting the text’s important parts based on their frequency. After that, the algorithm generates another summary, this time by creating a whole new text that conveys the same message as the original text. There are many text summarization algorithms, e.g., LexRank and TextRank.

In LexRank, the algorithm categorizes the sentences in the text using a ranking model. The ranks are based on the similarity between the sentences; the more similar a sentence is to the rest of the text, the higher it will be ranked.

Sentiment Analysis

The most famous, well-known, and used NLP technique is, without a doubt, sentiment analysis. This technique’s core function is to extract the sentiment behind a body of text by analyzing the containing words.

The technique’s most simple results lay on a scale with 3 areas, negative, positive, and neutral. The algorithm can be more complex and advanced; however, the results will be numeric in this case. If the result is a negative number, then the sentiment behind the text has a negative tone to it, and if it is positive, then some positivity in the text.

Sentiment analysis is one of the broad applications of machine learning techniques. It can be implemented using either supervised or unsupervised techniques. Perhaps the most common supervised technique to perform sentiment analysis is using the Naive Bayes algorithm. Other supervised ML algorithms that can be used are gradient boosting and random forest.

NLP 101: Towards Natural Language Processing

10 steps to build a strong NLP foundation

Takeaways

Humans’ desire for computers to understand and communicate with them using spoken languages is an idea that is as old as computers themselves. Thanks to the rapid advances in technology and machine learning algorithms, this idea is no more just an idea. It is a reality that we can see and experience in our daily lives. This idea is the core diving power of natural language processing.

Natural language processing is one of today’s hot-topics and talent-attracting field. Companies and research institutes are in a race to create computer programs that fully understand and use human languages. Virtual agents and translators did improve rapidly since they first appeared in the 1960s.

Despite the different tasks that natural language processing can execute, to get in the field and start building your own projects, you need to be completely comfortable with the core 6 fundamental natural language processing techniques.

These techniques are the basic building blocks of most — if not all — natural language processing algorithms. So, if you understand these techniques and when to use them, nothing can stop you.

A Learning Path To Becoming a Data Scientist

The 10 steps roadmap to kickstarting your data science future


Podcast Episodes by THE EUROPEAN VC

Reporter: Aviva Lev-Ari, PhD, RN

 

Audio files are st:

The European VC

 

EPISODE #5: WILLIAM MCQUILLAN, FOUNDING PARTNER OF A VENTURE FIRM FOR GLOBALLY AMBITIOUS B2B COMPANIES

William is a founding partner of Frontline Ventures. Prior to starting Frontline, he was a founding employee at Ondra, an award-winning investment boutique that went from a 4 person team to 70+ employees in only 18 months. When Frontline was founded, William was 27 years old, making him the youngest VC ever to have raised a fund at that time (2012). Shortly after recording this episode William announced Frontline Fund III.

 

In this episode you will learn:

– How William has built a truly differentiated investment thesis for Frontline’s two funds.

– What William looks for in seed stage startups and why he believes integrity is all important and money cannot be the founder’s main driver.

– How William perceives the effects of Brexit and its implications for their investment strategy and work with startups.

– Why William is a supporter of founders taking a small bit of secondaries.

EPISODE #4: SHOMIT GHOSE, GP OF A SILICON VALLEY FIRM WITH 7 FUNDS UNDER ITS BELT

This episode runs contrary to what the European VC stands for and features an American VC from the Valley. However, the focus is on looking from the outside in, as well as carving out lessons learned from decades of collaboration across the Atlantic. Shomit Ghose is a General Partner of ONSET Ventures, a leading early stage venture firm operating out of Sand Hill Road, in Silicon Valley. With more than 130 startups and 7 funds under its belt, ONSET Ventures is a highly respected firm in the Valley. Shomit is a seasoned VC with multiple IPOs under his belt – both as an investor and as an entrepreneur.

 

In this episode you will learn:

– How the European and American VC landscapes differ and what we can learn from both.

– How to increase your presence and establish collaborations between US and European VCs.

– How to approach building a country-agnostic fund and the role of VCs, LPs and Institutions.

EPISODE #3 MICHAEL HANSEN, CEO OF A LEADING BUSINESS ANGEL ASSOCIATION IN EUROPE

Michael Hansen is the CEO of DanBAN, Denmark’s leading Business Angel Association. DanBAN consist of more than 200 active Angels who collectively invest in more than 30 M€ on an annual basis. Prior to joining DanBAN, Michael was the chief architect behind the sprawling investment environment around the Danish Robotics Cluster which is broadly recognized as one of the very strongest clusters for Robotics companies in Europe, if not the world.

In this episode, you will learn from a true investment cluster builder

– The importance of politicians making brave strategic decisions in promoting cluster development.

– The story of the Danish Robotics Cluster in which the first collaborative robots were hatched, counting with two acquisitions at a valuation of almost 1 billion EUR.

– How to work with national clusters to generate deal flow and fast track deals.

– Collaboration models between Business Angels and VCs.

EPISODE #2 STEPHAN MORAIS, FOUNDER AND MANAGING PARTNER OF A LEADING EARLY-STAGE DEEP TECH VC FIRM

Stephan Morais is the founder and Managing Partner of Indico Capital Partners, a leading early-stage deep tech VC firm. With a diversified background as an investment banker, consultant, entrepreneur and CEO, he has lived in 8 countries and 4 continents over the last 24 years, and acted as and advisor to politicians and European institutions. Prior to founding Indico, Stephan was an Executive Board Member at Caixa Capital, where he led investment rounds of many Portuguese global tech success stories.

In this episode, you’ll learn

– How Stephan tackled raising a VC fund and what to should look for in LPs

– How European VCs can push for policy developments that allow for more capital to be deployed into the industry

– What Europe can learn from other countries and regions

– What learnings Stephan has drawn from running an iberian fund

EPISODE #1 MARC LOHRMANN, MANAGING PARTNER OF A 120 M€ LIFE SCIENCE FUND

Marc Lohrmann is the Managing Partner of Vesalius Biocapital III, a 120 €M venture capital fund investing in late-stage companies in drug development, medical devices, diagnostics and eHealth, across Europe. Prior to joining Vesalius, Marc started eight life sciences companies, worked as an investment manager at a leading corporate VC and worked with several corporate finance boutiques focused on life sciences M&A transactions.

In this episode, you’ll learn

– How VBC III works as a country-agnostic VC fund and the main barriers to more funds investing across Europe.

– How investors without a natural sciences background can create value for Life Sciences companies and why founders find these investors a refreshing element in the board room.

– What Marc would love to change about European VC, what’s important when investing across Europe and what’s next for Marc.

 

 

 

 

SOURCE

https://www.theeuropeanvc.com/?utm_source=Sutardja%20Center%20Contacts&utm_campaign=f20d2f4f55-EMAIL_CAMPAIGN_2019_08_21_04_25_COPY_01&utm_medium=email&utm_term=0_8ae9d85a8f-f20d2f4f55-164676973


Need for Global Response to SARS-CoV-2 Viral Variants

Reporter: Aviva Lev-Ari, PhD, RN

NIH experts discuss SARS-CoV-2 viral variants

Editorial emphasizes need for global response.

 

The rise of several significant variants of SARS-CoV-2, the virus that causes COVID-19, has attracted the attention of health and science experts worldwide. In an editorial published today in JAMA: The Journal of the American Medical Association, experts from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, outline how these variants have arisen, concerns about whether vaccines currently authorized for use will continue to protect against new variants, and the need for a global approach to fighting SARS-CoV-2 as it spreads and acquires additional mutations.

The article was written by NIAID Director Anthony S. Fauci, M.D.; John R. Mascola, M.D., director of NIAID’s Vaccine Research Center (VRC); and Barney S. Graham, M.D., Ph.D., deputy director of NIAID’s VRC.

The authors note that the overlapping discovery of several SARS-CoV-2 variants has led to confusing terms used to name them. The appearance of SARS-CoV-2 variants is so recent that the World Health Organization and other groups are still developing appropriate nomenclature for the different variants.

Numerous SARS-CoV-2 variants have emerged over the last several months. The authors note that the variants known as B.1.1.7 (first identified in the United Kingdom) and B.1.351 (first identified in South Africa) concern scientists because of emerging data suggesting their increased transmissibility.

Variants can carry several different mutations, but changes in the spike protein of the virus, used to enter cells and infect them, are especially concerning. Changes to this protein may cause a vaccine to be less effective against a particular variant. The authors note that the B.1.351 variant may be partially or fully resistant to certain SARS-CoV-2 monoclonal antibodies currently authorized for use as therapeutics in the United States.

The recognition of all new variants, including a novel emergent strain (20C/S:452R) in California, requires systematic evaluation, according to the authors. The rise of these variants is a reminder that as long as SARS-CoV-2 continues to spread, it has the potential to evolve into new variants, the authors stress. Therefore, the fight against SARS-CoV-2 and COVID-19 will require robust surveillance, tracking, and vaccine deployment worldwide.

The authors also note the need for a pan-coronavirus vaccine. Once researchers know more about how the virus changes as it spreads, it may be possible to develop a vaccine that protects against most or all variants. While similar research programs are already in place for other diseases, such as influenza, the changing nature of SARS-CoV-2 indicates that they will be necessary for this virus.

SOURCE

https://www.nih.gov/news-events/news-releases/nih-experts-discuss-sars-cov-2-viral-variants

 

Editorial
February 11, 2021

SARS-CoV-2 Viral Variants—Tackling a Moving Target

JAMAPublished online February 11, 2021. doi:10.1001/jama.2021.2088

In this issue of JAMA, Zhang and colleagues1 report the emergence of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant in Southern California that accounted for 44% (37 of 85) of samples collected and studied in January 2021. The terminology of viral variation can be confusing because the media and even scientific communications often use the terms variantstrain, and lineage interchangeably. The terminology reflects the basic replication biology of RNA viruses that results in the introduction of mutations throughout the viral genome. When specific mutations, or sets of mutations, are selected through numerous rounds of viral replication, a new variant can emerge. If the sequence variation produces a virus with distinctly different phenotypic characteristics, the variant is co-termed a strain. When through genetic sequencing and phylogenetic analysis a new variant is detected as a distinct branch on a phylogenetic tree, a new lineage is born.

New variants become predominant through a process of evolutionary selection that is not well understood. Once identified, several questions arise regarding the potential clinical consequences of a new variant: Is it more readily transmitted; is it more virulent or pathogenic; and can it evade immunity induced by vaccination or prior infection? For these reasons, new viral variants are studied, leading to the terms variant under investigation or variant of concern.

To communicate effectively about new SARS-CoV-2 variants, a common nomenclature is needed, which like the virus, is evolving. Fortunately, the World Health Organization (WHO) is working on a systematic nomenclature that does not require a geographic reference, since viral variants can spread rapidly and globally. Currently, the terminology is overlapping, as reflected in the report by Zhang et al.1 This new variant (CAL.20C) is termed lineage 20C/S:452R in Nextstrain nomenclature,2 referring to the parent clade 20C and spike alteration 452R. Similarly, using a distinct PANGO nomenclature,3 this variant derives from lineage B (B.1.429 and B.1.427). While alterations in any viral genes can have implications for pathogenesis, those arising in the spike protein that mediates viral entry into host cells and is a key target of vaccines and monoclonal antibodies are of particular interest. The new variant, identified in California and termed 20C/S:452R, has 3 amino acid changes in the spike protein, represented using the single-letter amino acid nomenclature: S13I, W152C, and L452R. To interpret this new set of alterations, it is useful to review what is known about recent variants that have become predominant in other regions of the world.

During the early phase of the SARS-CoV-2 pandemic, there were only modest levels of genetic evolution; however, more recent information indicates that even a single amino acid substitution can have biological implications. Starting in April 2020, the original SARS-CoV-2 strain was replaced in many regions of the world by a variant called D614G, which was subsequently shown to increase the efficiency of viral replication in humans and was more transmissible in animal models.46 The D614G strain appears to position its receptor binding domain to interact more efficiently with the ACE2 receptor, and it is associated with higher nasopharyngeal viral RNA loads, which may explain its rise to dominance.

In October 2020, sequencing analysis in the UK detected an emerging variant, later termed B.1.1.7 or 20I/501Y.V1, which is now present and rapidly spreading in many countries.7 B.1.1.7 contains 8 mutations in the spike protein and maintains the D614G mutation. One of these, N501Y, appears to further increase the spike protein interaction with the ACE2 receptor. Epidemiological studies indicate that the B.1.1.7/20I/501Y.V1 strain is 30% to 80% more effectively transmitted and results in higher nasopharyngeal viral loads than the wild-type strain of SARS-CoV. Also of concern are retrospective observational studies suggesting an approximately 30% increased risk of death associated with this variant.8

Another notable variant, 20H/501Y.V2 or B.1.351, was first identified is South Africa, where it has rapidly become the predominant strain.9 Cases attributed to this strain have been detected in multiple countries outside of South Africa, including recent cases in the US. B.1.351 shares the D614G and N501Y mutations with B.1.1.1.7; thus, it is thought to also have a high potential for transmission. There are no data yet to suggest an increased risk of death due to this variant. Importantly, this constellation of mutations—9 total in the spike protein—add yet another dimension of concern. B.1.351 strains are less effectively neutralized by convalescent plasma from patients with coronavirus disease 2019 (COVID-19) and by sera from those vaccinated with several vaccines in development.1012 The decrement in neutralization can be more than 10-fold with convalescent plasma and averages 5- to 6-fold less with sera from vaccinated individuals. Fortunately, neutralization titers induced by vaccination are high, and even with a 6-fold decrease, serum can still effectively neutralize the virus.

Nonetheless, these data are concerning because they indicate that viral variation can result in antigenic changes that alter antibody-mediated immunity. This is highlighted by in vitro studies showing the B.1.351 strain to be partially or fully resistant to neutralization by certain monoclonal antibodies, including some authorized for therapeutic use in the US.12 The prevalent strains in the US appear to remain sensitive to therapeutic monoclonal antibodies; however, recent evolutionary history raises the concern that the virus could be only a few mutations away from more substantive resistance.

COVID-19 vaccine development has been an extraordinary success; however, it is unclear how effective these vaccines will be against the new variants. The interim data from 2 randomized placebo-controlled vaccine studies, the rAd26 from Janssen and a recombinant protein from Novavax, offer some insight. The Janssen study included sites in the US, Brazil, and South Africa with efficacy against COVID-19 at 72%, 66%, and 57%, respectively.13 Novavax reported efficacy from studies in the UK and South Africa with overall efficacy of 89% and 60%, respectively.14 Viral sequence data from infected patients showed that the B.1.351 strain was responsible for the majority of infections in South Africa. Lower vaccine efficacy in the South Africa cohort could be related to antigenic variation or to geographic or population differences. Despite the reduced efficacy, the rAd26 vaccine was 85% effective overall in preventing severe COVID-19, and protection was similar in all regions.

These data suggest that current vaccines could retain the ability to prevent hospitalizations and deaths, even in the face of decreased overall efficacy due to antigenic variation. It is unclear whether changes in vaccine composition will be needed to effectively control the COVID-19 pandemic; however, it is prudent to be prepared. Some companies have indicated plans to manufacture and test vaccines based on emerging variants, and such studies will provide important information on the potential to broaden the immune response.

The recognition of a novel emergent variant, 20C/S:452R, in the most populous US state necessitates further investigation for implications of enhanced transmission. In particular, the L452R mutation in the spike protein could affect the binding of certain therapeutic monoclonal antibodies. The emergence of this and other new variants is likely to be a common occurrence until the spread of this virus is reduced. This emphasizes the importance of a global approach to surveillance, tracking, and vaccine deployment. The approach should be systematic and include in vitro assessment of sensitivity to neutralization by monoclonal antibodies and vaccinee sera, vaccine protection of animals against challenge with new strains, and field data defining viral sequences from breakthrough infections in vaccinees. The infrastructure and process used for tracking and updating influenza vaccines could be used to inform that process. Finally, SARS-CoV-2 will be with the global population for some time and has clearly shown its tendency toward rapid antigenic variation, providing a “wake-up call” that a sustained effort to develop a pan-SARS-CoV-2 vaccine is warranted.

SOURCE

https://jamanetwork.com/journals/jama/fullarticle/2776542

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

Rise of a trio of mutated viruses hints at an increase in transmissibility, speeding the virus’ leaps from one host to the next

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/02/01/rise-of-a-trio-of-mutated-viruses-hints-at-an-increase-in-transmissibility-speeding-the-virus-leaps-from-one-host-to-the-next/

 


New approaches to cancer therapy using mathematics

Reporter: Irina Robu, PhD

Our bodies are made up of trillions of cells grouped together to form tissues and organs such as muscles, bones, the lungs and the liver. Genes inside each cell tell it when to grow, work, divide and die. Usually, our cells follow these commands and we stay healthy. Nevertheless, occasionally the instructions get mixed up, triggers our cells to grow and divide out of control or not die when they should. As more and more of these abnormal cells grow and divide, they can form a lump in the body called a tumor.

Cancer therapy thrives in shrinking tumors and frequently fails in the long run; however, a small number of cancer cells are resistant to treatment. The cancer cells expand to fill the space left by the cells that were destroyed.  Using mathematical analysis and numerical simulations, Dr. Noble and Dr. Viossat, a mathematician at Université Paris-Dauphine proposed new approach to validate the concept of using a combination of biological, computational and mathematical models and they show how spatial constraints within tumors can be exploited to suppress resistance to targeted therapy.

Lately, mathematical oncologists have designed a new method to tackling this problem based on evolutionary principles. Known as adaptive therapy, this as-yet unproven strategy aims to stop or delay the failure of cancer treatment by manipulating competition between drug-sensitive and resistant cells. It uses relatively low doses and has the additional potential benefits of reducing side effects and enhance quality of life.

As a way to solve the problem, Dr. Noble and Dr. Viossat organized a workshop for mathematical modelers to determine the state of art of adaptive therapy, discuss future directions and foster collaborations. The virtual event was attended by one hundred persons who participated in more than twenty talks, interacting via the Sococo virtual meeting platform.

Dr. Noble plans to continue developing mathematical models to improve cancer treatment. His long-term objective is to project optimal treatment regimens for each tumor type and each patient.

SOURCE

https://medicalxpress.com/news/2021-01-mathematics-approaches-cancer-therapy.html