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How to track the variants of the pandemic faster

Credit: © Oliver Hochstrasser “What scientists have achieved in a year since the discovery of a brand-new virus is truly remarkable,” says Emma Hodcroft from the Institute of Social and Preventive Medicine (ISPM) of the University of Bern, first…

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Credit: © Oliver Hochstrasser

“What scientists have achieved in a year since the discovery of a brand-new virus is truly remarkable,” says Emma Hodcroft from the Institute of Social and Preventive Medicine (ISPM) of the University of Bern, first author on the piece, “but the tools scientists are using to study how SARS-CoV-2 is transmitting and changing were never designed for the unique pressures – or volumes of data – of this pandemic.”

SARS-CoV-2 is now one of the most sequenced pathogens of all time, with over 600,000 full-genome sequences having been generated since the pandemic began, and over 5,000 new sequences coming in from around the world every day. However, the analysis and visualization tools used today (including Nextstrain, co-developed by Prof. Richard Neher’s group at the SIB and the University of Basel) were never designed to handle the volume and speed of sequences being generated today, or the scale of the involvement with public health response. “Across the world, genomic surveillance rests on the initiative of academic researchers to find essential answers. Public health decision making would benefit from a more sustainalble collaboration framework,” says Christophe Dessimoz at SIB and University of Lausanne.

What an improved sequencing would enable

The genetic sequences from SARS-CoV-2 hold valuable information to implementing effective pandemic policies and staying ahead of the virus. Comparing how many mutations different samples share, for example, allows scientists to track the transmission of the virus – helping to identify super-spreading events and international spread. But at the moment it can be hard to combine this genetic information with other key variables – like who attended an event, and when symptoms appeared – which could help make these methods even more informative.

The ‘R-number’ has gone from a scientific concept to a household word in the last year – it measures the average number of people an infected person will transmit to. Here, sequences can help too, by helping to pick apart imported cases from local transmission. This allows for a more accurate estimate of Re, but needs high levels of sequencing and complex analyses, which are currently not widely implemented.

Finally, sequencing is the only way to identify and track the many mutations that arise in SARS-CoV-2. While mutations are a normal part of virus life, scientists need to know which are harmless variations and which could change the virus’ transmissibility or clinical outcome. Combining sequences, lab work, and computational predictions could allow for a better understanding of mutational impacts, but there’s little framework to help these different specialities work together. “The viral data – sequences and associated metadata- must be determined, gathered and harmonized thanks to stable infrastructures compatible with the principles of Open Data to facilitate peer-review by the community and their reuse”, says Christophe Dessimoz at SIB and University of Lausanne, last author of the comment.

Benefits for Switzerland

“In Switzerland, the population could benefit from more systematic and representative sequencing, for example through better contract tracing, targeted isolation and quarantine of smaller regions, and guiding the closing and opening of schools based on the presence of certain variants”, explains Emma Hodcroft. Harmonisation of health data practices is also a critical topic. Switzerland is already putting a lots of efforts at the national level through the Swiss Personalized Health Network (SPHN).

The researchers are convinced that Switzerland’s potential in terms of expertise and infrastructure is just waiting to be tapped, to the benefit of public health. “The tools to enable research are there, and researchers have self-organized and taken the first step: to scale up and sustain these efforts to bring research and public health closer together, we rely on a sustainable public funding”, says Christophe Dessimoz.

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Institute of Social and Preventive Medicine ISPM at the University of Bern

The Institute of Social and Preventive Medicine (ISPM) provides undergraduate and postgraduate education and carries out interdisciplinary research in the fields of social and behavioural health, clinical epidemiology and biostatistics, and international and environmental health. It also provides a wide range of postgraduate education to train students to become excellent public health researchers and to work as public health specialists. This year, the ISPM celebrates its 50th anniversary.

Swiss Institute of Bioinformatics

The SIB Swiss Institute of Bioinformatics is an internationally recognized non-profit organization, dedicated to biological and biomedical data science. Its data scientists are passionate about creating knowledge and solving complex questions in many fields, from biodiversity and evolution to medicine. They provide essential databases and software platforms as well as bioinformatics expertise and services to academic, clinical, and industry groups. SIB federates the Swiss bioinformatics community of some 800 scientists, encouraging collaboration and knowledge sharing.

The institute contributes to keeping Switzerland at the forefront of innovation by fostering progress in biological research and enhancing health.

Data scientists for life
http://www.sib.swiss

Media Contact
Emma Hodcroft PhD, Institute of Social & Preventive Medicine
emma.hodcroft@ispm.unibe.ch

Original Source

https://www.unibe.ch/news/media_news/media_relations_e/media_releases/2021/media_releases_2021/how_to_track_the_variants_of_the_pandemic_faster/index_eng.html

Related Journal Article

http://dx.doi.org/10.1038/d41586-021-00525-x

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Government

Artificial mucus identifies link to tumor formation

NEW ORLEANS, March 18, 2024 – During cold and flu season, excess mucus is a common, unpleasant symptom of illness, but the slippery substance is essential…

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NEW ORLEANS, March 18, 2024 – During cold and flu season, excess mucus is a common, unpleasant symptom of illness, but the slippery substance is essential to human health. To better understand its many roles, researchers synthesized the major component of mucus, the sugar-coated proteins called mucins, and discovered that changing the mucins of healthy cells to resemble those of cancer cells made healthy cells act more cancer-like.

Credit: American Chemical Society

NEW ORLEANS, March 18, 2024 – During cold and flu season, excess mucus is a common, unpleasant symptom of illness, but the slippery substance is essential to human health. To better understand its many roles, researchers synthesized the major component of mucus, the sugar-coated proteins called mucins, and discovered that changing the mucins of healthy cells to resemble those of cancer cells made healthy cells act more cancer-like.

The researcher will present her results today at the spring meeting of the American Chemical Society (ACS). ACS Spring 2024 is a hybrid meeting being held virtually and in person March 17-21; it features nearly 12,000 presentations on a range of science topics.

“For hundreds of years, mucus was considered a waste material or just a simple barrier,” says Jessica Kramer, a professor of biomedical engineering who led the study. And indeed, it does serve as a barrier, regulating the transport of small molecules and particulates to underlying epithelial cells that line the respiratory and digestive tracts. But it also does much more. Studies show that mucus and mucins are biologically active, playing roles in immunity, cell behavior and defense against pathogens and cancer. Kramer’s team at the University of Utah, for example, recently found that specific sugars attached to mucins inhibited coronavirus infection in cell culture.

“Part of the challenge of studying mucus and mucins in general is that they have quite a variety of protein structures,” Kramer explains. Although humans share more than 20 mucin genes, those genes are expressed differently in different tissues and are spliced to generate a range of proteins. In addition, cells modify those proteins in myriad ways with different sugars to meet the body’s needs.

Complicating the picture, genetic factors alone don’t determine mucin composition. Dietary and environmental factors can also influence which sugars become attached to these proteins. Thus, mucus composition can vary significantly from person to person, from day to day, and from tissue to tissue, all of which makes it difficult to identify the biological effects of any given mucin.

To study mucin properties, researchers can collect mucus from animals in slaughterhouses, Kramer says. “But ultimately, it’s quite labor intensive and difficult to purify. And in the process of doing the harvesting, usually the sticky, slimy properties are disrupted.”

As an alternative, mucins can be purchased off-the-shelf, Kramer explains. But because batch-to-batch variability can lead to problems with experimental reproducibility, methods are needed to reliably produce synthetic mucins at scale and at a reasonable price.

In the absence of a simple genetic method to produce individual mucins, Kramer’s lab combined synthetic chemistry and bacterial enzymes to generate the core polypeptides and then selectively add sugars to create unique synthetic mucins. This allows the researchers to test the physical, chemical and biological properties of individual types of mucin molecules and identify the impact of changing individual sugars or protein sequences.

Kramer, along with the lab of collaborator Jody Rosenblatt at King’s College London, is applying her team’s mucins to questions of cancer biology. In particular, the scientists are exploring the influence of mucins on the earliest stages of tumor formation. Previous studies in other labs have shown that mucins embedded in the surface of cancer cells promote metastasis, the spread of cancer to other tissues in the body. These mucins can also help the cancer cells evade immune system defenses by blocking immune cell activation.

“We are building synthetic mucins to understand how the chemical aspects of these proteins affect the behavior of cancer cells,” Kramer explains. “It hasn’t been possible to study these things before because we can’t control the molecular properties of mucins using traditional genetic and biochemical methods.”

Normally, as non-cancerous epithelial cells grow, they crowd together, with some getting eliminated from the epithelial layer to maintain a consistent and stable tissue structure. When Kramer’s team engineered the cells to have a bulky mucin-rich surface similar to that of cancer cells, the cells stopped extruding normally and piled up, forming what looked like the start of tumors.

Kramer is quick to note, however, that her team has not determined whether the genetics of the cells have changed, so they cannot yet state definitively whether the healthy cells were transformed into cancer cells. Those studies are ongoing.

The insights will be pivotal for the development of possible cancer treatments targeting mucins, as they will help highlight which parts of the mucin molecules are most important to tumor formation.

Scientists have been trying to make mucin-targeting therapeutics for decades, but that hasn’t worked well, in part because the sugar groups on the molecules weren’t fully taken into account, Kramer says. “For a vaccine, we can’t only consider the protein sequence because that’s not what the molecule looks like to the immune system. Instead, when an immune cell bumps into the surface of a cancer cell it’s going to see the sugars first, not the protein backbone.” So she believes an effective vaccine will need to target those mucin sugars.

Beyond cancer, the ability to reliably modify the protein sequence and sugars and produce scalable quantities of synthetic mucins offers opportunities to develop these molecules as anti-infectives, probiotics and therapies to support reproductive and women’s health, Kramer says.

The research was funded by the National Institute of General Medical Science, National Science Foundation and Marion Milligan Mason Fund.

Visit the ACS Spring 2024 program to learn more about this presentation, “Synthetic mucins: From new chemical routes to engineered cells,” and more scientific presentations. 

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The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

Note to journalists: Please report that this research was presented at a meeting of the American Chemical Society. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies.

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Title
Synthetic mucins: From new chemical routes to engineered cells

Abstract
Mucin glycoproteins are the major component of mucus and the epithelial glycocalyx. Mucins are essential for life, serving roles as a physical barrier, a lubricant, and a biochemical moderator of infection, immunity, and cancer. There are more than 20 known mucin genes with variable expression patterns, splicing, and post-translational glycosylation patterns. Such diversity has challenged study of structure-function relationships. We are developing scalable methods, based on polymerization of amino acid N-carboxyanhydrides, to synthesize glycan-bearing polypeptides that capture the chemical and physical properties of native mucins. We are utilizing these synthetic mucins to form fully synthetic mucus hydrogels and to engineer the glycocalyx of live cells to shed light on the role of glycans in health and disease. This talk will focus on advances in chemical synthesis along with application of synthetic mucins in study of tumorigenesis.


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Harvard Medical School Professor Was Fired Over Not Getting COVID Vaccine

Harvard Medical School Professor Was Fired Over Not Getting COVID Vaccine

Authored by Zachary Stieber via The Epoch Times (emphasis ours),

A…

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Harvard Medical School Professor Was Fired Over Not Getting COVID Vaccine

Authored by Zachary Stieber via The Epoch Times (emphasis ours),

A Harvard Medical School professor who refused to get a COVID-19 vaccine has been terminated, according to documents reviewed by The Epoch Times.

Martin Kulldorff, epidemiologist and statistician, at his home in Ashford, Conn., on Feb. 11, 2022. (Samira Bouaou/The Epoch Times)

Martin Kulldorff, an epidemiologist, was fired by Mass General Brigham in November 2021 over noncompliance with the hospital’s COVID-19 vaccine mandate after his requests for exemptions from the mandate were denied, according to one document. Mr. Kulldorff was also placed on leave by Harvard Medical School (HMS) because his appointment as professor of medicine there “depends upon” holding a position at the hospital, another document stated.

Mr. Kulldorff asked HMS in late 2023 how he could return to his position and was told he was being fired.

You would need to hold an eligible appointment with a Harvard-affiliated institution for your HMS academic appointment to continue,” Dr. Grace Huang, dean for faculty affairs, told the epidemiologist and biostatistician.

She said the lack of an appointment, combined with college rules that cap leaves of absence at two years, meant he was being terminated.

Mr. Kulldorff disclosed the firing for the first time this month.

“While I can’t comment on the specifics due to employment confidentiality protections that preclude us from doing so, I can confirm that his employment agreement was terminated November 10, 2021,” a spokesperson for Brigham and Women’s Hospital told The Epoch Times via email.

Mass General Brigham granted just 234 exemption requests out of 2,402 received, according to court filings in an ongoing case that alleges discrimination.

The hospital said previously, “We received a number of exemption requests, and each request was carefully considered by a knowledgeable team of reviewers.

A lot of other people received exemptions, but I did not,” Mr. Kulldorff told The Epoch Times.

Mr. Kulldorff was originally hired by HMS but switched departments in 2015 to work at the Department of Medicine at Brigham and Women’s Hospital, which is part of Mass General Brigham and affiliated with HMS.

Harvard Medical School has affiliation agreements with several Boston hospitals which it neither owns nor operationally controls,” an HMS spokesperson told The Epoch Times in an email. “Hospital-based faculty, such as Mr. Kulldorff, are employed by one of the affiliates, not by HMS, and require an active hospital appointment to maintain an academic appointment at Harvard Medical School.”

HMS confirmed that some faculty, who are tenured or on the tenure track, do not require hospital appointments.

Natural Immunity

Before the COVID-19 vaccines became available, Mr. Kulldorff contracted COVID-19. He was hospitalized but eventually recovered.

That gave him a form of protection known as natural immunity. According to a number of studies, including papers from the U.S. Centers for Disease Control and Prevention, natural immunity is better than the protection bestowed by vaccines.

Other studies have found that people with natural immunity face a higher risk of problems after vaccination.

Mr. Kulldorff expressed his concerns about receiving a vaccine in his request for a medical exemption, pointing out a lack of data for vaccinating people who suffer from the same issue he does.

I already had superior infection-acquired immunity; and it was risky to vaccinate me without proper efficacy and safety studies on patients with my type of immune deficiency,” Mr. Kulldorff wrote in an essay.

In his request for a religious exemption, he highlighted an Israel study that was among the first to compare protection after infection to protection after vaccination. Researchers found that the vaccinated had less protection than the naturally immune.

“Having had COVID disease, I have stronger longer lasting immunity than those vaccinated (Gazit et al). Lacking scientific rationale, vaccine mandates are religious dogma, and I request a religious exemption from COVID vaccination,” he wrote.

Both requests were denied.

Mr. Kulldorff is still unvaccinated.

“I had COVID. I had it badly. So I have infection-acquired immunity. So I don’t need the vaccine,” he told The Epoch Times.

Dissenting Voice

Mr. Kulldorff has been a prominent dissenting voice during the COVID-19 pandemic, countering messaging from the government and many doctors that the COVID-19 vaccines were needed, regardless of prior infection.

He spoke out in an op-ed in April 2021, for instance, against requiring people to provide proof of vaccination to attend shows, go to school, and visit restaurants.

The idea that everybody needs to be vaccinated is as scientifically baseless as the idea that nobody does. Covid vaccines are essential for older, high-risk people and their caretakers and advisable for many others. But those who’ve been infected are already immune,” he wrote at the time.

Mr. Kulldorff later co-authored the Great Barrington Declaration, which called for focused protection of people at high risk while removing restrictions for younger, healthy people.

Harsh restrictions such as school closures “will cause irreparable damage” if not lifted, the declaration stated.

The declaration drew criticism from Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, and Dr. Rochelle Walensky, who became the head of the CDC, among others.

In a competing document, Dr. Walensky and others said that “relying upon immunity from natural infections for COVID-19 is flawed” and that “uncontrolled transmission in younger people risks significant morbidity(3) and mortality across the whole population.”

“Those who are pushing these vaccine mandates and vaccine passports—vaccine fanatics, I would call them—to me they have done much more damage during this one year than the anti-vaxxers have done in two decades,” Mr. Kulldorff later said in an EpochTV interview. “I would even say that these vaccine fanatics, they are the biggest anti-vaxxers that we have right now. They’re doing so much more damage to vaccine confidence than anybody else.

Surveys indicate that people have less trust now in the CDC and other health institutions than before the pandemic, and data from the CDC and elsewhere show that fewer people are receiving the new COVID-19 vaccines and other shots.

Support

The disclosure that Mr. Kulldorff was fired drew criticism of Harvard and support for Mr. Kulldorff.

The termination “is a massive and incomprehensible injustice,” Dr. Aaron Kheriaty, an ethics expert who was fired from the University of California–Irvine School of Medicine for not getting a COVID-19 vaccine because he had natural immunity, said on X.

The academy is full of people who declined vaccines—mostly with dubious exemptions—and yet Harvard fires the one professor who happens to speak out against government policies.” Dr. Vinay Prasad, an epidemiologist at the University of California–San Francisco, wrote in a blog post. “It looks like Harvard has weaponized its policies and selectively enforces them.”

A petition to reinstate Mr. Kulldorff has garnered more than 1,800 signatures.

Some other doctors said the decision to let Mr. Kulldorff go was correct.

“Actions have consequence,” Dr. Alastair McAlpine, a Canadian doctor, wrote on X. He said Mr. Kulldorff had “publicly undermine[d] public health.”

Tyler Durden Sat, 03/16/2024 - 21:00

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International

“Extreme Events”: US Cancer Deaths Spiked In 2021 And 2022 In “Large Excess Over Trend”

"Extreme Events": US Cancer Deaths Spiked In 2021 And 2022 In "Large Excess Over Trend"

Cancer deaths in the United States spiked in 2021…

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"Extreme Events": US Cancer Deaths Spiked In 2021 And 2022 In "Large Excess Over Trend"

Cancer deaths in the United States spiked in 2021 and 2022 among 15-44 year-olds "in large excess over trend," marking jumps of 5.6% and 7.9% respectively vs. a rise of 1.7% in 2020, according to a new preprint study from deep-dive research firm, Phinance Technologies.

Algeria, Carlos et. al "US -Death Trends for Neoplasms ICD codes: C00-D48, Ages 15-44", ResearchGate, March. 2024 P. 7

Extreme Events

The report, which relies on data from the CDC, paints a troubling picture.

"We show a rise in excess mortality from neoplasms reported as underlying cause of death, which started in 2020 (1.7%) and accelerated substantially in 2021 (5.6%) and 2022 (7.9%). The increase in excess mortality in both 2021 (Z-score of 11.8) and 2022 (Z-score of 16.5) are highly statistically significant (extreme events)," according to the authors.

That said, co-author, David Wiseman, PhD (who has 86 publications to his name), leaves the cause an open question - suggesting it could either be a "novel phenomenon," Covid-19, or the Covid-19 vaccine.

"The results indicate that from 2021 a novel phenomenon leading to increased neoplasm deaths appears to be present in individuals aged 15 to 44 in the US," reads the report.

The authors suggest that the cause may be the result of "an unexpected rise in the incidence of rapidly growing fatal cancers," and/or "a reduction in survival in existing cancer cases."

They also address the possibility that "access to utilization of cancer screening and treatment" may be a factor - the notion that pandemic-era lockdowns resulted in fewer visits to the doctor. Also noted is that "Cancers tend to be slowly-developing diseases with remarkably stable death rates and only small variations over time," which makes "any temporal association between a possible explanatory factor (such as COVID-19, the novel COVID-19 vaccines, or other factor(s)) difficult to establish."

That said, a ZeroHedge review of the CDC data reveals that it does not provide information on duration of illness prior to death - so while it's not mentioned in the preprint, it can't rule out so-called 'turbo cancers' - reportedly rapidly developing cancers, the existence of which has been largely anecdotal (and widely refuted by the usual suspects).

While the Phinance report is extremely careful not to draw conclusions, researcher "Ethical Skeptic" kicked the barn door open in a Thursday post on X - showing a strong correlation between "cancer incidence & mortality" coinciding with the rollout of the Covid mRNA vaccine.

Phinance principal Ed Dowd commented on the post, noting that "Cancer is suddenly an accelerating growth industry!"

Continued:

Bottom line - hard data is showing alarming trends, which the CDC and other agencies have a requirement to explore and answer truthfully - and people are asking #WhereIsTheCDC.

We aren't holding our breath.

Wiseman, meanwhile, points out that Pfizer and several other companies are making "significant investments in cancer drugs, post COVID."

Phinance

We've featured several of Phinance's self-funded deep dives into pandemic data that nobody else is doing. If you'd like to support them, click here.

 

Tyler Durden Sat, 03/16/2024 - 16:55

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