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Category Archives: Molecular Medicine

Dr. Scott on the Incorporation of GARD-Based Radiotherapy Dosing in Oncology – OncLive

Posted: August 31, 2021 at 2:02 am

Jacob G. Scott, MD, DPhil, discusses the incorporation of genomic-adjusted radiation dosebased radiotherapy dosing in oncology.

Jacob G. Scott, MD, DPhil, associate staff, Departments of Translational Hematology and Oncology Research and Radiation Oncology, Cleveland Clinic, clinical assistant professor, Department of Molecular Medicine, adjunct assistant professor, Department of Physics, Case Western Reserve University School of Medicine, member, Development Therapeutics Program, Case Comprehensive Cancer Center, Case Western Reserve University, discusses the incorporation of genomic-adjusted radiation dose (GARD)based radiotherapy dosing in oncology.

Although it can be difficult to define levels of evidence in biomarker studies based on archival tissue specimens, GARD-based radiotherapy dosing is backed by level 1 evidence and is potentially ready for use in clinical practice, Scott says. However, incorporating a clinical decision support tool will require some relearning of practice standards, which have always been based on empirical evidence from dose-escalation trials, Scott explains.

The tool, which is similar to an oncotype assay, supports the idea that quantifying the biological effect of radiotherapy with GARD is associated with time to first recurrence and overall survival for patients with cancer who undergo radiation treatment. Moreover, GARD-based dosing is predictive of benefit with radiation therapy, Scott concludes.

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Delta is the major variant in the Western Province – J’pura University report – Newsfirst.lk

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COLOMBO (News 1st): Four mutations of COVID-19 Delta Variant were found in Western Province, researchers at the University of Sri Jayawardenapura said.

University of Sri Jayawardenapura researchers including Prof. Neelika Malavige, Dr. Chandima Jeewandara from the Allergy, Immunology and Cell Biology Unit of the Department of Immunology Molecular and Molecular Medicine released a report confirming the discovery of Delta variant with four mutations within the Western Province itself.

The report states that out of the four mutations, 2 mutations (A701S, R24C) are found only in Sri Lanka and one mutation (A1078S) was present only in Malaysia and Sri Lanka, while the other mutation (A222V) is the common delta variant present in many other countries.

Out of the 94 samples for the research, the areas Colombo (CMC and various areas, Hanwella, Kaduwela), Nuwaraeliya (Bogawantalawa, Dikoya, Lindula), Embilipitiya, Matara (Dickwella, ), Gampaha (Ganemulla, Makola, Ragama, Weyangoda), Kegalle, Point Pedro, Puliyakulam and Vaviniya have been identified as Delta variant infected areas.

Moreover, only 3 samples of the alpha variant [B.1.1.7 (alpha)] have been identified from Anuradhapura, Bohawantalaka and Kandawalai.

Accordingly, the major variant spreading in the Colombo District, the Delta variant, has spread to other Districts of the country as well.

The researchers observed that the frequency of the mutated delta appears to increase over the time, suggesting that it could be more transmissible than the original Delta (delta without these 4 mutations). However more data is required for the researchers to conclude.

While the vast majority of viruses have been sequenced in the Colombo district, sequencing has been carried out from many areas from all over Sri Lanka.

USJ researchers found Four mutant Covid Delta variants with two new Sri Lankan mutations (A701S, R24C) USJ University of Sri Jayewardenepura, Sri Lanka (sjp.ac.lk)

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NIH launches study of extra COVID-19 vaccine dose in people with autoimmune disease – National Institutes of Health

Posted: at 2:02 am

News Release

Friday, August 27, 2021

Trial also will test pausing immunosuppressive medication to improve antibody response.

The National Institutes of Health has begun a clinical trial to assess the antibody response to an extra dose of an authorized or approved COVID-19 vaccine in people with autoimmune disease who did not respond to an original COVID-19 vaccine regimen. The trial also will investigate whether pausing immunosuppressive therapy for autoimmune disease improves the antibody response to an extra dose of a COVID-19 vaccine in this population. The Phase 2 trial is sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, and is being conducted by the NIAID-funded Autoimmunity Centers of Excellence.

Many people who have an autoimmune disease that requires immunosuppressive therapy have had a poor immune response to the authorized and approved COVID-19 vaccines, placing these individuals at high risk for the disease, said NIAID Director Anthony S. Fauci, M.D. We are determined to find ways to elicit a protective immune response to the vaccines in this population. This new study is an important step in that direction.

An estimated 8% of Americans have an autoimmune disease, including a disproportionate number of people in the minority communities most severely impacted by COVID-19. Researchers have reported higher rates of severe COVID-19 and death in people with autoimmune disease than in the general population. It is unclear whether this is attributable to the autoimmune disease, the immunosuppressive medications taken to treat it, or both.

The results of recent studies indicate that giving an extra dose of an authorized COVID-19 vaccine to solid organ transplant recipients, who must take immunosuppressive medications, can improve the immune response to the vaccine in many of these individuals. A NIAID study is underway to investigate this further. The recent findings in solid organ transplant recipients also suggest that an extra dose of a COVID-19 vaccine may help some people with autoimmune disease who take certain immunosuppressive medications. The Food and Drug Administration recently amended the emergency use authorizations for the Pfizer-BioNTech and Moderna COVID-19 vaccines to allow the administration of an additional dose to solid organ transplant recipients and other people who have an equivalent level of immunocompromise.

The new NIAID trial, called COVID19 Booster Vaccine in Autoimmune Disease NonResponders, initially will include people with one of five autoimmune diseases: multiple sclerosis, pemphigus, rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis. The immunosuppressive therapies commonly taken by people with these diseases have been associated with poor immune responses to vaccines.

The study team will enroll approximately 600 participants ages 18 years and older at 15 to 20 sites nationwide. Participants must have had a negative or suboptimal antibody response to two doses of the Moderna COVID-19 vaccine, two doses of the Pfizer-BioNTech COVID-19 vaccine, or one dose of the Johnson & Johnson COVID-19 vaccine, all received prior to enrollment. Participants also must be taking one of three immunosuppressive therapies: mycophenolate mofetil (MMF) or mycophenolic acid (MPA); methotrexate (MTX); or B cell- depleting drugs.

All participants will receive an extra dose of the same COVID-19 vaccine as they received originally. Then those participants who are taking MMF/MPA or MTX will be assigned at random either to continue taking their immunosuppressive medication without alteration or to pause taking their medication for a short period before and after receiving the extra vaccine dose. The main goal of the study is to determine the proportion of participants who have a significantly better antibody response four weeks after receiving the extra vaccine dose than they did after their original vaccinations.

Study participants will be followed for a total of 13 months. Preliminary results are expected in November 2021.

The COVID19 Booster Vaccine in Autoimmune Disease NonResponders trial is being led by Judith James, M.D., Ph.D., Meggan Mackay, M.D., M.S., Dinesh Khanna, M.B.B.S., M.Sc., and Amit Bar-Or, M.D., F.R.C.P.C. Dr. James is vice president of clinical affairs and program chair of the Arthritis & Clinical Immunology research program at the Oklahoma Medical Research Foundation in Oklahoma City. Dr. Mackay is a professor in the Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York. Dr. Khanna is the Frederick G.L. Huetwell professor of rheumatology and the director of the scleroderma program in the department of internal medicine at University of Michigan in Ann Arbor. Dr. Bar-Or is the director of the Center for Neuroinflammation and Neurotherapeutics, chief of the multiple sclerosis division, and the Melissa and Paul Anderson President's Distinguished Professor at the University of Pennsylvania in Philadelphia.

Additional information about the COVID19 Booster Vaccine in Autoimmune Disease NonResponders trial, including the locations of study sites, is available in ClinicalTrials.gov under study identifier NCT05000216.

NIAID conducts and supports researchat NIH, throughout the United States, and worldwideto study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing, and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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Largest Study of Long COVID Points to an Alarming Prognosis – BioSpace

Posted: at 2:02 am

The body of real-world evidencearound COVID-19 continues to build, and a study released Thursday in The Lancet points to concerning long-term effects for hospital survivors at the one-year mark.

The study, which was led by Dr. Bin Cao from the China-Japan Friendship Hospital in Beijing, is a head-to-head comparison of 1,276 people discharged from Jin Yin-Tan Hospital in Wuhan between January and May 2020 and comparable Wuhan residents who were not infected with COVID-19. In what is the largest paper of its kind yet to be published, the former patients were assessed at both six and 12 months following the onset of their first symptoms.

Common long-term effects suffered by COVID-19 survivors include fatigue, muscle weakness, sleep disturbances, changes in taste and smell, dizziness, headache and shortness of breath. At the six-month mark, 68% of participants reported at least one persistent symptom, which fell to 49% after one year. In all, the former patients self-reported experiencing a lower quality of life than their counterparts, and the most common maladies were fatigue and muscle weakness.

Reflective of the enigma that is COVID-19, the number of patients reporting breathing problems actually increased between the six and 12-month check-ins from 26% to 30%, while the percentage of people who felt anxious or depressed rose from 23% at six months to 30% at one year. Both mental and physical health challenges were especially prevalent among those who had experienced the most serious disease.

That people would still be in a rehabilitation period after 12 months is outside of the norm for David Putrino, director of rehabilitation innovation at Mount Sinai Health Systems in New York. Putrino told TIME that this is not an example of a glass-half-full story.

After most hospital stays, including for, say, walking pneumonia, I would not be expecting people at 12 months to still be reporting symptoms to me, said Putrino, who oversees the networks Long COVID rehabilitation program.

According to Putrino, being fortunate enough to escape hospitalization may not guarantee a full immediate recovery.

This virus doesnt end once you get discharged from the hospital or once you get over the initial acute symptoms, he said, referencing smaller studies showing that symptoms may linger in around 20% of these patients.

These studies could spell bad news for a lot of survivors. According to a collection of four international studies published in late July, there are more than 200 possible Long COVID symptoms. In one paper, researchers assessed responses from 3,762 patients from 56 countries with either confirmed or suspected COVID-19 and found an average of 56 reported symptoms across 9 different organ systems. More than 91% of these patients required at least 35 weeks to recover. The most commonly reported symptoms after six months were fatigue, post-exertional malaise, and cognitive disfunction.

It appears that even vaccination is not a complete get out of jail free card in every case when it comes to preventing Long COVID. In an Israeli study of 1,497 vaccinated health care workers, 39 became infected regardless, and 7 of those individuals experienced symptoms that lasted at least six weeks.

"We had hoped that when you get vaccinated and even if you did have a breakthrough infection you would have enough of an immune response that would block this protracted symptom complex now known as long COVID, said Dr. Eric Topol, a professor of molecular medicine at Scripps Research. This study is the really first to give us an indicator that there's some long-haulers among that small group of people that had breakthrough infections.

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Genome Medical Announces Acquisition of GeneMatters and Closing of $60 Million Series C Financing – Business Wire

Posted: at 2:02 am

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genome Medical, the leading nationwide genomic care delivery company, today announced that it will acquire GeneMatters, a telehealth genetic counseling and software solutions company. Simultaneously, the company announced the closing of a $60 million Series C financing to accelerate commercial traction and advance its mission of transforming health care for all through genomic medicine. These strategic initiatives solidify its position as the preeminent technology-enabled provider of genetic health services and genomic insights.

The addition of GeneMatters, along with our Series C financing, propels us into the next phase of commercial growth and enables us to realize the genome-driven personalization of health, said Lisa Alderson, co-founder and CEO of Genome Medical. The genomic medicine industry is primed with testing capabilities and novel therapeutics; now is clearly the moment for Genome Medical to deliver expanded availability of genomic medicine for patients and providers.

Genome Medical will use the financing proceeds to expand its team and further enhance the development of its configurable technology solutions to provide innovative and efficient genomic medicine programs. The company will continue to build out its full suite of physician services, test ordering capabilities and guidelines-based care plans to ensure comprehensive, seamless care for patients.

The Series C round was led by Casdin Capital, a committed and leading long-term investor in life sciences and genomics, and was joined by new investors GV (formerly Google Ventures) and Amgen Ventures. Existing investors also participated, including Perceptive Advisors, Canaan Partners, Kaiser Permanente Ventures, Illumina Ventures, LRVHealth, Echo Health Ventures, Revelation Partners, HealthInvest Equity Partners, Avestria Ventures, Flywheel Ventures, Dreamers Fund and Blue Ivy Ventures.

In connection with the financing, the Genome Medical Board of Directors will be joined by Eli Casdin, founder and chief investment officer at Casdin Capital; Shaun Rodriguez, director of life science research at Casdin Capital; and Jill Davies, co-founder and president of GeneMatters. Anthony Philippakis, M.D., Ph.D., venture partner at GV, will join the board as an observer.

We feel fortunate to have been in the unique position to facilitate this strategic combination of two strong genomic health providers and Casdin portfolio companies, Eli Casdin said. We have been an early and active investor in the development of genetic testing capabilities broadly. The breadth and scale of Genome Medical and GeneMatters together produce the clear leader in digital health for genomics. It is also a terrific example of how one + one can equal more than two!

Together, Genome Medical and GeneMatters represent expanded technology solutions and clinical expertise to better meet the growing need for genomic medicine across health and wellness. GeneMatters will operate as a wholly owned subsidiary of Genome Medical Holding Company, with a focus on expanding the delivery of genetic services to community health systems and other partners.

The mission of GeneMatters from day one has been to increase patient access to genetic services and to support patient decision-making, said GeneMatters Davies. Joining the Genome Medical family allows for expanded capabilities, broader reach and ultimately more patients and providers being served. We are thrilled to be joining forces with this talented team that shares our mission, vision and passion for patient care.

By combining innovative, technology-enabled solutions with the virtual delivery of industry-leading clinical expertise, Genome Medical is accelerating the adoption of genetic services and genomic medicine for health care systems, large-scale research studies, health plans, employers, providers and molecular diagnostic testing laboratories. Learn more about Genome Medicals comprehensive services, including its Genome Care DeliveryTM platform and precision insights for population genomics.

About Genome Medical

Genome Medical, the leading genomic care delivery company, is personalizing health care for all through on-demand access to genetic insights and genomic medicine. We operate as an independent virtual medical practice, powered by a digital health technology platform. By partnering with health systems, providers, health plans, employers, labs and biopharma, we expand the reach and impact of precision medicine. We provide clinical assessments and tools, test recommendations and ordering, and personalized care plans to deliver optimal patient care and improve health outcomes. The company, which is headquartered in South San Francisco, was recently honored as The Best Digital Health Company to Work For by Rock Health, Fenwick & West and Goldman Sachs in their Top 50 in Digital Health awards. To learn more, visit genomemedical.com and follow @GenomeMed.

About GeneMatters

GeneMatters is a leading provider of telehealth genetic counseling and software solutions to increase access to genetic services. We deliver customizable solutions to hospitals, health networks, genetic testing labs and biopharmaceutical organizations to extend the capacity of existing genetic counseling teams, support new programs and increase patient engagement with genetic services. Our genetic expertise spans oncology, reproductive, cardiovascular and rare diseases. Founded in 2016 by Jill Davies, a genetic counselor, with a mission to increase patient access, we are committed to outstanding service delivery, unwavering quality standards, high patient satisfaction and technology to simplify care. To learn more, visit gene-matters.com and follow @GeneMatters on Twitter Linkedin

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Does the explosion of the delta variant mean we need a new COVID-19 vaccine? – Livescience.com

Posted: August 18, 2021 at 2:03 am

The rapid spread of the delta variant of SARS-CoV-2 has put more patients in hospital beds and led to reinstatements of mask mandates in some cities and states. The variant, which is more transmissible than previous variants, also seems more able to cause breakthrough infections in vaccinated people.

Fortunately, vaccines are forming a bulwark against severe disease, hospitalization and death. But with the specter of delta and the potential for new variants to emerge, is it time for booster shots or even a new COVID vaccine?

For now, public health experts say the far bigger emergency is getting first and second doses into people who haven't had a single shot. Most people don't need boosters to prevent severe illness, and it's not clear when or if they will. But companies are already looking into updating their vaccines for coronavirus mutations, and there is a good chance that third shots are coming soon for some people. Already, the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) have greenlighted booster shots for immunocompromised individuals.

Related: Coronavirus variants: Here's how the SARS-CoV-2 mutants stack up

"I think we're looking at an inevitable move toward boosters, at least in higher-risk people like those of advanced age and obviously the immunocompromised," said Dr. Eric Topol, a professor of molecular medicine at The Scripps Research Institute in California.

Vaccine developers are working on the question of whether future COVID-19 shots will need to be tweaked for the delta variant, or other new variants. For now though, initial evidence hints that boosters of the original vaccine should add protection against delta.

While all the COVID-19 vaccines in the U.S. are doing a fabulous job of preventing severe disease and death, it's clear that breakthrough infections are more common with this variant. Data on efficacy is still emerging, and efficacy is a moving target depending on a lot of factors. It's hard to make apples-to-apples comparisons between countries or hospital systems, said Jordi Ochando, an immunologist and cancer biologist at the Icahn School of Medicine at Mount Sinai. Different countries have different levels of vaccination, have used different vaccine mixes with different dose scheduling, and have different populations with different age stratification, comorbidities and levels of previous infection.

Still, synthesizing data from different countries suggests the mRNA vaccines by Pfizer-BioNTech and Moderna are probably up to 60% or as low as 50% protective against infection with delta, Topol wrote on Twitter. That's right on the border of efficacy at which the Food and Drug Administration would approve a new COVID-19 vaccine. The J&J vaccine is probably less protective against symptomatic illness than a two-dose mRNA vaccine, based on studies finding that it elicits lower levels of neutralizing antibodies (which block the virus from entering cells).

Data is now emerging that the J&J vaccine likely prevents severe disease from delta as well. Though people with symptomatic breakthrough infections can spread the delta variant, the vaccines do still seem to reduce the likelihood of transmission by making any infection that does occur shorter. A study conducted in Singaporefound that viral load started at similar levels in vaccinated and unvaccinated individuals who were infected with delta, but it dropped much faster in vaccinated individuals, beginning a steeper decline around day 5 or 6 of illness. This could mean that vaccination shortens the infectious period. However, more confirmation is necessary to show whether the Singapore results will hold up. The discovery that vaccinated people can have viable virus in their noses if infected is what made the CDC reverse its recommendation that vaccinated people did not need to wear masks.

It's not clear exactly why delta can break through vaccine-induced protection more frequently, but there may be multiple factors at play. One is that the antibodies that the vaccine elicits may not bind to the virus variant as well. Delta appears to have spike mutation proteins that make original coronavirus antibodies a worse fit, according to research published in Nature in July. This means that previously infected and vaccinated people have antibodies that aren't quite as protective against delta as they were against the original or alpha variants, said Yiska Weisblum, a postdoctoral researcher in retrovirology at The Rockefeller University in New York.

Another possible reason for waning efficacy is that the immune system starts letting down its guard over time. This happens with the pertussis vaccine, which is why expectant parents and other adults who are going to be around unvaccinated newborns should get booster shots.

"Right now, the U.S. is the driver of the world delta wave, and we are the leading force of nurturing new variants, because it's out of control here."

Whether waning immunity is likely to be a problem for COVID-19 vaccines is currently a hot topic among researchers. Israeli health authorities say they've seen an increase in breakthrough infections in people immunized in January versus March and are concerned about an uptick in more severe breakthrough cases in those 60 and older, according to Haaretz.

Data from an Israeli HMO published on the preprint server medRxiv before peer review found that 2% of people who requested a PCR test for any reason post-vaccination received a positive result. People vaccinated more than 146 days before being tested were twice as likely to experience a breakthrough infection. The vast majority of the cases in the study were delta. It's difficult to track waning immunity because you need to revisit the same group of people over time, tracking their infection status, Scripps' Topol told Live Science. That kind of data hasn't really emerged yet. But Topol said he's transitioned from skepticism over waning immunity to belief that it is occurring.

"It does look like there is a substantial interaction with delta finding people who are several months out from when they got fully vaccinated," Topol said. "It's a double hit. If you were six months out, and there is no delta, you're probably fine. The problem is this interaction."

Delta's ability to infect the fully vaccinated raises questions about the best strategy going forward. One option would be to give a booster of the same vaccine, raising antibody levels to what scientists hope will be protective levels against delta.

Vaccine manufacturers are also studying versions of the vaccines that update the spike protein targeted by their vaccines.

But trying to play catch-up with delta-specific vaccines might be akin to a game of whack-a-mole, said Dr. Krutika Kuppalli, an infectious disease specialist at the Medical University of South Carolina. There was talk of updating the mRNA vaccines with a spike protein specific to the alpha variant, Kuppalli told Live Science. Now, of course, alpha is vanishing on its own, being replaced by the far more transmissible delta.

"By the time [a new vaccine] might even be ready then we're on to the next one," Kuppalli said.

Related: 14 coronavirus myths busted by science

If delta has taught us anything, it's that ideally, a future SARS-CoV-2 vaccine wouldn't be delta-specific, but rather universal to all potential SARS-CoV lineages, Topol said. A universal vaccine could draw on similarities between the viruses SARS-1, which emerged in 2003, is genetically 95% similar to SARS-CoV-2, after all and be reverse-engineered to produce potent antibodies seen in some people infected with SARS viruses, Topol said.

"We could get there soon," Topol said. "That would hopefully be an enduring solution rather than an 'each Greek letter' solution." (Each new coronavirus variant of concern gets a new Greek letter name.)

Another promising notion is that of a needle-free, nasal spray vaccine against COVID-19. Nasal vaccines deliver directly to the spot where the virus lands and elicit immunity right in the mucous membrane that lines the nose. This mucosal immunity can combat the virus quickly, reducing viral replication in the nose, and thus tamping down viral shedding and transmission, University of Alabama at Birmingham researchers wrote July 23 in the journal Science.

A more immediate option might be to harness the advantages of having multiple approved vaccines, said Mount Sinai's Ochando. Mixing and matching vaccines seems to give an immunological boost over boosters of the same time, Ochando told Live Science, citing several papers published in The Lancet.

But even a booster of the original vaccine is likely to help improve immunity against delta. Weisblum and her colleagues have found that people who were infected with SARS-CoV-2 before delta became predominant and then got fully vaccinated have a broader array of antibodies than those who were only infected or those who were only vaccinated. This suggests that when the body sees some version of SARS-CoV-2 three times, it mounts a broader campaign against the invader strong enough to take down even the delta variant. The researchers even tested these triple-strength antibodies against a spike protein mutated in the lab to resist antibodies from infection or vaccination and found that they conquered this multiple-mutant spike.

"This data suggests that boosting definitely has the potential to increase the breadth of our antibody responses," Weisblum wrote in an email to Live Science. "It also suggests that boosting with the wild type original virus spike could be good enough (since the convalescent vaccinated individuals only saw the original spike), but updating the vaccine to mimic circulating or potentially emerging variants should increase the breadth of the response even more."

One reason the future of COVID-19 vaccines against new variants is hard to understand is that scientists aren't yet sure which immune cells best represent vaccine efficacy in the long term. Most studies now look at neutralizing antibodies. These are a good proxy for protection against infection, said Dr. Zain Chagla, an infectious disease specialist at McMaster University, but may not be as good a representation against protection against severe disease. That's because the immune system recruits a bevy of other cellular protectors such as B cells and T cells to fight once a virus invades. These defenses aren't as quick to the punch as neutralizing antibodies, but they can prevent an infection from turning serious.

Over time, though, antibodies decline (if they didn't, your blood would turn into a sluggish goo of antibodies), while long-term immune cells such as memory B cells and plasma cells persist, ready to mount a new response should the virus reappear again. One challenge for assessing vaccine efficacy going forward will be figuring out which sorts of immune cells to measure to determine how protected someone is from disease after antibody levels decline.

For diseases like hepatitis and measles, researchers have determined a cutoff for an antibody level that provides protection, Chagla said. "As long as you're over that cutoff, it tends to predict success or failure better than just, 'higher is better,'" he said.

There may be a similar cutoff for coronavirus antibodies, but researchers don't know what it is yet.

The trouble with waiting for this data, Ochando said, is that scientists have to study reinfections as they happen. Allowing reinfections opens up the possibility of allowing for more transmission, severe illness and spread. Thus, boosters might be ethically necessary as a precaution, even without rigorous clinical trials delineating their efficacy, Ochando said.

If a third dose of an existing or new formulation of COVID-19 vaccine proves necessary, it doesn't necessarily follow that everyone will need a COVID-19 shot every six months to a year for the rest of their lives. Some vaccines, like the Hepatitis B vaccine, perform best with a 3-dose series, after which there's rarely a need for a booster. It might be that three doses of an mRNA shot at the right spacing will provide strong and long-lasting protection, Cline Gounder, an infectious disease specialist and epidemiologist at the New York University Grossman School of Medicine, said on Twitter.

Whatever the data ultimately shows about the need for boosters, the real bang for the vaccination buck still lies in first shots, not third shots, Kuppalli told Live Science. Facing COVID-19 unvaccinated is much more dangerous than facing it fully vaccinated, and the continued circulation of the virus around the globe just means more opportunity for mutations that could benefit the virus.

"Right now, the U.S. is the driver of the world delta wave, and we are the leading force of nurturing new variants, because it's out of control here," Topol said.

The danger of being unvaccinated is global. Worldwide, only 15.6% of people are fully vaccinated, according to Our World in Data. This has many health experts concerned that high-income countries will be busy handing out booster shots while the rest of the world burns. It's another ethical quandary, Ochando said. Distributing booster shots to the immunocompromised and elderly in wealthy countries makes sense, he told Live Science, but providing third shots to young, healthy people in rich countries is hard to swallow when only 2% of Africa's population has been fully vaccinated, according to the Africa Centres for Disease Control numbers.

Kuppalli agreed.

"I understand countries want to take care of their own, but I think we need leaders to step back and look at the global picture and look at why we are in this continued cycle and look at why these variants keep emerging," Kuppalli told Live Science. "And the reason the variants keep emerging is we are unable to keep the global rate of the virus down."

Originally published on Live Science.

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Feinstein Institutes Bioelectronic Medicine Researchers Control Nerve to Turn On/Off Inflammation – Business Wire

Posted: at 2:03 am

MANHASSET, N.Y.--(BUSINESS WIRE)--In an effort to better understand inflammation within the body, researchers at The Feinstein Institutes for Medical Research the global scientific home of bioelectronic medicine successfully controlled the neurons that release molecular proteins and turn on/off inflammation. The preclinical research recently published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS). The study points to a new approach to treat diseases such as arthritis, which are characterized by inflammation and pain.

Inflammation is the bodys defense response to injury and infection triggered by molecular proteins, such as high mobility group box 1 protein (HMGB1). These molecules also stimulate sensory neurons, termed nociceptors. Activation of nociceptors controls the inflammation through release of neuropeptides producing neuroinflammation. While important, if unresolved inflammation can be harmful, resulting in autoimmune or autoinflammatory disorders like rheumatoid arthritis or Crohns disease.

Using light or genetic tools, we can turn off and on the switch that controls inflammation in the body, said Sangeeta S. Chavan, PhD, professor in the Institute of Bioelectronic Medicine at the Feinstein Institutes. This preclinical bioelectronic medicine research is paving the way for a variety of new treatment options for people living with serious, chronic health conditions.

The study, led by Dr. Chavan and associate professor Huan Yang, PhD, combines optogenetics, neuronal-specific deletion (or removal) and preclinical models of inflammatory diseases while monitoring inflammation and neuropathic pain. The results show that nociceptor HMGB1 is required for a neuroinflammatory response to injury. These experiments provide direct evidence that nociceptor-related pain can be prevented by targeting HMGB1 a potential therapy of neuroinflammatory diseases.

Our new methodology allows us to develop ways to regulate inflammation mediated by neurons, said Dr. Yang. The optogenetic and neuronal-specific ablation strategies show us the critical role HMGB1 plays in neuroinflammation and pain.

The results show that a new paradigm for nervous system integration of environmental signals to stimulate inflammation is fundamental to spark an immune system defense during infection and injury. The research suggests that targeting HMGB1 may constitute a new therapeutic approach for treating a variety of diseases.

After 30 years of researchers studying how to turn off the immune system, we recently sought a way to turn it on, said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes. Thanks to this pivot in research, Drs. Yang and Chavan discovered that nerves release a molecule to produce inflammation in the body, which could lead to a new strategy to develop pharmaceutical and bioelectronic therapies.

Dr. Chavan and the Institute of Bioelectronic Medicine continue to advance this emerging field of science which combines molecular medicine, neuroscience and bioengineering to study how to use devices to treat diseases and injury. Dr. Chavan reported in a 2020 study also published in PNAS, the discovery of a small cluster of neurons within the brain that is responsible for controlling the bodys immune response and the release of cytokines, which leads to inflammation in the body.

About the Feinstein Institutes

The Feinstein Institutes for Medical Research is the research arm of Northwell Health, the largest health care provider and private employer in New York State. Home to 50 research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its five institutes of behavioral science, bioelectronic medicine, cancer, health innovations and outcomes, and molecular medicine. We make breakthroughs in genetics, oncology, brain research, mental health, autoimmunity, and are the global scientific leader in bioelectronic medicine a new field of science that has the potential to revolutionize medicine. For more information about how we produce knowledge to cure disease, visit http://feinstein.northwell.edu and follow us on LinkedIn.

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Feinstein Institutes Bioelectronic Medicine Researchers Control Nerve to Turn On/Off Inflammation - Business Wire

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Beware the ‘molecular parasites’ involved in aging and disease – Brown University

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PROVIDENCE, R.I.[Brown University] If youve ever seen a petunia with artfully variegated petals, then youve seen transposons at work. The flowers showy color patterns are due to transposable elements, or DNA sequences that can move locations within a genome. Yet when it comes to transposons effects on humans, the results might not be as lovely or desirable.

As researchers learn more about these so-called mobile genetic elements, theyve found increasing evidence that transposons influence and even promote aging and age-related diseases like cancer as well as neurogenerative and autoimmune disorders, says John Sedivy, a professor of biology and director of the Center on the Biology of Aging at Brown. Sedivy is the corresponding author of a new review article in Nature that discusses the latest thinking and research around transposons.

The splotches and specks of this variety of flower, petunia hybrida W138, are due to the activity of transposons. (Photo: The Petunia Platform, ENS de Lyon)

Lets put it this way: These things can be pretty dangerous, said Sedivy. If they are uncontrolled, and there are many examples of that, transposons can have profound consequences on most forms of life that we know of.

Since the dawn of life, the researchers noted, transposons have coevolved with their host genomes, but its been more of a competitive existence than a peaceful one, earning them the nicknames of junk DNA and molecular parasites. Transposons were first discovered in corn by the Nobel prize-winning geneticist Barbara McClintock in the 1940s, who also found that depending on where they inserted into a chromosome, they could reversibly alter the expression of other genes.

It is now quite apparent that the genomes of virtually all organisms, including humans, contain repetitive sequences generated by the activity of transposons. When these elements move from one chromosome or part of a chromosome to another, they amplify and increase their presence in genomes, sometimes to dramatic levels. According to Sedivy, about half of the human genome is due to the activity of these molecular parasites. Their unregulated activity can have long-term benefits by increasing genetic diversity in organisms, but in most cases the chaos degrades cell function, such as by disrupting useful genes.

Most of what is known about transposons, said Sedivy, comes from genome sequence data that shows their activity in the germline, or throughout successive generations of an organism. However, recent research, including from Sedivy and other scientists at Brown, has revealed a wealth of information on transposon activity during the lifetime of a single individual, as well.

In an interview, Sedivy discussed the mechanisms driving transposons, how their activity influences and promotes age-related tissue degeneration and disease and what can be done to fight back.

There are two main groups: 'DNA transposons' move using a DNA intermediate in a 'cut and paste' mechanism, and retrotransposons move using a 'copy and paste' mechanism that involves an RNA intermediate. Thirty five percent of the human genome is comprised of retrotransposon DNA sequences. The reason they move is to survive; it allows them to relocate to and increase their presence in their hosts. You can think of transposons as viruses there are some viruses that are, in fact, transposable elements. HIV (human immunodeficiency virus) is a perfect example because it uses the retrotransposition mechanism to insert itself into the genome, and then lets the host cell do the replication for it. This means that unless you kill all the cells that HIV has infected, you cant get rid of it. Thats what retrotransposons do, too. They live in the genome, including the germline so that eggs and sperm carry these genetic elements and pass them along to future generations.

Transposons have been studied quite extensively, one important impact in medicine being their role in propagating antibiotic-resistance genes in bacteria. The level of activity in an individual human body, over a single lifetime, was thought to be quite low and of minimal consequence. Its now become quite obvious thats not the full story.

First of all, its important to realize that aging is not an active process. While it might seem that youre programmed to deteriorate, aging is in fact a successive sequence of failures. Cellular processes and mechanisms become more error-prone over time. Cancer, for example, is a disease of aging because at some point, a fatal error is committed which then propagates and leads to disease. As biologists who study aging, we applied the error and failure theory to retrotransposable elements and discovered thats exactly what was happening. Its now widely appreciated that over a lifespan, these elements become more active in somatic tissues theres very good evidence that this is happening. There are multiple surveillance mechanisms that our cells use to keep these elements under control and suppress their activity; several layers of active defense that are necessary to keep the retrotransposons under wraps, so to speak. It appears that aging, or senescent, cells lose some of their ability to control the activity of retrotransposons. The defense mechanisms no longer work as well.

The aging brain of a person with Alzheimer's already shows a significant amount of damage. There's also reasonably good evidence that the brain, for some reason, is a particularly permissive site for retrotransposon activity, so the retrotransposons can basically have a field day in that tissue because theres very little that can stop them. So they promote further damage. This is a major topic in our recent review article in Nature. The question becomes: What can be done to limit the activity of these elements?

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In RA, new molecular signature test confirms who won’t respond to anti-TNF therapy during any point in therapeutic journey – BioPharma Dive

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Multiple classes of drugs exist for treating rheumatoid arthritis (RA) patients. But close to 90% of patients failing methotrexate are prescribed the worlds largest selling drug class, tumor necrosis factor- inhibitor (TNFi) therapies even though the majority dont respond adequately.

A new study published in Rheumatologyand Therapy demonstrates that PrismRA, a molecular signature test using a simple tube of blood, can predict the likelihood of not achieving a clinically meaningful response of at least a 50% improvement in symptoms in targeted therapy-nave patients and now, those patients already exposed to the TNF-inhibitor class or currently on an anti-TNF agent.

Erin Connolly-Strong, PhD, Head of Medical Affairs at Scipher Medicine, co-author of the study explains the results and science behind PrismRA.

The objective was to prospectively demonstrate that PrismRA can predict the likelihood of not achieving response, low disease activity, or remission with TNFi therapy across multiple clinical outcome measures at 3 and 6 months, including ACR50, ACR70, DAS28-CRP, and CDAI.

This was a prospective multi-center trial, which is important when we think about the objectives around the study, since a main goal was predicting the likelihood of not achieving response to the TNF-inhibitor class of medications, which are commonly prescribed for RA. We wanted to do that prospectively, but also challenge ourselves by looking at multiple disease activity measures. Our previous study had been retrospective, and we defined treatment response primarily with the ACR50 measure.

In this new study we really wanted to push the envelope, so the results could be very actionable for physicians. We demonstrated that by using the standard clinical measures, we can predict response accurately at 3 and 6 months.

Our previous study validated the PrismRA molecular signature in samples from the CorEvitas registrys CERTAIN study cohort. In this earlier study we prospectively collected both the patients molecular and clinical data.

One of the positive things about RA therapeutics is choice. There are multiple classes of drugs approved for the disease. But the American College of Rheumatology (ACR) guidelines can be a challenge when it comes to selecting targeted therapy, since the professional society doesnt rank one therapy over another or suggest an ideal prescribing order.

The dilemma for physicians is having to work through that, as well as the challenge of formularies. So, really when we think about a major problem that needs solving in RA, its that despite having all of these choices, anti-TNF therapy is the go-to.

Two out of 3 targeted treatment-nave patients will also not have an adequate response to anti-TNF medications. We need to get patients to the right therapy as quickly as possible, so that they can start to experience symptom improvement, a better quality of life, and hopefully remission.

The big question is who should not get TNF inhibitor therapy? Thats why we designed a molecular signature response classifier to rule out anti-TNF agents for those patients who are unlikely to respond to them so they can go on an alternative FDA-approved therapy faster and avoid unnecessary delays, dose escalations, or cycling.

Examining the problem more closely, there are 2 main types of patients for whom PrismRA can help inform treatment decisions first, the targeted therapy-nave patient and then second, all of the other patients who have already been exposed to the TNF-inhibitor class or are currently on an anti-TNF agent.

Providers need to know if TNF is the right pathway, as well, so thats part of what we were looking to solve in this trial to expand our intended use beyond just that nave population, but also to really be able to provide accurate predictions in that targeted therapy population as a whole.

This is one of the most fascinating areas of our research. When you go to scientific meetings, theres always a new biomarker being presented, but they rarely come to fruition. Thats because identifying individual biomarkers often doesnt consider a patients full biology, since theyre usually just a genomic or protein marker.

Were unique in that we have what we call our "molecular signature."We find a set of biological markers that capture individuals genetic makeups and their disease behavior. The molecular signature does this by including RNA, protein, and other features that reflect a patients biology.

For PrismRA specifically we include protein expression, RNA expression, patient and provider-reported outcomes, and patient characteristics. So, its all of those things together that give us the complete biology of that patient. That signature has components that are important in RA and that help us predict the patients likely response to anti-TNF treatment.

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PRECEDE Consortium Announces Konica Minolta Precision Medicine as its Precision Health Partner to Advance its Mission to Increase Survival Rates for…

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The partnership brings an integrated diagnostic approach to advance the early detection of pancreatic cancer.

ALISO VIEJO, Calif., Aug. 17, 2021 /PRNewswire/ -- The PRECEDE Consortium (PRECEDE) and Konica Minolta Precision Medicine, Inc. (KMPM) announced today that KMPM and its subsidiaries, Ambry Genetics and Invicro, have joined as partners to bring a novel integrated diagnostic approach to support PRECEDE's mission for increasing survival rates for pancreatic cancer patients through early detection.

According to the American Cancer Society, pancreatic cancer is one of the deadliest cancers, with a 5-year survival rate of just 10 percent[1]. The PRECEDE Consortium is a highly collaborative international effort comprised of over 35 leading academic medical centers across the globe to transform the early detection and prevention of pancreatic cancer, with the aim of increasing the 5-year survival rate from 10 percent to 50 percent within the next 10 years.

Together, KMPM and PRECEDE Consortium will bring their expertise and resources in genetic testing, pathology, and imaging to determine who is at an elevated risk for developing pancreatic cancer, define that risk, and invite those at elevated risk into state-of-the art clinical screening programs. The coordinated plan by KMPM and the PRECEDE Consortium is to analyze and standardize data curated through LATTICE, an integrated diagnostics platform, that runs on Amazon Web Services, Inc. (AWS). LATTICE uses Amazon HealthLake, a HIPAA-eligible service that helps organizations store, transform, query, and analyze health data, and will help researchers and clinicians gain new genomic insights for detecting and preventing pancreatic cancer.

One of the most significant challenges in determining who is at an elevated risk for pancreatic cancer has been the lack of infrastructure and protocols to support the translation of molecular imaging data, sequencing data, and diagnostics technology data. The analysis of this data is critical for informing disease detection, prevention, and treatment. KMPM's focus on multi-omics and multimodal data has spurred their development of LATTICE, which they plan to use to securely aggregate diagnostics, imaging, and informatics data from the PRECEDE study in one seamless, standardized platform to better derive new insights for preventive and managed care.

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"As a surgeon and scientist who has spent my entire career taking care of pancreatic cancer patients and trying to improve survival for this intractable disease, it is clear that early detection is likely to have the greatest impact in changing outcomes," said Dr. Diane M. Simeone, Principal Investigator of PRECEDE and Director of the Pancreatic Cancer Center at NYU Langone Health. "Through this innovative partnership we expect to curate and analyze large amounts of data in an unprecedented way to optimize early detection methods for pancreatic cancer."

"Machine learning may offer healthcare and life sciences organizations the opportunity to normalize, index, structure, and aggregate data in a way that makes it easier for clinicians to understand relationships in data and support better patient care," said Dr. Taha Kass Hout, Director of Machine Learning at AWS. "We are excited to support the PRECEDE Consortium as they work to predict and prevent pancreatic cancer using LATTICE."

"Early identification can have a life-changing impact for patients at a high risk for pancreatic cancer," said Aaron Elliott, KMPM CEO. "By leveraging the LATTICE platform, PRECEDE will be able to help more healthcare providers, researchers, and scientists harness the power of diagnostics, imaging, and informatics to find novel associations and biomarkers for the early detection of pancreatic cancer."

The PRECEDE Consortium is currently providing clinical care to high-risk patients at designated academic medical institutions and enrolling eligible patients into its observational longitudinal prospective cohort study. The PRECEDE study plans to grow to include over a hundred institutional partnerships and expand the cohort to over 10,000 high risk individuals for this important study. For more information on PRECEDE and its Consortium members please visit, precedestudy.org

About PRECEDE Founded in 2018, The PRECEDE Consortium is a highly collaborative international effort to improve survival for pancreatic cancer by improving early detection, screening, risk modeling, and prevention for those with a heritable risk for pancreatic cancer. PRECEDE's mission is to increase the survival of patients diagnosed with pancreatic cancer from 10% to 50% in the next ten years by partnering with top researchers, industry, academic institutions, survivors, and families dedicated to preventing and ending pancreatic cancer. The largest effort of its kind, PRECEDE utilizes a novel collaboration and data-sharing model to evaluate at-risk individuals for pancreatic cancer. Working collaboratively, PRECEDE aims to better define who is at risk, determine the level of risk, and enroll those at elevated risk into state-of-the-art screening programs to help put an end to pancreatic cancer.

About KONICA MINOLTA PRECISION MEDICINE, Inc.Konica Minolta Precision Medicine, Inc. (KMPM) is a comprehensive precision diagnostics company dedicated to advancing technologies that accurately predict, detect and treat disease. Powered by proprietary software platforms, best-in-class genomics technology from Ambry Genetics Corporation, and industry-leading radiology and pathology services from Invicro, LLC, KMPM is uniquely equipped to collect, analyze, and report on multi-modal precision diagnostic data sets. This comprehensive approach will drive clinical access to novel diagnostic assays through the company's extensive network of healthcare providers and pharmaceutical partners. LATTICE is a trademark of Ambry Genetics.

Media Contact:Simone Jackenthal Email: sjackenthal@tridentdmg.com

[1] American Cancer Society. Cancer Facts & Figures 2021. Atlanta, Ga: American Cancer Society; 2021.

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