Culture

The structure of organic substances tetrahydroisoquinolines (THIQ) includes a benzene ring fused with a nitrogen-containing cycle. These compounds are in high demand in the pharmaceutical industry. They are used in the synthesis of myorelaxants, antidepressants, and drugs against hypertension, cough, and insomnia. Although different variations of THIQ structures can be found in natural sources (for example, as parts of phytotoxins), modern-day pharmaceutical manufacturers are also interested in their rare types, such as spirocyclic THIQs. In their molecules, two adjacent cycles share one common atom, thus creating an unusual and very stable 3D structure. This feature is extremely important for drug design: the more stable a molecule's spatial structure is, the more accurately it can be aimed at a protein target in a body.

The majority of existing approaches to the synthesis of spirocyclic THIQs are quite time-consuming. They involve complex cycle-forming reactions arranged in a linear sequence. A team of chemists from Immanuel Kant Baltic Federal University and Saint Petersburg State University found a way to reduce this process to just three steps and to combine the first two into one chemical operation.

The first step is the so-called Castagnoli-Cushman reaction. Earlier this year the BFU-SPbSU team had reported a new version of this reaction in which the product (various carboxylic acids) is formed from three components: homophthalic anhydride (an organic substance with a benzene ring fused to an oxygen cycle with two carbonyl groups), cyclic ketones, and ammonium acetate that works as a source of nitrogen. The team tested the new THIQ synthesis method using cyclohexanone as a ketone. After 16 hours of reaction, a carboxylic acid was formed from the reagents. The acid contained three rings, two of which already shared a common atom. The next steps were focused on removing the waste products of the reaction while preserving the spirocyclic compound intact. First of all, the team heated the compound in dimethyl sulfoxide to remove the -COOH carboxylic group. This step did not require any purification of the first reaction products. As a result, the acid turned into THIQ lactam, a substance that only differs from the target reaction product by one extra oxygen atom. A reduction reaction of the lactam with lithium aluminum hydride completed the process.

All stages of the process proceeded in high yield: 79% of the initial homophthalic anhydride turned into THIQ lactam, and 78% of lactam produced spirocyclic THIQ. Having confirmed the efficiency of the new method, the team carried out the same series of reactions using other cyclic ketones. Of the 14 tested options, the majority also showed a high THIQ yield. Therefore, the new method can be used to obtain substances with various structures.

"We have developed an effective approach to the synthesis of spirocyclic tetrahydroisoquinolines that is also much easier compared to existing procedures. It can increase our opportunities for the development of THIQ-based compounds for the pharmaceutical industry. Moreover, the same approach can be applied to other compounds that might serve as prototypes for new drugs", said Mikhail Krasavin, D.Sc. in Chemistry, Research Professor at the Institute of Living Systems (BFU), and the Head of the Department of the Chemistry of Natural Products (SPbSU).

The term "algae" is used to refer to over 72,500 identified aquatic species. The size of algae is up to tens of meters, however, most (about 80%) of the species are much smaller - they comprise the microalgae group. Microalgae are rich in nutrients and biologically active substances such as proteins, carbohydrates, lipids, vitamins, pigments and others. These components are widely used in food, cosmetic, chemical and energy industries. Biotechnology of microalgae has multiple advantages: they are a renewable and sustainable resource, more productive than terrestrial plants due to their high growth rate and lack of seasonality of cultivation, and also less sensitive to environmental conditions.

Nowadays there is a growing practical interest in the lipids and fatty acids from microalgae. At the moment, there are a limited number of species from which lipids can be obtained in good yield; the oil content in the most promising of them is about 20-50% calculated on dry matter. Fatty acids are composed of carbon, hydrogen and oxygen atoms. Depending on the bonds between carbon atoms, they are classified into two groups - saturated (all bonds are single) and unsaturated (there is at least one double bond). Polyunsaturated fatty acids - the famous Ω-6 and Ω-3 families - are especially useful for human health. They cannot be formed in the body and must be supplied with food; a balanced diet with the correct polyunsaturated fatty acids amount reduces the risk of heart and vascular diseases, arthritis and depression.

Microalgae are an important source of fatty acids: most of them accumulate saturated palmitic and monounsaturated oleic acids, but, for example, spirulina is a reservoir for linoleic and γ-linolenic acids (Ω-6). Moreover, the fatty acid profile can vary for the same species depending on the cultivation conditions and the composition of the nutrient medium. In the nearest future polyunsaturated fatty acids from microalgae will play a significant role in the industrial sector due to their biological activity and positive effects on human health.

The work of Russian scientists was aimed at studying the qualitative and quantitative composition of fatty acids of microalgae typical for water bodies (Lake Vištytis, Lake Chaika, Lake Yantarnoye, Curonian Lagoon, Strait of Baltiysk, Baltic Sea coast, Lake Krasnoye) of the Kaliningrad region. The authors took samples of water and soil, cultivated the microorganisms from the probes on a nutrient medium and sequenced them for the accurate identification of the species. After that, the optimal conditions for the cultivation of microalgae in terms of maximal lipids accumulation were chosen. The cells were centrifuged then, the cell walls were destroyed and lipids were separated from the resulting mass. The composition of fatty acids was determined using high performance liquid chromatography - a separation method based on the different distribution of substances between two immiscible phases, in which the liquid, the mobile phase, moves with high hydraulic resistance.

It turned out that the most saturated fatty acids were characteristic of the microalgae Chlorella vulgaris and Dunaliella salina. In the Dunaliella salina and Arthrospira platensis, the maximum degree of unsaturated fatty acids ranged from 15 to 23%. Lipid complex of microalgae included neutral lipids, polar lipids, unsaponifiable substances and other impurities. Thus, these organisms represent a promising route for practical implementation.

"Studies have shown that microalgal biomass is a prospective product as it is a great new source of lipids. The possibility of their use for the production of dietary supplements for humans and feed additives for animals is encouraging. Despite the potential of this idea, there are still technologies that have to be developed for the reduction of the cost of lipids from microalgae," says Olga Babich, Director of the Institute of Living Systems of the Immanuel Kant Baltic Federal University, Doctor of Technical Sciences.

Individually, California blackworms live an unremarkable life eating microorganisms in ponds and serving as tropical fish food for aquarium enthusiasts. But together, tens, hundreds, or thousands of the centimeter-long creatures can collaborate to form a "worm blob," a shape-shifting living liquid that collectively protects its members from drying out and helps them escape threats such as excessive heat.

While other organisms form collective flocks, schools, or swarms for such purposes as mating, predation, and protection, the Lumbriculus variegatus worms are unusual in their ability to braid themselves together to accomplish tasks that unconnected individuals cannot. A new study reported by researchers at the Georgia Institute of Technology describes how the worms self-organize to act as entangled "active matter," creating surprising collective behaviors whose principles have been applied to help blobs of simple robots evolve their own locomotion.

The research, supported by the National Science Foundation and the Army Research Office, was reported Feb. 5 in the journal Proceedings of the National Academy of Sciences. Findings from the work could help developers of swarm robots understand how emergent behavior of entangled active matter can produce unexpected, complex, and potentially useful mechanically driven behaviors.

Collective Behavior in Worms

The spark for the research came several years ago in California, where Saad Bhamla was intrigued by blobs of the worms he saw in a backyard pond.

"We were curious about why these worms would form these living blobs," said Bhamla, an assistant professor in Georgia Tech's School of Chemical and Biomolecular Engineering. "We have now shown through mathematical models and biological experiments that forming the blobs confers a kind of collective decision-making that enables worms in a larger blob to survive longer against desiccation. We also showed that they can move together, a collective behavior that's not done by any other organisms we know of at the macro scale."

Such collective behavior in living systems is of interest to researchers exploring ways to apply the principles of living systems to human-designed systems such as swarm robots, in which individuals must also work together to create complex behaviors.

"The worm blob collective turns out to have capabilities that are more than what the individuals have, a wonderful example of biological emergence," said Daniel Goldman, a Dunn Family Professor in Georgia Tech's School of Physics, who studies the physics of living systems.

Why the Worms Form Blobs

The worm blob system was studied extensively by Yasemin Ozkan-Aydin, a research associate in Goldman's lab. Using bundles of worms she originally ordered from a California aquarium supply company - and now raises in Georgia Tech labs - Ozkan-Aydin put the worms through several experiments. Those included development of a "worm gymnasium" that allowed her to measure the strength of individual worms, knowledge important to understanding how small numbers of the creatures can move an entire blob.

She started by taking the aquatic worms out of the water and watching their behavior. First, they individually began searching for water. When that search failed, they formed a ball-shaped blob in which individuals took turns on the outer surface exposed to the air where evaporation was taking place - behavior she theorized would reduce the effect of evaporation on the collective. By studying the blobs, she learned that worms in a blob could survive out of water 10 times longer than individual worms could.

"They would certainly want to reduce desiccation, but the way in which they would do this is not obvious and points to a kind of collective intelligence in the system," said Goldman. "They are not just surface-minimizing machines. They are looking to exploit good conditions and resources."

Using Blobs to Escape Threats

Ozkan-Aydin also studied how worm blobs responded to both temperature gradients and intense light. The worms need a specific range of temperatures to survive and dislike intense light. When a blob was placed on a heated plate, it slowly moved away from the hotter portion of the plate to the cooler portion and under intense light formed tightly entangled blobs. The worms appeared to divide responsibilities for the movement, with some individuals pulling the blob while others helped lift the aggregation to reduce friction.

As with evaporation, the collective activity improves the chances of survival for the entire group, which can range from 10 worms up to as many as 50,000.

"For an individual worm going from hot to cold, survival depends on chance," said Bhamla. "When they move as a blob, they move more slowly because they have to coordinate the mechanics. But if they move as a blob, 95% of them get to the cold side, so being part of the blob confers many survival advantages."

A Worm Gymnasium

The researchers noted that only two or three "puller" worms were needed to drag a 15-worm blob. That led them to wonder just how strong the creatures were, so Ozkan-Aydin created a series of poles and cantilevers in which she could measure the forces exerted by individual worms. This "worm gymnasium" allowed her to appreciate how the pullers managed to do their jobs.

"When the worms are happy and cool, they stretch out and grab onto one of the poles with their heads and they pull onto it," Bhamla said. "When they are pulling, you can see the deflection of the cantilever to which their tails were attached. Yasemin was able to use known weights to calibrate the forces the worms create. The force measurement shows the individual worms are packing a lot of power."

Some worms were stronger than others, and as the temperature increased, their willingness to work out at the gym declined.

Applying Worm Principles to Robots

Ozkan-Aydin also applied the principles observed in the worms to small robotic blobs composed of "smart active particles," six 3D-printed robots with two arms and two sensors allowing them to sense light. She added a mesh enclosure and pins to arms that allowed these "smarticles" to be entangled like the worms and tested a variety of gaits and movements that could be programmed into them.

"Depending on the intensity, the robots try to move away from the light," Ozkan-Aydin said. "They generate emergent behavior that is similar to what we saw in the worms."

She noted that there was no communication among the robots. "Each robot is doing its own thing in a decentralized way," she said. "Using just the mechanical interaction and the attraction each robot had for light intensity, we could control the robot blob."

By measuring the energy consumption of an individual robot when it performed different gaits (wiggle and crawl), she determined that the wiggle gait uses less power than the crawl gait. The researchers anticipate that by exploiting gait differentiation, future entangled robotic swarms could improve their energy efficiency.

Expanding What Robot Swarms Can Do

The researchers hope to continue their study of the collective dynamics of the worm blobs and apply what they learn to swarm robots, which must work together with little communication to accomplish tasks that they could not do alone. But those systems must be able to work in the real world.

"Often people want to make robot swarms do specific things, but they tend to be operating in pristine environments with simple situations," said Goldman. "With these blobs, the whole point is that they work only because of physical interaction among the individuals. That's an interesting factor to bring into robotics."

Among the challenges ahead are recruiting graduate students willing to work with the worm blobs, which have the consistency of bread dough.

"The worms are very nice to work with," said Ozkan-Aydin. "We can play with them and they are very friendly. But it takes a person who is very comfortable working with living systems."

The project shows how the biological world can provide insights beneficial to the field of robotics, said Kathryn Dickson, program director of the Physiological Mechanisms and Biomechanics Program at the National Science Foundation.

"This discovery shows that observations of animal behavior in natural settings, along with biological experiments and modeling, can offer new insights, and how new knowledge gained from interdisciplinary research can help humans, for example, in the robotic control applications arising from this work," she said.

HOUSTON - (Feb. 9, 2021) - Finding a needle in a haystack is hard enough. But try finding a specific molecule on the needle.

Rice University researchers have achieved something of the sort with a new genome editing tool that targets the supporting players in a cell's nucleus that package DNA and aid gene expression. Their work opens the door to new therapies for cancer and other diseases.

Rice bioengineer Isaac Hilton, postdoctoral researcher and lead author Jing Li and their colleagues programmed a modified CRISPR/Cas9 complex to target specific histones, ubiquitous epigenetic proteins that keep DNA in order, with pinpoint accuracy.

The open-access research appears in Nature Communications.

Histones help regulate many cellular processes. There are four in each nucleosome (the basic "beads on a string" in DNA) that help control the structure and function of our genomes by exposing genes for activation.

"Nucleosomes serve as architectural substrates to fit our DNA inside of our cells, and can also control access to key parts of our genomes," Hilton said.

Like other proteins, histones can be triggered by phosphorylation, the addition of a phosphoryl group that can control protein-protein or protein-DNA interactions.

"Histones can display an exquisitely diverse spectrum of chemical modifications that serve as beacons or regulatory markers and tell which genes to turn on, and when, and how much to do so," Hilton said. "One of these mysterious modifications is phosphorylation, and we aimed to better illuminate the mechanism by which it can rapidly turn human genes on and off."

No other epigenome editing technique has enabled site-specific control over histone phosphorylation, he said. The programmable Rice tool, called dCas9-dMSK1, fuses a deactivated "dCas9" protein and a "hyperactive" human histone kinase, an enzyme that catalyzes phosphorylation.

CRISPR/Cas9 typically employs guide RNAs and Cas9 "scissors" to target and cut sequences in DNA. The new tool programs deactivated dCas9 to target without cutting sequences, instead using the recruited dMSK1 enzyme to phosphorylate the targeted histone and turn on nearby genes.

The researchers used dCas9-dMSK1 to uncover novel genes and pathways that are pivotal for drug resistance. Li used it to identify three genes previously linked to melanoma drug resistance. "And then she identified seven new genes linked to melanoma resistance," Hilton said. "It's an exciting finding that we are following up on.

"Histone proteins that wrap up DNA can have all sorts of chemical marks and combinations on them," he said. "This results in what has been dubbed a histone code, and one of our goals is to work to decipher it."

Li's tool also confirms how specific histone marks communicate with one another. "It tells us that chemical modifications on histones talk to each other, and we can show it happening at specific spots in the human genome," Li said. "And that's linked to a gene turning on, so this allows us to synthetically control them."

Li said a long-term goal is to target a range of other histone marks. "It's a complicated story," she said. "There are a lot of different positions and features of histones that we want to study."

"Getting these technologies into patients is a long process," Hilton added. "But tools like this are the first step and can pave the way towards understanding how normal cellular processes unfortunately go awry in human diseases."

RIVERSIDE, Calif. -- A team led by astronomers at the University of California, Riverside, has found that some dwarf galaxies may today appear to be dark-matter free even though they formed as galaxies dominated by dark matter in the past.

Galaxies that appear to have little to no dark matter -- nonluminous material thought to constitute 85% of matter in the universe -- complicate astronomers' understanding of the universe's dark matter content. Such galaxies, which have recently been found in observations, challenge a cosmological model used by astronomers called Lambda Cold Dark Matter, or LCDM, where all galaxies are surrounded by a massive and extended dark matter halo.

Dark-matter-free galaxies are not well understood in the astronomical community. One way to study the possible formation mechanisms for these elusive galaxies -- the ultradiffuse DF2 and DF4 galaxies are examples -- is to find similar objects in numerical simulations and study their time evolution and the circumstances that lead to their dark matter loss.

Jessica Doppel, a graduate student in the UC Riverside Department of Physics and Astronomy and the first author of research paper published in the Monthly Notices of the Royal Astronomical Society, explained that in a LCDM universe all galaxies should be dark matter dominated.

"That's the challenge," she said. "Finding analogs in simulations of what observers see is significant and not guaranteed. Beginning to pin down the origins of these types of objects and their often-anomalous globular cluster populations allows us to further solidify our theoretical framework of dark matter and galaxy formation and confirms that no alternative forms of dark matter are needed. We found cold dark matter performs well."

For the study, the researchers used cosmological and hydrodynamical simulation called Illustris, which offers a galaxy formation model that includes stellar evolution, supernova feedback, black hole growth, and mergers. The researchers found a couple of "dwarf galaxies" in clusters had similar stellar content, globular cluster numbers, and dark matter mass as DF2 and DF4. As its name suggests, a dwarf galaxy is small, comprising up to several billion stars. In contrast, the Milky Way, which has more than 20 known dwarf galaxies orbiting it, has 200 to 400 billion stars. Globular clusters are often used to estimate the dark matter content of galaxies, especially dwarfs.

The researchers used the Illustris simulation to investigate the origin of odd dwarf galaxies such as DF2 and DF4. They found simulated analogs to dark-matter-free dwarfs in the form of objects that had evolved within the galaxy clusters for a long time and lost more than 90% of their dark matter via tidal stripping -- the stripping away of material by galactic tidal forces.

"Interestingly, the same mechanism of tidal stripping is able to explain other properties of dwarfs like DF2 and DF4 -- for example, the fact that they are 'ultradiffuse' galaxies," said co-author Laura Sales, an associate professor of physics and astronomy at UCR and Doppel's graduate advisor. "Our simulations suggest a combined solution to both the structure of these dwarfs and their low dark matter content. Possibly, extreme tidal mass loss in otherwise normal dwarf galaxies is how ultradiffuse objects are formed."

In collaboration with researchers at the Max Planck Institute for Astrophysics in Germany, Sales' group is currently working with improved simulations that feature more detailed physics and a numerical resolution about 16 times better than the Illustris simulation.

"With these data, we will be able to extend our study to even lower-mass dwarfs, which are more abundant in the universe and expected to be more dark matter dominated at their centers, making them more challenging to explain," Doppel said. "We will explore if tidal stripping could provide a path to deplete dwarfs of their inner dark matter content. We plan to make predictions about the dwarfs' stellar, globular cluster, and dark matter content, which we will then compare to future observations."

EXPERTS SAY STANDARDIZED DATA ARE NEEDED TO EFFECTIVELY MANAGE THE COVID-19 PANDEMIC

Media Contact: Marisol Martinez, mmart150@jhmi.edu

In the age of COVID-19, decisions that affect our day-to-day lives are influenced by analyzing numbers and data. For example, the COVID-19 positivity rate (the percentage of people who test positive for the virus out of the total number tested) influence whether or not businesses may open to the public, or, if schools should offer virtual, hybrid or in-class learning. Data are critical for strategizing, planning and implementing the policies and procedures needed to respond to the crisis and keep people safe. But what happens if different organizations are using different definitions to track the same data? Now, in a commentary published online Dec. 23, 2020, in the Journal of Hospital Medicine, J. Matthew Austin, Ph.D., M.S., and Allen Kachalia, M.D., J.D., highlight how the lack of standardized definitions for many key measures needed to manage the public health response can lead to debate, confusion and politicization of pandemic data.

During the early stages of the pandemic, Austin and Kachalia, at the Johns Hopkins Armstrong Institute for Patient Safety and Quality, began to question the methods used to report the number of positive COVID-19 cases in Maryland, as cases were being reported publically by the day the test result was known -- not by the day the test was conducted. In turn, this got them thinking about how the decisions that were being made regarding how to collect and report these data could have a serious impact on how people work and live.

"This is not about a right way or a wrong way of collecting these data," says Austin, a faculty member at the Armstrong Institute and assistant professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine. "What we're advocating is a standardized way of collecting and analyzing data so that we can effectively manage this pandemic and future ones."

In their commentary, Austin and Kachalia propose, among other recommendations, that health care officials in the United States create a consensus task force to identify and define metrics and, over time, refine them -- based on the prevailing science and public health priorities. They believe that once metrics are standardized, public health leaders and health care organizations will be able to use the improvements in performance and outcomes to identify which strategies are best suited for future public health planning and actions.

MISSED MEDICATIONS AREN'T REASON FOR GREATER RISK OF CLOTS IN PATIENTS WITH COVID-19

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

According to recent research studies, patients hospitalized with COVID-19 are at high risk of developing venous thromboembolism (VTE), a potentially deadly condition in which a blood clot forms in the deep veins of the leg, groin or arm (known as a deep vein thrombosis, or DVT) and may dislodge. If that happens, the clot can travel via the bloodstream to lodge in the lungs and cause tissue damage or death from reduced oxygen (known as a pulmonary embolism, or PE). It has recently been thought that missed doses of anti-clotting drugs in patients with COVID-19 in hospital settings might contribute to increased rates of hospital-associated VTEs.

Now, a Johns Hopkins Medicine research team has provided evidence that the high hospital-associated VTE incident rate among patients with COVID-19 is not due to clot-preventing medications -- primarily anticoagulants (commonly called "blood thinners") -- being missed or not prescribed at all during treatment, as previously suspected.
The findings were reported online Jan. 28, 2021, in the Journal of Thrombosis and Thrombolysis.

In their retrospective study, the researchers looked at medical records for all 5,790 adult patients discharged from The Johns Hopkins Hospital between March 1 and May 12, 2020 -- including those who tested positively (439) or negatively (2,316) for COVID-19, or weren't tested at all (3,035). They compared the three groups for demographics, clinical characteristics, VTE outcomes, and the prescription and administration of VTE-preventive medications.

"While nonadministration of VTE prophylaxis in hospitals is known to be common, it wasn't the case for the patients with COVID-19 that we studied," says Elliott Haut, M.D., Ph.D., associate professor of surgery at the Johns Hopkins University School of Medicine and senior author of the study. "In fact, patients with COVID-19 were more frequently administered all doses of the preventive medications prescribed for them."

Haut says that the team suspects this finding reflects enhanced vigilance and prioritization by physicians (for prescribing) and nurses (for administering), due to the evidence that patients with COVID-19 have a higher risk for VTEs.

"Awareness of the high VTE risk in patients with COVID-19 has resulted in better administration of pharmacologic prophylaxis for these patients," says Mujan Varasteh Kia, M.P.H., a research assistant at the Johns Hopkins University School of Medicine and study lead author.

Before the study, Haut says the research team hypothesized that decreased patient contact and limited supplies of personal protective equipment during the early stages of the COVID-19 pandemic might have hindered the administration of VTE prophylaxis in patients with the disease. Had the study shown that to be true, Haut explains, educating health care staff to avoid missing doses would have been a relatively simple solution.

"However, we actually learned from our study that doctors and nurses are probably doing a good job of trying to prevent VTEs in patients with COVID-19 through drug intervention," Haut says. "We believe therefore, that future research efforts should prioritize finding and implementing alternative approaches to optimizing VTE prevention in these patients."

Haut and Varasteh Kia are available for interviews.

ORGAN TRANSPLANT RECIPIENTS CAN DEVELOP IMMUNITY AFTER COVID-19, DESPITE IMMUNOSUPPRESSION

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

Johns Hopkins Medicine researchers have shown that it is possible for solid organ transplant recipients who contract COVID-19 to experience a natural immune response to SARS-CoV-2, the virus that causes the disease. In their study, published online Jan. 19, 2021, in the journal Transplantation, the researchers also suggest that measures used to provide short-term immunity against SARS-CoV-2 -- such as convalescent plasma (which contains antibodies from patients who have recovered from COVID-19) -- may actually reduce the natural response.

"We followed 18 transplant recipients who were taking immunosuppressive medications to prevent rejection and who developed COVID-19 post-transplant," says study co-author Dorry Segev, M.D., Ph.D., the Marjory K. and Thomas Pozefsky Professor of Surgery and Epidemiology and director of the Epidemiology Research Group in Organ Transplantation at the Johns Hopkins University School of Medicine. "Our goal was to gain a deeper understanding of the immune response in these individuals, so that clinicians will be better able to treat transplant recipients who get COVID-19, prevent their disease from becoming severe and develop vaccine protocols that fit their special needs."

The study participants, all of whom were receiving immunosuppressive medication, represented a variety of organ transplants: nine kidney, five liver, one kidney and liver, two lung and one composite tissue allograft (composed of different tissue types, such as skin, muscle, bone, bone marrow, lymph nodes, nerves and tendons). The median age was 56, 56% (10) were female, 33% (six) were Black and 11% (two) were Hispanic. COVID-19 occurred at a median of six years following transplant surgery, with 89% (16) experiencing symptoms and 72% (13) requiring hospitalization. Five patients received convalescent plasma during their hospital stay.
When the participants were screened for SARS-CoV-2 antibodies at a median 98 days after COVID-19 diagnosis, the researchers observed that most had antibody levels suggesting neutralizing immunity -- the ability to prevent reinfection if exposed to the virus in the future.

Transplant recipients who had more severe cases of COVID-19, the researchers say, tended to have the highest antibody levels.

Interestingly, the researchers found that transplant recipients who received convalescent plasma or intravenous immunoglobulin (to reduce the risk of a serious inflammatory response) had lower natural antibody levels against the virus and, therefore, were less likely to have immunity.

"This raises the possibility that administered antibody preparations may blunt the natural formation of antibodies against SARS-CoV-2," says Jacqueline Garonzik Wang, M.D., Ph.D., associate professor of surgery at the Johns Hopkins University School of Medicine and study senior author. "Larger studies will be needed to substantiate this finding, which, if proven, would be invaluable to COVID-19 vaccine protocol development for the immunocompromised."

Segev and Garonzik Wang are available for interviews.

STUDY INDICATES COVID-19 VACCINES ARE SAFE FOR ORGAN TRANSPLANT PATIENTS

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

In what may be the first study of its kind, Johns Hopkins Medicine researchers have documented the reaction of nearly 200 solid organ transplant recipients to their first vaccine inoculation against SARS-CoV-2, the virus that causes COVID-19. The findings, they say, provide evidence that both the Moderna and Pfizer/BioNTech messenger RNA (mRNA) vaccines can be safely given to this immunocompromised population.

The study was posted online Feb. 5, 2021, in the journal Transplantation.

To better understand the safety of the SARS-CoV-2 mRNA vaccines for transplant patients, the researchers studied 187 transplant recipients who received an initial dose of either the Moderna or Pfizer/BioNTech vaccines between Dec. 16, 2020and Jan. 16, 2021. The study participants were recruited by invitation through their transplant centers or social media.

Fifty-two percent (97) were kidney transplant recipients; 19% (35) were liver; 14% (26) were heart; 9% (17) were lung; 3% (six) were kidney and pancreas; and (six) were other multi-organ recipients. The median age was 48; 69% (129) were female, 87% (163) were white; and 6% (11) were Hispanic or Latino. Vaccinations occurred at a median of six years following transplant surgery. All were receiving immunosuppression medications to prevent rejection of their transplanted organs.

Between the time of their vaccination and study participation (which consisted of completing a detailed questionnaire one week after they received the vaccine), there were no diagnoses of SARS-CoV-2 infections.

Few of the transplant recipients in the study had systemic adverse reactions, such as fever (seven, or 4%) and chills (17, or 9%), to the Moderna and Pfizer/BioNTech vaccines -- statistics that were similar to those seen for participants in the large, randomized clinical trials that validated the safety of the two prophylactic treatments. The majority of the transplant recipients reported local reactions, including mild pain at the site of inoculation (114, or 61%), mild redness (13, or 7%) and mild swelling (30, or 16%).

Additionally, the researchers say, organ rejection -- a common concern about vaccinating transplant recipients -- did not occur.

"We hope to further this research by exploring any unexpected safety issues with long-term follow-up studies of these patients in the future," says Jacqueline Garonzik Wang, M.D., Ph.D., associate professor of surgery at the Johns Hopkins University School of Medicine and study senior author.

"These insights are critical toward protecting the lives and quelling the fears of transplant recipients who might be hesitant about getting the SARS-CoV-2 vaccines," says study co-author Dorry Segev, M.D., Ph.D., the Marjory K. and Thomas Pozefsky Professor of Surgery and Epidemiology and director of the Epidemiology Research Group in Organ Transplantation at the Johns Hopkins University School of Medicine.

Garonzik Wang and Segev are available for interviews.

ALBUQUERQUE, N.M. -- The huge forces generated by the Z machine at Sandia National Laboratories are being used to replicate the gravitational pressures on so-called "super-Earths" to determine which might maintain atmospheres that could support life.

Astronomers believe that super-Earths -- collections of rocks up to eight times larger than Earth -- exist in the millions in our galaxy. "The question before us is whether any of these super planets are actually Earthlike, with active geological processes, atmospheres and magnetic fields," said Sandia physicist Joshua Townsend.

The current work at Z is described in today's Nature Communications. Researchers in Sandia's Fundamental Science Program, working with colleagues at the Earth and Planets Laboratory of the Carnegie Institution for Science in Washington, D.C., use the forces available at Sandia's uniquely powerful Z facility to near-instantly apply the equivalent of huge gravitational pressures to bridgmanite, also known as magnesium-silicate, the most abundant material in solid planets.

The experiments, said Townsend, gave birth to a data-supported table that shows when a planet's interior would be solid, liquid or gaseous under various pressures, temperatures and densities, and in what predicted time spans. Only a liquid core -- with its metals shifting over each other in conditions resembling that of an earthly dynamo -- produces the magnetic fields that can shunt destructive solar winds and cosmic rays away from a planet's atmosphere, allowing life to survive. This critical information about magnetic field strengths produced by the core states of different-sized super-Earths was formerly unavailable: cores are well-hidden by the bulk of the planets surrounding them, and thus not visible by remote viewing. For researchers who preferred earthly experiments rather than long-distance imaging, sufficient pressures weren't available until Z's capabilities were enlisted.

Yingwei Fei, the corresponding author of the current study and senior staff scientist at Carnegie's Earth and Planets Laboratory, is known for his skill in synthesizing large-diameter bridgmanite using multiton presses with sintered diamond anvils.

"Z has provided our collaboration a unique tool that no other technique can match, for us to explore the extreme conditions of super-Earths' interiors," he said. "The machine's unprecedented high-quality data have been critical for advancing our knowledge of super-Earths."

The Magnificent Seven

Further analysis of the state of gaseous and dense materials on specific super-Earths produced a list of seven planets possibly worthy of further study: 55 Cancri e; Kepler 10b, 36b, 80e, and 93b; CoRoT-7b; and HD-219134b.

Sandia manager Christopher Seagle, who with Fei initially proposed these experiments, said, "These planets, which we found most likely to support life, were selected for further study because they have similar ratios to Earth in their iron, silicates and volatile gasses, in addition to interior temperatures conducive to maintaining magnetic fields for protection against solar wind."

The focus on supersized, rather than small, planets came about because large gravitational pressures mean atmospheres are more likely to survive over the long haul, said Townsend.

For example, he said, "Because Mars was smaller, it had a weaker gravitational field to begin with. Then as its core quickly cooled, it lost its magnetic field and its atmosphere was subsequently stripped away."

Z in action

For these experiments, the Z machine, with operating conditions of up to 26 million amps and hundreds of thousands of volts, creates magnetic pulses of enormous power that accelerate credit card-sized pieces of copper and aluminum called flyer-plates. These were propelled much faster than a rifle bullet into samples of bridgmanite, the Earth's most common mineral. The near-instantaneous pressure of the forceful interaction created longitudinal and transverse sound waves in the material that reveal whether the material remains solid or changes to a liquid or gas, said Sandia researcher and paper author Chad McCoy. With these new results, researchers were supplied with solid data on which to anchor otherwise theoretical planetary models.

The technical paper concludes that the high-precision density data and unprecedently high melting temperatures achieved at the Z machine "provide benchmarks for theoretical calculations under extreme conditions."

Concluded Fei, "Our collaboration with Sandia scientists has led to results that will encourage more academic exploration of exoplanets, whose discovery has captured the public imagination."

"This work identifies interesting exoplanet candidates to explore further," said Seagle. "Z shock compression plus Fei's unusual capability to synthesize large-diameter bridgmanite lead to an opportunity to obtain data relevant to exoplanets that would not be possible anywhere else."

The notion of social distancing rose to public prominence approximately a year ago, when health officials began recommending it as a way to slow the spread of the novel SARS-CoV-2 virus. Despite the novelty of the concept among many contemporary human audiences, social distancing has considerable precedent among animals.
Writing in BioScience, Mark Butler of Florida International University and Donald C. Behringer of the University of Florida outline the role of social distancing in nature and compare it with its human counterpart. They describe numerous animals in which distancing has evolved, including guppies, chimpanzees, birds, ants, and mice, among many others.

Often, say the authors, social distancing can mark substantial behavioral changes in otherwise highly social species. Butler and Behringer describe the seasonal migrations of spiny lobsters, which occur "en masse, strung out on the seafloor in dramatic single-file lines or queues." However, because juveniles are particularly susceptible to a virus known as PaV1, which can kill 90% of those infected, healthy lobsters detect and refuse to shelter alongside their diseased conspecifics.

Similarly, say the authors, chimpanzees are known to ostracize unwell group members, such as those infected with polio, and are also thought to benefit from a general avoidance of individuals outside their immediate group. Further examples abound, including among highly social house finches, which avoid experimentally sickened members of the same species, and three-spined stickleback fish, which avoid schools that contain ectoparasite-infected individuals. Some animals even deploy other strategies that resemble humans' disease precautions, such as ants that "use poisons to disinfect their colonies and prevent epizootics."

According to the authors, a key to animals' successful deployment of social distancing lies in their ability to effectively use cues--often olfactory--to detect sickened individuals. Indeed, animals are often able to "use social distancing effectively and efficiently." In contrast, humans are typically forced to rely on low-accuracy visual or auditory cues, such as feverish appearance or coughing, highlighting the importance of diagnostic testing for the effective reduction of disease transmission.

Butler and Behringer suggest that future study may further illuminate and inform human responses to disease: "The examples of social distancing in wild animals in the present article, although they are compelling, are likely a small fraction of those that actually exist in nature and reflect the limited investigations conducted thus far on this phenomenon in the wild. What lessons might we learn about the human experience with pandemics from an expanded view of diseases, their spread, and their prevention in nature?"

New research by Morgan Philbin, PhD, at Columbia University Mailman School of Public Health and colleagues looks at why Black young men who have sex with men (YMSM) are disproportionately subject to high rates of arrest and incarceration. They find that perceived racial discrimination, sexual orientation discrimination, and HIV-status discrimination are all associated with risk for criminal justice involvement in this population.

The research appears in the journal Stigma and Health.

Various studies have shown that Black men are imprisoned at nearly seven times the rate of white men; sexual minority young adults are nearly three times more likely to report being criminally sanctioned compared to their heterosexual peers; and the rate of HIV among prisoners is multiple times higher than the general population. Discrimination can occur at all stages of criminal justice involvement, from differential enforcement and/or threats of violence by police officers to court proceedings and sentencings.

The longitudinal study of 465 Black YMSM at risk for HIV in North Carolina explored discrimination at baseline and finds that perceived racism was the strongest predictor of subsequent criminal justice involvement (29 percent increased odds) followed by perceptions of sexual orientation discrimination (12 percent increased odds) and HIV discrimination (6 percent increased odds).

Unlike most research on predictors of criminal justice involvement that focus on individual-level factors such as race, homelessness, employment, or substance use, the new study examines community- and structural-level drivers--specifically, experiences of discrimination.

"Discrimination, in this instance related to race, sexual identity and HIV, is an important driver of health and life opportunities because it directly influences physical and mental health outcomes and can constrain access to education, jobs, and housing," says Philbin, the study's first author and Columbia Mailman School assistant professor of sociomedical sciences. "As we see in our new study, perceived discrimination--especially the experience of racism--placed the men in this study at an increased risk for arrest and incarceration."

While some studies have examined discrimination in the context of health outcomes like mental illness, these studies usually focused on single categories of discrimination--not intersectional discrimination of the kind experienced by individuals in this study. "To better understand the lived realities of people burdened with overlapping forms of discrimination, we must account for the compounding nature of these intersecting axes of social inequality," says Philbin. "We find that experiences of racism and discrimination based on sexual orientation and HIV status combine to raise these young men's risk for criminal justice involvement."

Participants completed four online surveys over the course of one year to assess the three predictors at baseline and criminal justice involvement at 3, 6, and 12-month follow-up (the study excluded men with criminal justice involvement at baseline). The researchers assessed discrimination through survey questions asking whether participants were, for example, treated with hostility/coldness by strangers, rejected by a potential sexual/romantic partner, denied a place to live, denied a job, and physically assaulted due to their race, sexual orientation; they also explored how individuals living with HIV were treated within their community.

Looking ahead, future research could focus on Black YMSM in other states beyond North Carolina to see if outcomes differ by geographic location. The research could also examine the effect of overlapping forms of discrimination in other groups, such as sexual minority Black women, Black transgender women, and other YMSM of color.

With the COVID-19 pandemic entering its second year, the challenges faced both by individuals and nations remain substantial. While notable medical advancements in the treatment of COVID-19 have been made, a host of questions about how to live with it and how to work to end it remain active.

Carnegie Mellon University researchers David Rode and Paul Fischbeck explore these questions in a new article, "On ambiguity reduction and the role of decision analysis during the pandemic," published in a special issue of the journal Risk Analysis dealing with the COVID-19 pandemic. One of Carnegie Mellon's traditional strengths is its multidisciplinary approach to decision making and Rode and Fischbeck suggest that the decision sciences collectively should have a major role to play in dealing with the virus.

The sciences and medicine are not the only fields struggling with the pandemic.

"In a very real sense, all of us, as individuals, face significant decisions about how to organize our lives right now," said Rode, adjunct research faculty with the Carnegie Mellon Electricity Industry Center. "These decisions range from simple questions, such as the safety of grocery shopping in person or air travel to the complex, such as government policies dealing with mandatory quarantines and compulsory vaccination."

In their article, Rode and Fischbeck note that many of the key decisions facing individuals, corporations and governments all depend on two basic values: the probability a person has the virus and the probability that person transmits the virus.

"The problem is that when we wrote the article neither of those values was known with any degree of certainty," said Fischbeck, professor of Social and Decision Sciences and Engineering and Public Policy. "Without those probabilities, there is ambiguity, which is a difficult environment in which to work for most decision makers."

"In order to reduce this ambiguity," noted Rode, "it's important to collect the right data."

This means collecting data on randomized samples of the population--not just people with symptoms. According to Rode and Fischbeck, this should have been done from the start.

"When the virus first became apparent," said Fischbeck, "testing resources were scarce and largely confined to people already displaying symptoms."

The problem, according to Rode and Fischbeck, was that such testing provided no useful information to guide decision making, and rarely impacted clinical decision making, since patients displaying symptoms were treated without regard to their test results.

"While useful, of course, for those individuals to know their status, this limited, non-randomized testing produced almost no value to policymakers trying to develop responses to the pandemic," said Rode. "How do you advise people to engage, or not engage, in certain activities if you can't determine how risky those activities are?"

"Even today, although we have a great deal more information about infections, we face the same ambiguities regarding wearing masks and vaccination," said Fischbeck. "The experts initially said people shouldn't wear masks; then masks only prevented infected people from spreading the virus but did not protect the wearer from catching it; then masks were effective in doing both; and then two weeks ago wearing two or three masks was 'common sense' and today, there are as of yet no benefits seen in wearing two masks. This ambiguity endures because we don't have the right data."

One of the key missing pieces of information has been the number of "hidden" cases, or undiagnosed individuals who have the virus, but do not display symptoms. These people are still capable of transmitting the virus, but because they are asymptomatic, they may take fewer precautions.

"We had only very rough ideas of the size of this population, because there was virtually no testing of asymptomatic people early on," said Rode. "This is the sort of information that large-scale randomized testing would reveal."

The article notes that, without this information, many mitigating strategies put in place are essentially "security theater"-- actions that make people feel safer without having an appreciable impact on actual risk. Or actions that incur costs in return for unknown benefits. How large a problem are asymptomatic vaccinated people?

In addition to the challenges created by an absence of data, Rode and Fischbeck raise potential problems that could arise from the presence of data. In the article, they write "disclosure informs, but it also divides."

"We mean that the availability of detailed demographic information on population infection rates must be treated with extreme caution," said Fischbeck.

"If 'certificates of immunity' or 'vaccine passports' are put in place, are groups with historically limited access to health care effectively barred from large aspects of public life? Should this form of COVID 'redlining' or 'profiling' be illegal, even if it is useful in limiting the spread of the virus?" said Rode. "There are important policy and ethical questions that must be part of the discussion, even if having the information would make society as a whole better off."

These questions, Rode and Fischbeck argue, create a clear need for the decision sciences to have a seat at the policy table.

The authors conclude that COVID-19 -- and future viruses like it -- are public health crises and solid, objective data are necessary to confront them. Reducing the ambiguity surrounding base rates and transmission rates is of considerable value to creating public health policy when testing is properly directed. But selective or misinterpreted data can also be a "virus." Released unintentionally or maliciously across social media, this "information virus" could cause societal harm to linger long after the physical harm is resolved. Careful application of the decision analyst's tools is essential to traverse this uncharted territory.

Wintertime outbreaks of COVID-19 have been largely driven by whether people adhere to control measures such as mask wearing and social distancing, according to a study published Feb. 8 in Nature Communications by Princeton University researchers. Climate and population immunity are playing smaller roles during the current pandemic phase of the virus, the researchers found.

The researchers -- working in summer 2020 -- ran simulations of a wintertime coronavirus outbreak in New York City to identify key factors that would allow the virus to proliferate. They found that relaxing control measures in the summer months led to an outbreak in the winter regardless of climate factors.

"Our results implied that lax control measures -- and likely fatigue with complying with control measures -- would fuel wintertime outbreaks," said first author Rachel Baker, an associate research scholar in Princeton's High Meadows Environmental Institute (HMEI). Baker and her co-authors are all affiliated with the HMEI Climate Change and Infectious Disease initiative.

"Although we have witnessed a substantial number of COVID-19 cases, population-level immunity remains low in many locations," Baker said. "This means that if you roll back enforcement or adherence to control measures, you can still expect a large outbreak. Climate factors including winter weather play a secondary role and certainly don't help."

The researchers found that even maintaining rigid control measures through the summer can lead to a wintertime outbreak if climate factors provided enough of a boost to viral transmission. "If summertime controls are holding the transmissibility of coronavirus at a level that only just mitigates an outbreak, then winter climate conditions can push you over the edge," Baker said. "Nonetheless, having effective control measures in place last summer could have limited the winter outbreaks we're now experiencing."

Cases have climbed in many northern hemisphere locations since November. In the United States, spikes in COVID-19 cases are thought to be tied to increased travel and gatherings for Thanksgiving and Christmas. Notably, outbreaks were recorded in temperate locations such as Los Angeles in addition to regions with much colder conditions, Baker said. At the same time, large outbreaks were observed in South Africa from November to January, which are that country's summer months.

"The greater incidence of COVID-19 in various environs really speaks to the climate's limited role at this stage," Baker said.

In May, the same authors published a paper in the journal Science suggesting that local climate variations would be unlikely to affect the coronavirus pandemic. The paper suggested that hopes that the warmer conditions of summer would slow the transmission of the novel coronavirus, SARS-CoV-2, in the northern hemisphere were unrealistic.

Gabriel Vecchi, a professor of geosciences and the High Meadows Environmental Institute and co-author of both studies, said that the virus currently spreads too quickly and that people are too susceptible for climate to be a determining factor.

"The influence of climate and weather on infection rates should become more evident -- and thus a potentially useful source of information for disease prediction -- as growing immunity moves the disease into endemic phases from the present epidemic stage," Vecchi said.

The most recent study provides insight on how scientists can determine the impact of various factors on the virus at various times, said co-author C. Jessica Metcalf, associate professor of ecology and evolutionary biology and public affairs and an HMEI associated faculty member.

"An important challenge that we tackle here is balancing the role of many potential factors on the trajectory of the epidemic," Metcalf said. "As the pandemic progresses, both natural and vaccinal immunity will play an increasing role, underscoring the importance of developing a handle on the landscape of immunity."

Critical factors to consider when projecting the future of COVID-19 are emerging variants of the virus, as well as how efforts to contain coronavirus have changed other diseases, said co-author Bryan Grenfell, the Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and Public Affairs and associated faculty in HMEI.

In November, Grenfell and his co-authors in the Climate Change and Infectious Disease initiative published a paper in the Proceedings of the National Academy of Sciences that non-pharmaceutical interventions (NPIs) such as mask wearing and social distancing could result in large, delayed outbreaks of endemic diseases such as influenza and respiratory syncytial virus (RSV).

"The interaction between NPIs and immunity will become even more complex as a variety of vaccines are deployed and new viral variants arise," Grenfell said. "Understanding the impact of these variables underlines the importance of immune surveillance and greatly expanded viral sequencing."

Additional authors of the current paper include Wenchang Yang, an associate research scholar in geosciences at Princeton.

Ancient Amazonian communities fortified valuable land they had spent years making fertile to protect it from conflict, excavations show.
Farmers in Bolivia constructed wooden defences around previously nutrient-poor tropical soils they had enriched over generations to keep them safe during times of social unrest.
These long-term soil management strategies allowed Amazonians to grow nutrient demanding crops, such as maize and manioc and fruiting trees, and this was key to community subsistence. These Amazonian Dark Earths, or Terra Preta, were created through burning, mulching, and the deposition of organic waste.
It was known that some communities built ditches and embankments, known locally as a zanja, around their settlements, which had suggested to act as a defensive structure. The examples from Bolivia were specifically constructed to also enclose the enriched soil and this is the first evidence of an additional fortification built in the ditch, demonstrating how important communities felt it was to protect their investment in the land.
Excavations, at the Versalles archaeological site along the Iténez River in the Bolivian Amazon, provide the first archaeological evidence that communities in the region built wooden palisades along with earthworks. The construction circles the outer perimeter of the village, enclosing and protecting homes and the enriched soil and forest.
Researchers had long speculated on the function of the zanjas and whether there had also been a palisade structure, but until now no direct evidence of a wooden construction had been found. The harsh tropical climate is unfavourable for the preservation of wooden architecture, but through careful excavation, the decomposed remains of the construction posts were detected in the soil. It is not possible to know what the structure would have looked like.
Archaeological analysis show that those living in Versalles began enriching soils around 500 BC. After almost two millennia, the zanja was constructed around AD 1300, at the same time as social unrest spread across Amazonia. The fortifications were later remodelled, including the addition of the palisade, around AD 1628 to 1803. Archaeological excavations suggests the community continued to thrive during this time, creating elaborate ceramics and producing a diversity of foods from staple crops to fruits and nuts, alongside fish and hunted animals.
The research, published in the journal Geoarchaeology, was conducted in collaboration with the modern Versalles community, by Dr.Mark Robinson and Professor. Jose Iriarte from the University of Exeter, Dr. Carla Jaimes?Betancourt, from the University of Bonn, Dr. Sarah Elliott, from Bournemouth University, and Dr. Yoshi Maezumi, from the University of Amsterdam, with students from the UK and Bolivia participating in excavations.
Dr Robinson said: "This is further evidence the Amazon is not a pristine place, untouched by human hands. People have had a great impact on the ecology of the rainforest. Communities invested heavily, generation after generation, to enrich the natural resources around them. As broad Amazon-wide social-unrest spread, the community felt the need to protect the resources into which they and their ancestors had invested so much."

Announcing a new article publication for BIO Integration journal. In this review article the authors Yue Li, Zhiyi Chen and Shuping Ge from First Affiliated Hospital of University of South China, Hengyang, China and Tower Health and Drexel University, Philadelphia, PA, USA summarize current state of the art applications of microbubble-cell interactions and sonoporation effects to cellular functions.

Ultrasound combined with microbubble-mediated sonoporation has been applied to enhance drug or gene intracellular delivery. Sonoporation leads to the formation of openings in the cell membrane, triggered by ultrasound-mediated oscillations and destruction of microbubbles. Multiple mechanisms are involved in the occurrence of sonoporation, including ultrasonic parameters, microbubbles size, and the distance of microbubbles to cells. Recent advances are beginning to extend applications through the assistance of contrast agents, which allow ultrasound to connect directly to cellular functions such as gene expression, cellular apoptosis, differentiation, and even epigenetic reprogramming.

LA JOLLA, CA--As new COVID-19 variants begin to throw vaccine efficacy in question, two leading scientists are calling for health agencies to invest in the development of vaccines that would be broadly effective against many different variants and strains of potential pandemic viruses.

In a commentary article published in the journal Nature, Dennis Burton, PhD, and Eric Topol, MD, of Scripps Research call for governments to provide significant funding support for rational vaccine design based on broadly neutralizing antibodies.

Such antibodies provide broad-spectrum potency against viruses, a valuable characteristic that opens the door to vaccines that could provide immunity against the many variants that might evolve from a fast-mutating virus. They could also be used as drugs to prevent and treat infections.

Burton and Topol note that the rapid development of effective vaccines against COVID-19 was possible due to certain properties of the SARS-CoV-2 virus--in particular, the spike protein on the virus's surface. But they warn that the virus driving the next pandemic may not provide such a ready target, which could substantially slow the process of developing a novel vaccine.

"Even SARS-CoV-2 could be becoming more problematic for vaccines because of the emergence of new variants," they write. "We call for an alternative approach to pandemic preparedness."

Burton and Topol point to broadly neutralizing antibodies as a promising avenue for developing vaccines and therapies that might be readily adapted to newly emerged pandemic viruses or those that rapidly evolve to evade traditional vaccines.

"Such antibodies could be used as first-line drugs to prevent or treat viruses in a given family, including new lineages or strains that have not yet emerged," the write. "More importantly, they could be used to design vaccines against many members of a given family of viruses."

Of particularly concern for future pandemics are viruses that are "evasion-strong," meaning their biological characteristics make them challenging to treat with drugs or prevent with vaccines. The extreme example of this type of virus is HIV, which can stay in the body for years, hiding from the host's immune system.

Burton and his colleagues at Scripps Research and other organizations are currently developing vaccines based on broadly neutralizing antibodies in hopes of producing the world's first truly effective HIV vaccines.

They are also seeking to employ broadly neutralizing antibodies as therapies and vaccines against influenza, another evasive virus and prime contender for future pandemics.

"Such pan-virus vaccines could be made in advance and deployed before the next emerging infection becomes a pandemic," Burton and Topol write. "We call for an investment now in basic research leading to the stockpiling of broadly effective vaccines."

Photoplethysmography (PPG) is a simple optical technique used to detect volumetric changes in peripheral blood circulation. It's used in smart watches, for example, to monitor pulse and heart rate, but PPG biosensors are also found in millions of smartphones, but without any current clinical applications.

In a study published online in the February 2021 issue of Chest, researchers at University of California San Diego School of Medicine, with industry collaborators, found that already embedded PPG in smartphones, in tandem with application software, could be used for remote clinical pulse oximetry to manage chronic cardiopulmonary disease and perhaps initial treatment and monitoring of persons affected in respiratory viral pandemics, such as COVID-19.

"Pulse oximetry monitoring plays an important role in managing pulmonary diseases, especially during pandemics or epidemics of respiratory viral infections, such as COVID-19 and influenza," said the study's first author Sara H. Browne, MD, an associate professor in the UC San Diego School of Medicine and an infectious disease specialist.

Oxygen saturation is a valuable component of the clinical evaluation used to differentiate those that require close monitoring. In circumstances of home quarantine, remote clinical pulse oximetry allows patients to objectively report oxygen saturation and heart rate in addition to their symptoms. Smartphone sensors with apps could facilitate access to these measurements, but to be utilized clinicians must know that these measurements are accurate and reliable.

Browne also noted there are health equity aspects in remote monitoring.

"Smartphones with sensors and apps could significantly enhance remote monitoring due to their ubiquity, and don't require patients to have additional expensive gadgets."

PPG sensors measure distention or enlargement of arteries and other vessels under the skin as blood pulses through them by detecting differences in light absorbed or reflected back to a pair of light-emitting diodes in the device. The painless, non-invasive technology is called pulse oximetry and is commonly used in hospitals and clinics, often to evaluate oxygen levels in patients' blood.

In their study, researchers recruited 10 volunteers (three Caucasian, three Black and four Asian), each placed an index finger over a smartphone sensor system with an app designed to clinically interpret the resulting optical data. The volunteers then breathed a mixture of gases with reduced levels of oxygen, sequentially declining to reach stable arterial oxygen saturations between 70 percent and 100 percent. They found that the smartphone measurements of blood-oxygen levels corresponded with other Food and Drug Administration-approved clinical tools used for this purpose.

Then, using the same smartphone, the researchers analyzed more than 2,200 readings taken simultaneously from smartphone pulse oximetry and in-hospital Welch-Allyn instruments in 320 study participants, ages 18 to 89, and representing a broad range of racial and ethnic backgrounds. They found that the smartphone readings had equivalent measurement accuracy and precision to the expensive FDA-approved hospital instruments.