Culture

In the field of molecular epidemiology, the worldwide scientific community has been steadily sleuthing to solve the riddle of the early history of SARS-CoV-2. Despite recent efforts by the World Health Organization, no one to date has identified the first case of human transmission, or "patient zero" in the COVID-19 pandemic.

Finding the earliest possible case is needed to better understand how the virus may have jumped from its animal host first to infect humans as well as the history of how the SARS-CoV-2 viral genome has mutated over time and spread globally.

Since the first SARS-CoV-2 virus infection was detected in December 2019, well over a million genomes of SARS-CoV-2 have been sequenced worldwide, revealing that the coronavirus is mutating, albeit slowly, at a rate of 25 mutations per genome per year. The sheer number of emerging variants, including the UK (B.1.1.1.7), South African (B.1.351), South American (P.1) and now, Indian (B.1.617) have not only come to replace prior dominant strains in their respective regions, but still threaten world health due to their potential to escape today's vaccines and therapeutics.

"The SARS-CoV-2 virus has already infected more than 145 million people and caused 3 million deaths across the world," said Sudhir Kumar, director of the Institute for Genomics and Evolutionary Medicine, Temple University. "We set out to find the genetic common ancestor of all these infections, which we call the progenitor genome."

This progenitor genome (proCoV2) is the mother of all SARS-CoV-2 coronaviruses that has infected and continue to infect people today.

In the absence of patient zero, Kumar and his research team now may have found the next best thing to aid the worldwide molecular epidemiology detective work. "We reconstructed the genome of the progenitor and its early pedigree by using a big dataset of coronavirus genomes obtained from infected individuals since December 2019," said Kumar, the lead author of a new study, appearing in advanced online edition of the journal Molecular Biology and Evolution.

They found that the progenitor gave rise to a family of coronavirus strains, whose members included the strains found in Wuhan, China, in December 2019. "In essence, the events in December in Wuhan, China, represented the first superspreader event of a virus that had all the tools necessary to cause a worldwide pandemic right out of the box." said Kumar.

Kumar's group estimates that the SARS-CoV-2 progenitor was already circulating with an earlier timeline--at least 6 to 8 weeks prior to the first genome sequenced in China, known as Wuhan-1. "This timeline puts the presence of proCoV2 in late October 2019, which is consistent with the report of a fragment of spike protein identical to Wuhan?1 in early December in Italy, among other evidence," said Sayaka Miura, a senior author of the study.

"We have found progenitor genetic fingerprint in January 2020 and later in multiple coronavirus infections in China and the USA. The progenitor was spreading worldwide months before and after the first reported cases of COVID-19 in China," said Pond.

Besides their findings on SARS-CoV-2's early history, Kumar's group also has developed intuitive mutational fingerprints and Greek symbol classification (ν, α, β, γ, δ, and ε) to simplify the categorization of the major strains, sub-strains and variants infecting an individual or colonizing a global region. This may help scientists better trace and provide context for the order of emergence of new variants.

"Overall, our mutational fingerprinting and nomenclature provide a simple way to glean the ancestry of new variants as compared to phylogenetic designations, e.g., B.1.351 and B.1.1.7," said Kumar.

For example, an α fingerprint refers to genomes that one or more of the α variants and no other subsequent major variants, and αβ fingerprint refers to genomes that contain all α, at least one β variant, and no other major variants.

"With our tools, we observed the spread and replacement of prevailing strains in Europe (αβε with αβζ) and Asia (α with αβε), the preponderance of the same strain for most of the pandemic in North America (αβ?δ), and the continued presence of multiple high?frequency strains in Asia and North America," said Pond.

Getting to the root of the problem

To identify the progenitor genome, they used a approach not applied to SARS-CoV-2 previously, called mutation order analysis. The technique, which is used extensively in cancer research, relies on a clonal analysis of mutant strains and the frequency in which pairs of mutations appear together to find the root of the virus.

Many previous attempts in analyzing such large datasets were not successful because of "the focus on building an evolutionary tree of SARS-CoV-2," says Kumar. "This coronavirus evolves too slow, the number of genomes to analyze is too large, and the data quality of genomes is highly variable. I immediately saw parallels between the properties of these genetic data from coronavirus with the genetic data from the clonal spread of another nefarious disease, cancer."

Kumar and Miura have developed and investigated many techniques for analyzing genetic data from tumors in cancer patients. They adapted and innovated these techniques to build a trail of mutations that traced back to the progenitor genetic fingerprint. "The mutation tracking approach produced the progenitor and the family history of its major mutation. It is a great example of how big data coupled with biologically-informed data mining reveals important patterns," said Kumar.

An earlier timeline emerges
"This progenitor genome had a sequence very different from what some folks are calling the reference sequence, which is what was observed first in China and deposited into the GISAID SARS-CoV-2 database," said Kumar.

The closest match was to eight genomes sampled 26 to 80 days after the earliest sampled virus from 24 December 2019. Multiple close matches were found in all sampled continents and detected as late as June 2020 (pandemic day 181) in South America. Overall, 140 genomes Kumar's group analyzed all contained only synonymous differences from proCoV2. That is, all their proteins were identical to the corresponding proCoV2 proteins in the amino acid sequence. A majority (93 genomes) of these protein-level matches were from coronaviruses sampled in China and other Asian countries.

These spatiotemporal patterns suggested that proCoV2 already possessed the full repertoire of protein sequences needed to infect, spread and persist in the global human population.

They found the proCoV2 virus and its initial descendants arose in China, based on the earliest mutations of proCoV2 and their locations. Furthermore, they also demonstrated that a population of strains with at least three mutational differences from proCoV2 existed at the time of the first detection of COVID-19 cases in China. With estimates of SARS-CoV-2 acquiring 25 mutations per year, this meant that the virus must already have been infecting people several weeks before the December 2019 cases.

Mutational signatures

Because there was strong evidence of many mutations before the ones found in the reference genome, Kumar's group had to come up with a new nomenclature of mutational signatures to classify SARS-CoV-2 and account for these by introducing a series of Greek letter symbols to represent each one.

For example, they found that the emergence of α SARS-CoV-2 genome variants came before the first reports of COVID-19. This strongly implies the existence of some sequence diversity in the ancestral SARS-CoV-2 populations. All 17 of the genomes sampled from China in December 2019, including the designated SARS-CoV-2 reference genome, carry all three α variants. But, 1,756 genomes without α variants were sampled across the world until July 2020. Therefore, the earliest sampled genomes (including the designated reference) were not the progenitor strains.

It also predicts the progenitor genome had offspring that were spreading worldwide during the earliest phases of COVID-19. It was ready to infect right from the start.

"The progenitor had all the ability it needed to spread," said Pond. "There is an overabundance of non-synonymous changes in the population. What happened between bats and humans remains unclear, but proCoV2 could already infect at pandemic scales."

A global spread

Altogether, they have identified seven major evolutionary lineages and the episodic nature of their global spread. The proCoV2 genome gave rise to many major offspring lineages, some of which arose in Europe and North America after the likely genesis of the ancestral lineages in China.

"Asian strains founded the whole pandemic," said Kumar. "But over time, many variants
that evolved elsewhere are now infecting Asia much more."

Their mutational-based analyses also established that North American coronaviruses harbor very different genome signatures than those prevalent in Europe and Asia.

"This is a dynamic process," said Kumar. "Clearly, there are very different pictures of spread that are painted by the emergence of new mutations, the three εs, γ&delta, which we found to occur after the spike protein change (a β mutation). Scientists are still figuring out if any functional properties of these mutations have sped up the pandemic."

Remarkably, the mutational signature of αβ?δ has remained the dominant lineage in North America since April 2020, in contrast to the turn?over seen in Europe and Asia. More recently, novel fast?spreading variants including an S protein variant (N501Y) from South Africa and the UK (B.1.1.17) have rapidly increased. Coronaviruses with N501Y variant in South Africa carry the αβγδ genetic fingerprint, whereas those in the UK carry the αβε genetic fingerprint, according to their classification scheme. "Therefore, αβ ancestor continues to give rise rise to many major offshoots of this coronavirus." Said Kumar.

Real-time updates

The MBE study relied on three snapshots were retrieved from GISAID on July 7, 2020, (a dataset of 60,332 genomes), October 12, 2020, (contained 133,741 genomes), and finally, an expanded dataset of 172,480 genomes sampled on December 30, 2020.

Moving forward, they will continue to refine their results as new data becomes available.

"More than a million SARS-CoV-2 genomes are sequenced now," said Pond. "The power of this approach is that the more data you have, the more easily you can tell the precise frequency of individual mutations and mutation pairs. These variants that are produced, the single nucleotide variants, or SNVs, their frequency, and history can be told very well with more data. Therefore, our analyses infer a credible root for the SARS-CoV-2 phylogeny."

The MBE study is part of their effort to maintain a continuous, live real-time monitoring of SARS-CoV-2 genomes, which has now grown to include more than 350,000 genomes.

"We have set up a live dashboard showing regularly updated results because the processes of data analysis, manuscript preparation, and peer?review of scientific articles are much slower than the pace of expansion of SARS?CoV?2 genome collection," said Pond. "We also provide a simple "in?the? browser" tool to classify any SARS?CoV?2 genome based on key mutations derived by the MOA analysis.

"These findings and our intuitive mutational fingerprints and barcodes of SARS-CoV-2 strains have overcome daunting challenges to develop a retrospective on how, when and why COVID-19 has emerged and spread, which is a prerequisite to creating remedies to overcome this pandemic through the efforts of science, technology, public policy and medicine," said Kumar.

DALLAS, May 4, 2021 -- A meta-analysis of 14 air pollution studies from around the world found that exposure to high levels of air pollutants during childhood increases the likelihood of high blood pressure in children and adolescents, and their risk for high blood pressure as adults. The study is published in a special issue on air pollution in the Journal of the American Heart Association, an open access journal of the American Heart Association.

Other studies look at: the effects of diesel exhaust on the muscle sympathetic nerve; the impact of pollutants on high blood pressure; rates of hospital readmission for heart failure among those exposed to high levels of ambient air pollution; and risk of stroke and heart attack after long-term exposure to high levels of particulate matter. The studies include health outcomes of people who were exposed to pollutants in the United States, China and Europe.

High blood pressure during childhood and adolescence is a risk factor for hypertension and heart disease in adulthood. Studies on air pollution and blood pressure in adolescents and children, however, have produced inconsistent conclusions. This systematic review and meta-analysis pooled information from 14 studies focused on the association between air pollution and blood pressure in youth. The large analysis included data for more than 350,000 children and adolescents (mean ages 5.4 to 12.7 years of age).

"Our analysis is the first to closely examine previous research to assess both the quality and magnitude of the associations between air pollution and blood pressure values among children and adolescents," said lead study author Yao Lu, M.D., Ph.D., professor of the Clinical Research Center at the Third Xiangya Hospital at Central South University in Changsha, China, and professor in the department of life science and medicine at King's College London. "The findings provide evidence of a positive association between short- and long-term exposure to certain environmental air pollutants and blood pressure in children and adolescents."

The analysis included 14 studies published through September 6, 2020, exploring the impact of long-term exposure (?30 days) and/or short-term exposure (

The studies were divided into groups based upon length of exposure to air pollution and by composition of air pollutants, specifically nitrogen dioxide and particulate matter with diameter ?10 μm or ?2.5 μm. (The majority of research linking heart disease with particulate matter focuses on particle matter mass, which is categorized by aerodynamic diameter - μm or PM.) Fine particles are defined as PM2.5 and larger; coarse particles are defined at PM10; and the concentrations of particulate matter are typically measured in their mass per volume of air (μg/m3).

The meta-analysis concluded:

Short-term exposure to PM10 was significantly associated with elevated systolic blood pressure in youth (the top number on a blood pressure reading).

Periods of long-term exposure to PM2.5, PM10 and nitrogen dioxide were also associated with elevated systolic blood pressure levels.

Higher diastolic blood pressure levels (the bottom number on a blood pressure reading) were associated with long-term exposure to PM2.5 and PM10.

"To reduce the impact of environmental pollution on blood pressure in children and adolescents, efforts should be made to reduce their exposure to environmental pollutants," said Lu. "Additionally, it is also very important to routinely measure blood pressure in children and adolescents, which can help us identify individuals with elevated blood pressure early."

The results of the analysis are limited to the studies included, and they did not include data on possible interactions between different pollutants, therefore, the results are not generalizable to all populations. Additionally, the analysis included the most common and more widely studied pollutants vs. air pollutants confirmed to have heart health impact, of which there are fewer studies.

Durham, NC - A study released today in STEM CELLS Translational Medicine offers hope for those suffering from a chronic, difficult to treat condition called non-tuberculous mycobacteria (NTM) lung infection. The study describes how researchers at Case Western University developed a new model of NTM lung infection and then used it to show how effective human mesenchymal stem cells (hMSCs) are in treating this condition - and even which donor cells might be best for doing so.

"The potential to use human mesenchymal stem cells to treat difficult lung infections is promising," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and Director of the Wake Forest Institute for Regenerative Medicine. "This study shows the ability of using optimal donors to obtain maximum treatment success."

NTMs are naturally occurring, and everyone inhales them into their lungs as part of daily life. For most people, they are harmless. But in a small number of vulnerable individuals, such as older people or those with cystic fibrosis (CF) or COPD, NTM bacteria can settle in the lungs and cause infection. While not contagious, more than 100,000 people are living with NTM lung disease in the U.S. alone, and that rate appears to be increasing.

"NTM infections can be very difficult to resolve," said Tracey L. Bonfield, Ph.D., the study's corresponding author. "Treatment typically requires taking multiple antibiotics, often for years. Patients who suffer from chronic NTM infection not only deal with the consequences of the disease, but also the toxicity, as well as inefficiency and side effects of the antibiotics used to treat it."

In the search for better therapies, some researchers are focusing on hMSCs, which are collected from adults and can be coaxed into becoming a variety of cells types. hMSCs have significant potential for treating infection and inflammation, Dr. Bonfield said. "They are dynamic storehouses of anti-microbial activity. They are unique in their capacity to respond to infection by secreting multiple bioactive factors, contributing to the host environment. That gives hMSCs a clinical advantage over traditional pharmaceuticals."

Previous studies by the Bonfield team described the potential for hMSCs and their secreted products ("supernatants") to treat other types of lung infections including Pseudomonas aeruginosa and Staphylococcus aureus, but these studies are the first to describe the ability of hMSCs to manage two of the most problematic groups of NTMs, Mycobacterium avium (M. avium) and Mycobacterium intracellulare (M. intracellulare). Like these current studies, hMSCs demonstrated significant anti-microbial, anti-inflammatory and anti-fibrotic potential, both in culture medium (in vitro) and in animals (in vivo). Further, they also documented that hMSC treatment improves the effectiveness of antibiotics, leading to a decrease in the dose necessary for eradicating bacteria.

At the same time, those studies pointed out that not all hMSC preparations have the same level of potency or sustainability. "This suggested to us that it is essential to identify the appropriate hMSC donor and subsequent preparation for disease specific applications. That was the goal of our current study," said Dr. Bonfield.

Both M. avium and M. intracellulare are slow growing bacteria, so researchers have found it difficult to study what happens in sustained NTM infections because in small animals the bacteria clear up quickly, while larger animals are too expensive for defining dosing, timing and duration of a new treatment, Dr. Bonfield noted. So, her team first needed to develop new models of M. avium and M. intracellulare lung infections that would effectively allow them to study this issue.

"In the earlier studies we had developed an innovative protocol in which M. avium and M. intracellulare can be evaluated over the course of a week instead of the typical four to six weeks," Dr. Bonfield explained. To sustain infection in vivo for chronic disease required an additional innovation "We did this by embedding NTMs into beads of a polysaccharide extracted from seaweed called agarose, and then injecting them into mice with CF. The beads degrade gradually, releasing the NTM into the mice and thus extending the time of infection and inflammatory response. This modeling system has been very efficient in generating acute and chronic scenarios of infection in all of our models."

The researchers then went on to identify donor-specific hMSC potency against M. avium and M. intracellulare, once again in vitro and in vivo using CF mice. "Every donor hMSC preparation has a unique profile in terms of how the cells respond to pathogens, which likely translates into their successful potency and how the patient responds to hMSC treatment," Dr. Bonfield said.

"Focusing on hMSC response to NTMs and efficiency of in vitro and in vivo anti-NTM activity provides direction for identifying the optimal hMSC signature for anti-NTM therapy. Data gained from our study begins to define this unique hMSC fingerprint."

Osaka, Japan —Straight-line constant-speed propagation in free space is a basic characteristic of light. In a recent study published in Communications Physics, researchers from Osaka University discovered the phenomenon of reciprocating propagation of laser pulse intensity in free space.

Spatiotemporal couplings have been recently used to produce light with tunable group-velocity, direction, and trajectory in free space. For example, the flying focus (a moving laser pulse intensity in the extended Rayleigh length), where longitudinal chromatism and temporal chirp are combined to control the spectrum-dependent focus-separation in space and spectrum-dependent pulse-location in time, respectively, has arbitrarily tunable propagating group-velocity and direction in space and time.

However, in the previous result, the flying focus can only propagate along a certain direction either forward or backward, although the propagating group-velocity can be freely controlled.

In this study, by dramatically increasing the Rayleigh length in space and the temporal chirp in time, the newly created flying focus propagates along a reciprocating straight-line trajectory in free space. A clear reciprocating flying focus with a high spatial resolution is also possible by further increasing the temporal chirp.

"The newly created flying focus propagates along the longitudinal axis first forward, then backward, and lastly forward again, showing a reciprocating straight-line trajectory in space and time. The forward-propagating velocity is the light speed in the vacuum, while the backward-propagating velocity is subluminal," explains corresponding author Zhaoyang Li.

This intriguing phenomenon changes the traditional understanding of light propagation and may be applied in both fundamental and applied physics.

"For example, in our radiation pressure simulation, it can produce an on-axis reciprocating trapping or pushing force for a small or big sphere, respectively, in the Rayleigh scattering regime," says Zhaoyang Li.

Cancer of the colon and rectum is one of the deadliest forms of cancer, and has in recent years affected growing numbers of young people. In the largest registry study to date, researchers at Karolinska Institutet in Sweden and Harvard University in the USA demonstrate a possible connection between colorectal polyps in close relatives and the risk of developing colorectal cancer. The study, which is published in the British Medical Journal, is of potential consequence for different countries' screening procedures.

Colorectal cancer is the second deadliest form of cancer in the world, according to the World Health Organisation (WHO). While lifestyle factors, such as overweight and sedentariness, increase the disease risk, there is also a known hereditary factor.

Most people diagnosed with the disease are over 65, but in a growing number of countries the proportion of young people affected is increasing.

Local colorectal cancer can be treated with a good prognosis; prospects are much worse, however, for patients with metastases.

In Sweden, people over 65 are offered colonoscopy screening, but more knowledge is needed about which individuals should be offered this prophylactic examination.

The disease is preceded by polyps in the mucosa of the colon. Researchers at Karolinska Institutet and Harvard University have now conducted the largest registry study to date on the relationship between colorectal cancer, and having a first-degree relative (i.e. parents and siblings) with a colorectal polyp.

The study included 68,060 patients with colorectal cancer and 333,753 healthy controls matched for parameters such as age and sex. Data on colorectal cancer and polyps were sourced from the ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden) cohort.

All other patient data were drawn from Swedish healthcare registries. The researchers also took the hereditariness of colorectal cancer into account.

They found that approximately 8.4 per cent of the participants with colorectal cancer had a sibling or parent with colorectal polyps, as opposed to 5.7 per cent of the control group.

The results show that heredity for colorectal polyps had a 40 per cent increased risk of colorectal cancer. The researchers found what appear to be several hereditary risk relationships.

"The risk was double in people with at least two first-degree relatives with polyps or a first-degree relative who had a colorectal polyp diagnosed before the age of 60." says the study's first author Mingyang Song, researcher at Harvard University.

A weakness of the study is the lack of information on other risk factors of colorectal cancer, such as lifestyle factors as well as the size and spread of the polyps. More research is now needed to corroborate the results.

"If additional studies reveal a link between a family history of polyps and the risk of colorectal cancer, it is something to take into account in the screening recommendations, especially for younger adults," says Jonas F. Ludvigsson, paediatrician at Orebro University Hospital and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. "I really hope that this study can help doctors in Sweden and elsewhere identify patients at a higher risk of colorectal cancer."

The study was financed by the National Institutes of Health and the American Cancer Society. Jonas F. Ludvigsson heads an unrelated study commissioned by the Swedish IBD Quality Registry (SWIBREG) financed by Janssen. There are no other reported conflicts of interest.

PULLMAN, Wash. -- Professor Arda Gozen looks to a future someday in which doctors can hit a button to print out a scaffold on their 3-D printers and create custom-made replacement skin, cartilage, or other tissue for their patients.

Gozen, George and Joan Berry associate professor in the Washington State University School of Mechanical and Materials Engineering, and a team of researchers have developed a unique scaffolding material for engineered tissues that can be fine-tuned for the tricky business of growing natural tissue. They report on their research in the journal, Bioprinting. The team also includes researchers from WSU's Gene and Linda Voiland School of Chemical Engineering and Bioengineering as well as from the University of Texas-San Antonio (UTSA), Morehouse College, and University of Rochester. The lead author is Mahmoud Amr, who received his PhD at UTSA.

In recent decades, researchers have been working to use biological material in 3D printing to create tissue or organs for patients recovering from injury or disease. Using 3D printing, or additive manufacturing, makes it possible to print complex, porous, and personalized structures and could allow doctors someday to print out tissue for a patient's particular body and needs. To create biological structures, biological materials known as "bioinks" are dispensed out of a nozzle and deposited layer-by-layer, creating complex "scaffolds" for real biological material and providing a nice place for cells to grow.

Nature, however, has so far been more complicated than researchers can keep up with. Real biological cells like to grow on a scaffold that approaches their own properties. So, for instance, a skin cell wants to grow on a scaffold that feels like skin while a muscle cell will only develop on a scaffold that feels like muscle.

"The success of this method in manufacturing functional tissues relies heavily on how well the fabricated structures mimic the native tissues," Gozen said. "If you want to grow cells and turn them into functional tissue, you need to match the mechanical environment of the native tissue."

The way that researchers have traditionally varied their scaffolds was to simply remove trusses to make them softer or stiffer - a method that is too simple to address all the needed complexity in tissue engineering.

"We don't have a lot of knobs to turn," Gozen said. "You need more degrees of freedom - to create something softer or harder without changing the structure."

The team of researchers developed a new bioink material that allows for customizing properties to closer approach what cells might need. The ingredients for their scaffold include gelatin, gum Arabic, and sodium alginate, which are all common thickening agents used in many processed foods.

Similar to the way a thick rope is made of braided strands, the researchers used three separate chemical processes to tie their three ingredients together into one scaffold material for printing.

Playing with the separate chemical processes then provides a way to finely tune the mechanical properties of the material, allowing them to make a softer or stiffer final scaffold.

"That gives you the capability of tuning the properties without changing the scaffold design and gives you an additional degree of freedom that we are seeking."

By adjusting the chemical bonds between the rope strands, they didn't change the material significantly, and it was amenable for growing cartilage cells.

The work is still in its early stages, and the researchers would like to figure out how to more precisely tune the process and final material. They might look at varying the composition of their three materials or printing at different temperatures, for instance.

Trying to imitate the vast complexity of natural tissue remains a challenge. Even a simple millimeter-sized piece of cartilage on the knee for instance, has three separate and distinct layers, each with different mechanical properties and functions.

"You're not assembling Legos here. It's always about replicating nature that works with the body," Gozen said. "You can make living structures, but they look nothing like the native tissue. Precision is key because there is no single mechanical property target for a single piece of tissue."

Dating violence - physical, sexual, psychological or emotional within a relationship, including stalking - is pervasive on college campuses with far-reaching health implications. One in five women experience a sexual assault in college and students living in sorority houses are three times more likely to experience rape. College students are vulnerable to dating violence because of the influence of their social and living environments.

Researchers from Florida Atlantic University's College of Education in collaboration with Sacred Heart University conducted a study to understand the dating violence experience and perpetration of college-age women, as well as how they conceptualize violence in dating relationships. They also wanted to learn more about the role of technology within their lived experiences, which infuses most areas of American life, especially in dating and romantic relationships. Mobile technology allows 24-hour access, which also facilitates stalking and controlling behaviors.

Results of the study, published in the journal Violence Against Women, illuminate the span of dating violence knowledge among the participants and point to a lack of understanding of what constitutes emotional violence. Findings reveal normalization of unhealthy violent behaviors where sexual pressure or sexualized verbal harassment are viewed as an innate part of men, supporting the idea that "boys will be boys."

"Physically forcing you to have intercourse," was endorsed at 100 percent by participants as violent, while "emotionally pressuring you to have intercourse until you give in," was endorsed at 73.9 percent. Both scenarios indicate rape, yet one of them introduced physical dating violence, which was not acceptable to any participant. The other item introduced coercive sex, which was acceptable to about 25 percent of the participants.

Fifty-eight percent of the study participants reported not knowing how to help someone experiencing dating violence, 57 percent reported difficulty identifying what constitutes dating violence, and 38 percent noted not knowing how to get help for themselves if experiencing dating violence.

A substantially lower percentage of participants reported not experiencing in-person violence, but did report the experience of intimate partner "cyber" violence. Almost every respondent who noted having experienced intimate partner sexual, physical and emotional violence also documented experiencing intimate partner cyber violence.

Participants expressed a decreased sense of personal control over impulsivity and retaliatory behaviors when using technology in relationships, while often justifying the use of this form of violence because of the accessibility of technology. They also described ways in which they were controlled and monitored by partners.

"Unfortunately, the college students in our study demonstrated a lack of knowledge of the forms of dating violence and its consequences. They also had a tendency to normalize these behaviors, which led to acceptance, rationalizing and providing excuses for these acts of violence. Furthermore, they lacked awareness of support systems that are available," said Kelly Emelianchik-Key, Ph.D., senior author and an associate professor in the Department of Counselor Education within the College of Education.

Study participants failed to mention any resources for psychological services, therapy, prevention programming or dating violence support groups. Only 21.6 percent endorsed the desire to seek help specifically from a counselor, traditionally one of the primary services provided on most college campuses. Instead, study participants turned to peers for help. However, research has shown that peers do not know how to help and fear intruding into someone's relationship.

"Our study findings underscore the need for education and early prevention programs on campuses that give a clear message that violence - in all forms - is not acceptable or normal in relationships," said Carman S. Gill, Ph.D., co-author, professor and department chair in the clinical mental health program, FAU College of Education. "Moreover, women should recognize emotional violence as a predictor of low quality of life over time and emotional well-being. The importance of understanding emotional abuse cannot be understated, as research findings illustrate that emotional violence is just as detrimental as physical violence."

The researchers say that because it is evident that peers play a critical role in student growth and development, interventions such as peer training initiatives, need to be appropriately targeted across college campuses. They also note that to break this cycle, students could benefit from a university/college statement or policy of zero tolerance for all forms of dating violence perpetration, along with clear definitions of the forms of violence.

"By gaining a critical understanding of college women's unique experiences, we can tailor early intervention to meet the individual needs of this population before the violence becomes pervasive and affects their physical and emotional health," said Emelianchik-Key.

Aging is the biggest risk factor for perturbation of the nervous system, even in the absence of distinct disease or trauma. For yet unknown reasons, the impulse conducting, myelinated projections and synaptic connections between nerve cells are especially vulnerable to aging-related degeneration. These pathological alterations often manifest as cognitive, sensory, and motor decline in older adults and represent a serious socio-economic challenge.

Malactivation leads to damage

Scientists have long assumed that inflammation plays an important role in this process. Mal- or overactivation of distinct cells belonging to the innate immune system - the microglia - appears to promote damage of nerve fibers and synapses in the aging central nervous system (CNS). In a recent project, scientists of the University Hospital Würzburg have now discovered an important role of the adaptive immune system.

The study was conducted at the Department of Neurology under corresponding author and lecturer Dr. Janos Groh from the section of "Developmental Neurobiology" (Prof. Dr. Rudolf Martini) in collaboration with Professor Wolfgang Kastenmüller (Institute for Systems Immunology) and Dr. Antoine-Emmanuel Saliba from the Helmholtz Institute for RNA-based Infection Research. The results of the study have now been published in the scientific journal Nature Aging.

T cells as mediators of neurodegeneration

"Cytotoxic CD8+ T cells normally recognize and fight infected or malignant cells. However, in case of autoimmune diseases like multiple sclerosis, they can also do unwanted damage in the nervous system", says Janos Groh. The scientists could previously identify such CD8+ T cells as important disease amplifiers in models of various genetically mediated neurological disorders. Their role in the aging CNS, however, was so far poorly investigated on a functional level. In order to shed light on this question, the researchers investigated the impact of CD8+ T cells in aged mice, where these cells were found in increased numbers in fiber tracts.

"We show that the accumulation of CD8+ T cells leads to degeneration of nerve fibers in the CNS of normal aging mice, which contributes to motor and cognitive decline", Groh summarizes the most important results of the study. Using modern gene expression analyses on the single-cell level, the team could for the first time characterize distinct populations of these CD8+ T cells in the brains of adult and aged mice in detail. This helped the scientists to subsequently clarify how the CD8+ T cells cause harm in the brain using precise immunological animal experiments.

Inflammation as a risk as well as therapeutic opportunity

"In addition, we show that T cell-mediated damage in aged but not adult mice is aggravated by systemic inflammation", Groh adds. According to him, the study therefore confirms that CD8+ T cells are important effectors of inflammation-driven damage to the aging CNS, for example also after infections at more distant sites of the body. In future studies, the researchers want to clarify why and how exactly this inflammatory response is initiated.

Finally, the scientists could find very similar T cell reactions as observed in mice also in autopsies of CNS white matter from older humans. CD8+ T cells might therefore represent a putative target for therapeutic approaches to mitigate aging-related decline of structure and function of the nervous system. The study thus provides basic-scientific and translationally relevant insights into degenerative aging-related processes and another example for the complex interaction between the nervous and the immune system.

Abu Dhabi, UAE, May 3, 2021: Researchers from NYU Abu Dhabi's Center for Genomics and Systems Biology have successfully sequenced the genome of previously extinct date palm varieties that lived more than 2,000 years ago. They did so using date palm seeds that were recovered from archaeological sites in the southern Levant region and radiocarbon-dated from the 4th century BCE to the 2nd century CE. The seeds were germinated to yield viable, new plants. The researchers conducted whole genome sequencing of these germinated ancient samples and used this genome data to examine the genetics of these previously extinct Judean date palms. This study marks the first time researchers have sequenced the genomes of plants from ancient germinated seeds.

By examining the genome of a species (Phoenix dactylifera L.) that thrived centuries ago, Professor of Biology Michael D. Purugganan and his NYUAD colleagues, along with research partners in Israel, and France, were able to see how these plants evolved over a period of time. In this case, they observed that between the 4th century BCE and 2nd century CE, date palms in the eastern Mediterranean started to show increasing levels of genes from another species, Phoenix theophrasti, which today grows in Crete and some other Greek islands, as well as southwestern Turkey, as a result of hybridization between species. They conclude that the increasing level of genes from P. theophrasti over this period shows the increasing influence of the Roman Empire in the eastern Mediterranean.

Their findings are reported in The genomes of ancient date palms germinated from 2,000-year-old seeds published in the journal Proceedings of the National Academy of Science USA.

"We are fortunate that date palm seeds can live a long time - in this case, more than 2,000 years - and germinate with minimal DNA damage, in the dry environment of the region," said Purugganan. "This 'resurrection genomics' approach is a remarkably effective way to study the genetics and evolution of past and possibly extinct species like Judean date palms. By reviving biological material such as germinating ancient seeds from archaeological, paleontological sites, or historical collections, we can not only study the genomes of lost populations but also, in some instances, rediscover genes that may have gone extinct in modern varieties."

What The Study Did: The findings of this study suggest an association between county-level income inequality and COVID-19 cases and deaths.

Authors: Michelle C. Odden, Ph.D., of Stanford University in Stanford, California, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.8799)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

What The Study Did: Inquiries to a child abuse hotline during the COVID-19 pandemic compared with inquiries during the same period the previous year are assessed in this study.

Authors: Robin Ortiz, M.D., of the University of Pennsylvania in Philadelphia, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2021.0503)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

What The Study Did: Researchers compared the likelihood of delayed childbearing among physicians and nonphysicians.

Authors: Andrea N. Simpson, M.D., of the University of Toronto, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2021.1635)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

BURLINGTON, VT -- In the aftermath of George Floyd's 2020 murder by former police officer Derek Chauvin, many families may find themselves actively engaging in--or uncomfortably fumbling around--discussions about race. For white parents looking to clearly communicate antiracist ideologies with their preadolescent children, a new study offers some insight.

"There's a difference between saying race "shouldn't" matter and race "doesn't" matter," explains Jamie Abaied, professor of developmental psychology at the University of Vermont and lead author of the study, co-authored by Sylvia Perry, a professor of psychology at Northwestern University. Though "shouldn't" and "doesn't" may seem similar, the study reveals just how different they can be.

Released online by the journal Cultural Diversity and Ethnic Minority Psychology on Monday, the study analyzes data collected in summer 2015 (in the weeks immediately following the Charleston church shooting) from a sample of white American parents responding to questions about how they talk about race with their children, ages 8-12. It aims to understand whether or not white American parents communicate contradictory messages about race to their children; and if so, how and why?

The short answer: Yes, they do--but probably unintentionally. The study found that more than a third of parents communicated mixed messages about race, whereas the remaining two-thirds either communicated consistent ideas about their racial ideology or simply communicated no ideas about race at all. "Before we really develop specific interventions to help parents talk to their kids about race, we need to know what they're currently saying to their kids and how they're currently thinking about these discussions," she says. Until now, there hasn't been much research on that, particularly among parents of children older than age 7.

"When parents offered mixed messages about race, they were saying really positive things like, 'Racism is real and it's wrong,' but they were also saying that race isn't that important, or that 'It's only skin deep,' which is a type of thinking that researchers call colorblindness," she explains. About half the parents endorsed colorblindness at least once in their responses, and more than twenty-one percent of parents in the study only communicated colorblind thinking to their children.

Though not the focus of the study, these findings add to an existing body of psychological research that recalibrates the scales from simply "racist" or "not racist," to "racist" or "counteractive to racist." It's a concept known as antiracism, and it significantly impacts today's understanding of racial colorblindness.

The study describes colorblindness as "a modern form of racism, which can take the form of either color-evasion (claiming to 'not see' race) or power evasion (denying that racial inequality is a reality)." It can downplay race, imply that it isn't important, or divert awareness. And according to Abaied, it's the most problematic takeaway from the study.

"The problem with colorblindness is that race is real. It has real effects on people's lived experiences. If you don't think race is real, it makes it easier to go a step further and believe that racism isn't real," Abaied says. "I think some of the parents were well-meaning and trying to voice egalitarian beliefs, such as, 'I believe people of different races should be treated equally,' which is different from, 'I don't see color, everybody's equal.' In doing that, they are implying that race doesn't matter. The difference is very nuanced, but also very important."

"Colorblindness is not a pathway to racial equality," she adds. "There's a false belief that if we just stop talking about race, everything will be fine." In fact, Abaied found that most white parents, sixty-three percent, reported that they didn't discuss race-related news with their children at the time, which included the killings of Trayvon Martin, Michael Brown and Freddie Gray in addition to the 2015 Charleston church shooting.

Reasons for that ranged from parents wanting to shield their children from difficult topics--"No, a child should not be told about death and murder. Those are adult topics," one parent said--to perceptions of relevance--"I have not. Why would I bring that up?" stated another.

"The results indicate that white parents have the potential to be agents of change that socialize color conscious beliefs in their children, but many are reinforcing the current system of colorblind indifference to racial inequality," the study explains.

However, the researchers also found that nearly thirty-four percent of participants exclusively communicated in color conscious ideologies, which directly challenge colorblindness. In practice, that looks like white parents "celebrating racial diversity rather than minimizing it, openly acknowledging rather than denying the impact of race on people's lives through discrimination and structural racism, and advocating for equal rights and treatment across different racial groups," the study explains.

Many parents voiced this belief in response to a hypothetical question that asked what they would say to their child if they encountered an incident of race-related prejudice together. Roughly half the parents endorsed the idea that people should receive equal treatment, regardless of race. "I would tell her that what she witnessed was wrong and only hurtful people act like that and we should accept everyone as equals," one parent stated.

However, another parent stated: "I would tell her that everybody is different and the color of your skin is no reason to treat anyone any differently." Both parents endorse equal treatment regardless of race, but differ on how they define the incident itself as "wrong" to their children--only the former explicitly mentioned race in their answer.

Abaied sees the study as a first step toward developmental trainings and programs designed to help guide parents--or possibly even teachers--through these messaging nuances and straight into constructive, intentional conversations about race. "Kids' ideas about race start to solidify in adolescence, so it's not too late to have these conversations during the elementary school years. I think it would be good for parents to talk about this early," she says.

Though family conversations are just one piece of the puzzle to be solved, Abaied points out by engaging multiple generations through one conversation, those conversations have potential to be highly impactful.

Follow-up research to the study is currently underway, with Abaied and her team analyzing a new data set for the study collected in 2020 (after the murder of George Floyd) that will enable them to track and compare progress over time.

Talking about your bad day at work could lead to great solutions. Cold Spring Harbor Laboratory (CSHL) Associate Professor Saket Navlakha and his wife, Dr. Sejal Morjaria, an infectious disease physician at Memorial Sloan Kettering Cancer Center (MSK), found a way to predict COVID-19 severity in cancer patients. The computational tool they developed prevents unnecessary expensive testing and improves patient care.

Morjaria says, "Generally, I have good intuition for how patients will progress." However, that intuition failed her when confronted with COVID-19. She says:

"When the pandemic first hit, we had a hard time understanding and predicting which patients were going to have severe COVID. People were ordering a slew of labs, and a lot of times, there were unnecessary lab tests."

Navlakha joined CSHL in 2019. He uses computer science to understand biological processes. Morjaria wondered if her husband could help:

"So I came home and I would tell him, 'Saket, it would be great if we could come up with a methodology to figure out, using machine-learning, which patients are going to go on to develop severe COVID versus not.'"

The team collected 267 variables from cancer patients diagnosed with COVID-19. The variables ranged from age and sex to cancer type, most recent treatments, and laboratory results. They trained a machine-learning computer program to classify patients into three groups. Those who will require high levels of oxygen through a ventilator:

immediately

after a few days

not at all

The researchers found approximately 50 variables that contributed most to the outcome prediction. Their method had an accuracy rate of 70-85%, and it performed especially well for patients that would require immediate ventilation. More generally, the tool can help tease apart interactions between multiple risk factors that might not be apparent, even to those with trained eyes. The program also prevents over-testing, which Morjaria knows will "spare patients unnecessary massive hospital costs."

Navlakha believes this work would not have been possible without close collaboration with his wife and other MSK clinician-scientists, including Rocio-Perez Johnston and Ying Taur. He says:

"Sejal and I talk about better ways to integrate what she's experiencing on the bedside versus what we can analyze and do computationally. As someone who's never worked with clinical data, if I were to try to have done this without Sejal's guidance, I would have made tons of mistakes, it would have just been a total disaster and totally unusable."

Navlakha and Morjaria hope their work will inspire more physicians and computer scientists to work together and create innovative clinical solutions for complex diseases.

A Wyss Institute-led collaboration spanning four research labs and hundreds of miles has used the Institute's organ-on-a-chip (Organ Chip) technology to identify the antimalarial drug amodiaquine as a potent inhibitor of infection with SARS-CoV-2, the virus that causes COVID-19.

The Organ Chip-based drug testing ecosystem established by the collaboration greatly streamlines the process of evaluating the safety and efficacy of existing drugs for new medical applications, and provides a proof-of-concept for the use of Organ Chips to rapidly repurpose existing drugs for new medical applications, including future pandemics. The research is reported in Nature Biomedical Engineering.

While many groups around the world have been testing existing drugs for efficacy against COVID-19 using cultured cells, it is well known that cells grown in a dish do not behave like the cells in a living human body, and many drugs that appear effective in lab studies do not work in patients. The Wyss team examined eight existing drugs, including hydroxychloroquine and chloroquine, that they and others had found were active against SARS-CoV-2 in conventional cell culture assays.

When tested in their more sophisticated microfluidic Lung Airway Chip, which had been infected with a pseudotyped SARS-CoV-2 virus, they found that most of these drugs, including hydroxychloroquine and chloroquine, were not effective. However, another antimalarial drug, amodiaquine, was highly effective at preventing viral entry. These results were then validated in cultured cells and in a small animal model of COVID-19 using infectious SARS-CoV-2 virus. Amodiaquine is now in clinical trials for COVID-19 at multiple sites in Africa, where this drug is inexpensive and widely available.

"The speed with which this team assembled, pivoted to COVID-19, and produced clinically significant results is astonishing," said senior author and Wyss Institute Founding Director Don Ingber, M.D., Ph.D. "We started testing these compounds in February 2020, had data by March, and published a preprint in April. Thanks to the openness and collaboration that the pandemic has sparked within the scientific community, our lead drug is now being tested in humans. It's a powerful testament to Organ Chips' ability to accelerate preclinical testing."

From mysterious disease to lead compound in months

In the early months of the COVID-19 pandemic when little was known about the novel SARS-CoV-2 virus, efforts were made around the globe to identify existing drugs that could be repurposed to treat patients who were falling ill. While early data performed on cells grown in lab dishes seemed to suggest that the antimalarial drugs chloroquine and hydroxychloroquine could treat the disease, later studies showed that they aren't active against SARS-CoV-2 in animals or patients, and the quest for an effective oral therapeutic that can both treat and prevent COVID-19 continues.

Fortunately, the Wyss Institute had a ready-made solution to that problem. In a move that today seems prescient, over three years ago the Defense Advanced Research Projects Agency (DARPA) and National Institutes of Health (NIH) awarded funding to Ingber's team to explore whether its human Organ Chip microfluidic culture technology, which faithfully mimics the function of human organs in vitro, could be used to confront potential biothreat challenges including pandemic respiratory viruses.

Two years into the project, the team was making steady progress using its lung Airway Chip to study drugs that could be repurposed to treat influenza virus infections. Then, in January 2020, first authors Longlong Si, Ph.D. and Haiqing Bai, Ph.D. heard about cases of what was being called a novel viral pneumonia in China.

"That caught a lot of scientists' attention, because any new virus could become a global threat given how easily infections spread in today's era of widespread international travel. We closely followed the updates because we thought that our Airway Chip model could provide an important tool for studying this virus," said Si, a Wyss Technology Development Fellow and co-lead author. Once it became clear that people were falling ill due to the mysterious COVID-19 and not pneumonia, the team quickly shifted its focus to the novel SARS-CoV-2 virus.

The human Airway Chip that the Wyss team developed for these studies is a microfluidic device about the size of a USB memory stick that contains two parallel channels separated by a porous membrane. Human lung airway cells are grown in one channel that is perfused with air, while human blood vessel cells are grown in the other channel, which is perfused with liquid culture medium to mimic blood flow. Cells grown in this device naturally differentiate into multiple airway-specific cell types in proportions that are similar to those in the human airway, and develop traits observed in living lungs such as cilia and the ability to produce and move mucus. Airway Chip cells also have higher levels of angiotensin-converting enzyme-2 (ACE2) receptor protein, which plays a central role in lung physiology and is used by SARS-CoV-2 to infect cells.

"Our biggest challenge in shifting our focus to SARS-CoV-2 was that we don't have lab facilities with the necessary infrastructure to safely study dangerous pathogens. To get around that problem, we designed a SARS-CoV-2 pseudovirus that expresses the SARS-CoV-2 spike protein, so that we could identify drugs that interfere with the spike protein's ability to bind to human lung cells' ACE2 receptors," said Bai, who is a Postdoctoral Fellow at the Wyss Institute and co-lead author. "A secondary goal was to demonstrate that these types of studies could be carried out by other Organ Chip researchers who similarly have this technology, but lack access to lab facilities required to study highly infectious viruses."

Armed with the pseudovirus that allowed them to study SARS-CoV-2 infection, the team first perfused the Airway Chips' blood vessel channel with several approved drugs, including amodiaquine, toremifene, clomiphene, chloroquine, hydroxychloroquine, arbidol, verapamil, and amiodarone, all of which have exhibited activity against other related viruses in previous studies. However, in contrast to static culture studies, they were able to perfuse the drug through the channels of the chip using a clinically relevant dose to mimic how the drug would be distributed to tissues in our bodies. After 24 hours they introduced SARS-CoV-2 pseudovirus into the Airway Chips' air channel to mimic infection by airborne viruses, like that in a cough or sneeze.

Only three of these drugs ? amodiaquine, toremifene, and clomiphene ? significantly prevented viral entry without producing cell damage in the Airway Chips. The most potent drug, amodiaquine, reduced infection by about 60%. The team also performed spectrometry measurements with the assistance of Steve Gygi, Ph.D.'s group at Harvard Medical School to assess how the drugs impacted the airway cells. These studies revealed that amodiaquine produced distinct and broader protein changes than the other antimalarial drugs.

The researchers had a lead drug candidate.

All hands on deck

Despite the promise of amodiaquine, the team still needed to demonstrate that it worked against the real infectious SARS-CoV-2 virus. With the help of a new COVID-19-focused grant from DARPA, Ingber teamed up with Matthew Frieman, Ph.D. at the University of Maryland School of Medicin and Benjamin tenOever, Ph.D. at the Icahn School of Medicine at Mount Sinai, both of whom already had biosafety labs set up to study infectious pathogens.

This collaboration created a drug discovery ecosystem that combines the human emulation capability of the Wyss Institute's Organ Chips with Frieman's and tenOever's expertise in the interactions between viruses and their host cells. The Frieman lab tested amodiaquine and its active metabolite, desethylamodiaquine, against native SARS-CoV-2 via high-throughput assays in cells in vitro, and confirmed that the drug inhibited viral infection.

In parallel, the tenOever lab tested amodiaquine and hydroxychloroquine against native SARS-CoV-2 in a head-to-head comparison in a small animal COVID-19 model, and saw that prophylactic treatment with amodiaquine resulted in ~70% reduction in viral load upon exposure, while hydroxychloroquine was ineffective. They also saw that amodiaquine prevented the transmission of the virus from sick to healthy animals more than 90% of the time, and that it was also effective in reducing viral load when administered after introduction of the virus. Thus, their results suggest that amodiaquine could work in both treatment and prevention modes.

"Seeing how beautifully amodiaquine inhibited infection in the Airway Chip was extremely exciting," said Frieman. "And, the fact that it seems to work both before and after exposure to SARS-CoV-2 means that it could potentially be effective in a wide variety of settings."

"This collaboration has allowed us to do things that we never would have had the resources to do otherwise, including recently setting up Organ Chips in our own lab so that we can now use them to study the interactions between infectious viruses and their hosts. While we're proud of what we've accomplished so far for COVID-19, we're also looking forward to studying additional virus-host dynamics using the Organ Chips in the hopes that we'll be able to prevent or address future pandemics," said tenOever, who is a Professor of Microbiology.

A preprint of the amodiaquine results was published online on April 15, 2020, which generated buzz in the scientific community. It eventually caught the eye of Medicines for Malaria Venture, a leading product development partnership in antimalarial drug research. These results, along with studies from several other groups, contributed to amodiaquine's inclusion in a clinical trial in collaboration with the University of Witwatersrand in South Africa and Shin Poong Pharmaceutical in South Korea last fall. A few months later, the Drugs for Neglected Diseases Initiative (DNDi) added amodiaquine to the ANTICOV clinical trial for COVID-19, which spans 19 sites in over 13 different countries in Africa. Amodiaquine is oral, extremely inexpensive, and widely available in Africa. If proven effective in these clinical trials, it could provide a badly needed weapon against COVID-19 in low-resource nations where access to vaccines and expensive new therapeutics is limited.

Preparing for the next pandemic

While the identification of amodiaquine is a major boon in fighting COVID-19, the team already has their sights set on future pandemics. In addition to SARS-CoV-2, their recent publication details their success in finding drugs that could protect against or treat several strains of influenza virus.

"Thanks to our experience using this drug development pipeline to validate amodiaquine for COVID-19, we are now applying what we learned to influenza and other pandemic-causing pathogens," said co-author Ken Carlson, Ph.D., a Lead Senior Staff Scientist who helps lead the Coronavirus Therapeutic Project Team at the Wyss Institute. "This process has given us confidence that Organ Chips are predictive of what we see in more complex living models of viral infections, and helped harness the creative cauldron of the Wyss Institute to consolidate and strengthen our therapeutic discovery engine."

In addition to influenza, the team is now exploring drugs that could be used against the new SARS-CoV-2 mutant strains, to suppress the dangerous "cytokine storm" that leads to many hospitalizations, and to relieve the symptoms of COVID-19 "long haulers."

"The pandemic has really gelled the Wyss Institute's Bioinspired Therapeutics development program, and linking up with the Frieman and tenOever labs has created a drug discovery and development pipeline that dramatically speeds up the whole process, quickly shepherding COVID-19 drugs through preclinical development to the point where they can be tested in humans. With Organ Chip technology in hand, we are now in a stronger position to confront future pandemics," said Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.