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A new study by Texas A&M University researchers published in PLOS ONE details a new model for making short-term projections of daily COVID-19 cases that is accurate, reliable and easily used by public health officials and other organizations.
Led by Hongwei Zhao, professor of biostatistics at the Texas A&M School of Public Health, researchers used a method based on the SEIR (susceptible, exposed, infected and recovered states) framework to project COVID-19 incidence in the upcoming two to three weeks based on observed incidence cases only. This model assumes a constant or small change in the transmission rate of the virus that causes COVID-19 over a short period.
The model uses publicly available data on new reported cases of COVID-19 in Texas from the COVID-19 Data Repository by the Center for Systems Science and Engineering at Johns Hopkins University. Texas A&M researchers used this data on disease incidence for Texas and a selection of counties that included the Texas A&M campus to estimate the COVID-19 transmission rate.
“The results indicate that this model can be used to reasonably predict COVID-19 cases two to three weeks in advance using only current incidence numbers,” Zhao said. “The simplicity of this model is one of its greatest strengths as it can be easily implemented by organizations with few resources. Forecasts from this model can help health care organizations prepare for surges and help public health officials determine whether mask mandates or other policies will be needed.”
They forecasted future infections under three possible scenarios: a sustained, constant rate of transmission; one where the transmission rate is five percent higher than current levels, reflecting a decrease in practices to prevent transmission or an increase in conditions that promote transmission; and one where transmission is five percent lower.
Estimating the current effective transmission rate can be tricky, since day-to-day variations in both infections and reporting can dramatically influence this estimate. Thus, the researchers smoothed daily reporting variations using a three-day weighted average and performed additional smoothing to account for data anomalies such as counties reporting several months of cases all at once.
The researchers compared their projections with reported incidence in Texas through four periods in 2020: April 15, June 15, August 15 and October 15. The number of new daily COVID-19 cases reported were relatively low in mid-April, when many businesses were shut down, and then started to increase in early May after phased re-openings began in Texas. The numbers increased sharply after Memorial Day, and then trended downward after a statewide mask mandate was enacted during the summer. Infections increased again after Labor Day, but then seemed to plateau until the middle of October, when the transmission rate was observed again to increase dramatically.
The statewide application of the model showed that it performed reasonably well, with only the second period forecast deviating from the actual recorded incidence, perhaps due to the dramatically changing numbers at the time when a great wave of COVID-19 occurred around the Memorial Day holiday. The model performed similarly well at the county level, though the smaller population and changes in population, such as students moving in and out of the area during the school year, influenced reporting of new cases.
However, the model is limited by the data it uses. Local testing and reporting policies and resources can affect data accuracy, and assumptions about transmission rate based on current incidence are less likely to be accurate further into the future. And as more people contract COVID-19 and recover, or are vaccinated, the susceptible population will change, possibly affecting transmission.
Despite these limitations, the researchers said the model can be a valuable tool for health care facilities and public health officials, especially when combined with other sources of information. The COVID-19 pandemic is not yet over, so having a tool that can determine when and where another surge might occur is important. Similarly, researchers hope to use these new tools at their disposal for future infectious disease needs.
Additionally, the model has been used to create a dashboard that provides real-time data on the spread of COVID-19 state-wide. It has been used locally by university administrators and public health officials.
Other School of Public health researchers involved in this study included Marcia Ory, Tiffany Radcliff, Murray Côté, Rebecca Fischer and Alyssa McNulty, along with Department of Statistics researchers Huiyan Sangand and Naveed Merchant.
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Materials provided by Texas A&M University. Original written by Rae Lynn Mitchell. Note: Content may be edited for style and length.

Financial stress can have an immediate impact on well-being, but can it lead to physical pain nearly 30 years later? The answer is yes, according to new research from University of Georgia scientists.
The study, published in Stress & Health, reveals that family financial stress in midlife is associated with a depleted sense of control, which is related to increased physical pain in later years.
“Physical pain is considered an illness on its own with three major components: biological, psychological and social,” said Kandauda A.S. Wickrama, first author and professor in the College of Family and Consumer Sciences. “In older adults, it co-occurs with other health problems like limited physical functioning, loneliness and cardiovascular disease.”
Most pain research is neurological, but it’s important to also connect it to stressful family experiences, according to the researchers.
“Dr. Wickrama and I are both interested in the context surrounding families and how that context impacts the relational, physical and mental health of the individuals in the family,” said lead author Catherine Walker O’Neal, associate research scientist in the College of Family and Consumer Sciences. “Finances are an important component of our work because it’s such a relevant contextual stressor families face.”
The authors used data from the Iowa Youth and Family Project, a longitudinal study that provides 27 years of data on rural families from a cluster of eight counties in north-central Iowa. The data was collected in real time from husbands and wives in 500 families who experienced financial problems associated with the late 1980s farm crisis. Most of the individuals are now over 65 years old, and the couples are in enduring marriages — some as long as 45 years.
Even after the researchers controlled for concurrent physical illnesses, family income and age, they found a connection between family financial hardship in the early 1990s and physical pain nearly three decades later. Additional findings from their study show it’s more likely that financial strain influences physical pain, though physical pain can in turn influence financial strain through additional health care costs.
Physical pain is a biopsychosocial phenomenon, according to Wickrama. The research suggests that stressful experiences like financial strain erode psychological resources like a sense of control. This depletion of resources activates brain regions that are sensitive to stress, launching pathological, physiological and neurological processes that lead to health conditions like physical pain, physical limitations, loneliness and cardiovascular disease.
“In their later years, many complain about memory loss, bodily pain and lack of social connections,” he said. “Nearly two-thirds of adults complain of some type of bodily pain, and nearly that many complain of loneliness. That percentage is going up, and the health cost for that is going up. That is a public health concern.”
Eric T. Klopack, who recently graduated from UGA and is currently a postdoctoral fellow at University of Southern California, is also co-author on this paper.
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Materials provided by University of Georgia. Original written by Allyson Mann. Note: Content may be edited for style and length.

SharecloseShare pageCopy linkAbout sharingimage copyrightWeizhi Ji/Kunming Univ of Science and TechnologyMonkey embryos containing human cells have been made in a laboratory, a study has confirmed.The research, by a US-Chinese team, has sparked fresh debate into the ethics of such experiments. The scientists injected human stem cells – cells that have the ability to develop into many different body tissues – into macaque embryos.The developing embryos were studied for up to 20 days.Other so-called mixed-species embryos, or chimeras, have been produced in the past, with human cells implanted into sheep and pig embryos.The scientists were led by Prof Juan Carlos Izpisua Belmonte of the Salk Institute in the US, who, in 2017, helped make the first human-pig hybrid.Human-pig ‘chimera embryos’ detailedFirst ‘mixed embryo’ monkeys bornTheir work could pave the way in addressing the severe shortage in transplantable organs as well as help understand more about early human development, disease progression and ageing, he said. “These chimeric approaches could be really very useful for advancing biomedical research not just at the very earliest stage of life, but also the latest stage of life.”He maintained that the study, published in the journal Cell, had met the current ethical and legal guidelines.”Ultimately, we conduct these studies to understand and improve human health,” he said.’Ethical challenges’Some scientists have, however, raised concerns about the experiment, arguing that while the embryos in this case were destroyed at 20 days, others could try to take the work further. They are calling for public debate over the implications of creating part human/part nonhuman chimeras.Commenting on the research, Dr Anna Smajdor, lecturer and researcher in biomedical ethics at the University of East Anglia’s Norwich Medical School, said it posed “significant ethical and legal challenges”.She added: “The scientists behind this research state that these chimeric embryos offer new opportunities, because ‘we are unable to conduct certain types of experiments in humans’. But whether these embryos are human or not is open to question.”Prof Julian Savulescu, director of the Oxford Uehiro Centre for Practical Ethics and co-director of the Wellcome Centre for Ethics and Humanities, University of Oxford, said the research “opens Pandora’s box to human-nonhuman chimeras”.He added: “These embryos were destroyed at 20 days of development but it is only a matter of time before human-nonhuman chimeras are successfully developed, perhaps as a source of organs for humans. That is one of the long-term goals of this research.”Sarah Norcross, director of the Progress Educational Trust, said that while “substantial advances” are being made in embryo and stem cell research, which could bring equally substantial benefits, “there is a clear need for public discussion and debate about the ethical and regulatory challenges raised”. Follow Helen on Twitter.

Vaccines do a good job of protecting us from coronavirus, but fear and confusion about the rise of variants have muddled the message. Here are answers to common questions.The news about coronavirus variants can sound like a horror movie, with references to a “double-mutant” virus, “vaccine-evading” variants and even an “Eek” mutation. One headline warned ominously: “The devil is already here.”While it’s true that the virus variants are a significant public health concern, the unrelenting focus on each new variant has created undue alarm and a false impression that vaccines don’t protect us against the various variants that continue to emerge.“I use the term ‘scariants,’” said Dr. Eric Topol, professor of molecular medicine at Scripps Research in La Jolla, Calif., referring to much of the media coverage of the variants. “Even my wife was saying, ‘What about this double mutant?’ It drives me nuts. People are scared unnecessarily. If you’re fully vaccinated, two weeks post dose, you shouldn’t have to worry about variants at all.”Viruses are constantly changing, and new variants have been emerging and circulating around the world throughout the pandemic. Some mutations don’t matter, but others can make things much worse by creating a variant that spreads faster or makes people sicker. While the rise of more infectious variants has caused cases of Covid-19 to surge around the world, the risk is primarily to the unvaccinated, for whom there is great concern. While vaccination efforts are well underway in the United States and many other developed countries, huge swaths of the world’s population remain vulnerable, with some countries yet to report having administered a single dose.But for the vaccinated, the outlook is much more hopeful. While it’s true that the vaccines have different success rates against different variants, the perception that they don’t work against variants at all is incorrect. In fact, the available vaccines have worked remarkably well so far, not just at preventing infection but, most important, at preventing serious illness and hospitalization, even as new variants circulate around the globe.The variants are “all the more reason to get vaccinated,” said Dr. Anthony S. Fauci, the nation’s top infectious disease specialist. “The bottom line is the vaccines we are using very well protect against the most dominant variant we have right now, and to varying degrees protect against serious disease among several of the other variants.”Part of the confusion stems from what vaccine efficacy really means and the use of terms like “vaccine evasion,” which sounds a lot scarier than it is. In addition, the fact that two vaccines have achieved about 95 percent efficacy has created unrealistic expectations about what it takes for a vaccine to perform well. Here are answers to common questions about the variants and the vaccines being used to stop Covid-19.Which variant am I most likely to encounter in the United States?The variant called B.1.1.7, which was first identified in Britain, is now the most common source of new infections in the United States. This highly contagious variant is also fueling the spread of the virus in Europe and has been found in 114 countries. A mutation allows this version of the virus to more effectively attach to cells. Carriers may also shed much higher levels of virus and stay infectious longer.The main concern about B.1.1.7 is that it is highly infectious and spreads quickly among the unvaccinated, potentially overwhelming hospitals in areas where cases are surging.Do the vaccines work against B.1.1.7?All of the major vaccines in use — Pfizer-BioNTech, Moderna, Johnson & Johnson, AstraZeneca, Sputnik and Novavax — have been shown to be effective against B.1.1.7. We know this from a variety of studies and indicators. First, scientists have used the blood of vaccinated patients to study how well vaccine antibodies bind to a variant in a test tube. The vaccines have all performed relatively well against B.1.1.7. There’s also clinical trial data, particularly from Johnson & Johnson and AstraZeneca (which is the most widely used vaccine around the world), that shows they are highly effective against both preventing infection and serious illness in areas where B.1.1.7 is circulating. And in Israel, for instance, where 80 percent of the eligible population is vaccinated (all with the Pfizer shot), case counts are plummeting, even as schools, restaurants and workplaces open up, suggesting that vaccines are tamping down new infections, including those caused by variants.If the vaccines are working, why do I keep hearing about “breakthrough” cases?No vaccine is foolproof, and even though the Covid vaccines are highly protective, sometimes vaccinated people still get infected. But breakthrough cases of vaccinated people are very rare, even as variants are fueling a surge in case counts. And the vaccines clearly prevent severe illness and hospitalization in the few vaccinated patients who do get infected.So what’s the risk of getting infected after vaccination? Nobody knows for sure, but we have some clues. During the Moderna trial, for instance, only 11 patients out of 15,210 who were vaccinated got infected. Both Pfizer and Moderna now are doing more detailed studies of breakthrough cases among vaccinated trial participants, and should be releasing that data soon.Two real-world studies of vaccinated health care workers, who have a much higher risk of virus exposure than the rest of us, offer hopeful signs. One study found that just four out of 8,121 fully vaccinated employees at the University of Texas Southwestern Medical Center in Dallas became infected. The other found that only seven out of 14,990 workers at UC San Diego Health and the David Geffen School of Medicine at the University of California, Los Angeles, tested positive two or more weeks after receiving a second dose of either the Pfizer-BioNTech or Moderna vaccines. Both reports were published in the New England Journal of Medicine, and are a sign that even as cases were surging in the United States, breakthrough cases were uncommon, even among individuals who were often exposed to sick patients. Most important, patients who were infected after vaccination had mild symptoms. Some people had no symptoms at all, and were discovered only through testing in studies or as part of their unrelated medical care.Researchers are still studying whether the variants eventually might increase the number of breakthrough cases or if vaccine antibodies begin to wane over time. So far, data from Moderna show the vaccine still remains 90 percent effective after at least six months. Pfizer has reported similar results. A recent study of 149 people in Israel who became infected after vaccination with the Pfizer vaccine suggested that a variant first identified in South Africa was more likely to cause breakthrough infections. However, those eight infections occurred between days seven and 13 following the second dose. “We didn’t see any South Africa variant 14 days after the second dose,” said Adi Stern, the study’s senior author, a professor at the Shmunis School of Biomedicine and Cancer Research, Tel Aviv University. “It was a small sample size, but it’s very possible that two weeks after the second dose, maybe the protection level goes up and that blocks the South Africa variant completely. It gives us more room for optimism.”For now, the variants don’t appear to be increasing the rate of infection in vaccinated people, but that could change as more data are collected. Read more about breakthrough cases here.Are there other variants we should be worried about?The C.D.C. is tracking more than a dozen variants, but only a few qualify as “variants of concern,” which is a public health designation to identify variants that could be more transmissible or have other qualities that make them more of a risk. The main additional variants everyone is talking about right now are the B.1.351, which was first detected in South Africa, and the P.1, which was first identified in Brazil. While there are other variants (including two “California” variants, B.1.427 and B.1.429, and a New York variant, B.1.526) for now, it seems, that the South Africa and Brazil variants (which as of late March together accounted for about 2 percent of cases in the United States) are causing the most concern. While a new variant can emerge at any time, existing variants also compete with each other for dominance. One interesting new development: In countries like the United States where B.1.1.7 is dominant, some of the other variants seem to be getting crowded out, making them less of a worry.Is it true that the variants first identified in South Africa and Brazil can “evade” the vaccines?There is a concern that the B.1.351 and the P.1 are better at dodging vaccine antibodies than other variants. But that doesn’t mean the vaccines don’t work at all. It just means the level of protection you get from the vaccines against these variants could be lower than when the shots were studied against early forms of the virus. Among the variants, the B.1.351 may pose the biggest challenge so far. It has a key mutation — called E484K, and often shortened to “Eek” — that can help the virus evade some, but probably not all, antibodies.Remember that there’s a lot of “cushion” provided by this current crop of vaccines, so even if a vaccine is less effective against a variant, it appears that it’s still going to do a good job of protecting you from serious illness.How much protection will the vaccines give me against the variant first seen in South Africa?We don’t yet have precise estimates of vaccine effectiveness against B.1.351, which may be the most challenging variant so far. But studies show that the various vaccines still lower overall risk for infection and help prevent severe disease. A large study of Johnson & Johnson’s one-dose vaccine in South Africa found it was about 85 percent effective at preventing severe disease, and lowered risk for mild to moderate disease by 64 percent. (Distribution of the Johnson & Johnson vaccine has been paused as health officials investigate safety concerns.) There’s less definitive research for the Pfizer and Moderna vaccines against the variant, but it’s believed that these two-dose vaccines still reduce risk of infection against the variant by about 60 percent to 70 percent and still are highly effective at preventing severe disease and hospitalization..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-rqynmc{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.9375rem;line-height:1.25rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-rqynmc{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-rqynmc strong{font-weight:600;}.css-rqynmc em{font-style:italic;}.css-yoay6m{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}@media (min-width:740px){.css-yoay6m{font-size:1.25rem;line-height:1.4375rem;}}.css-1dg6kl4{margin-top:5px;margin-bottom:15px;}.css-16ed7iq{width:100%;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-webkit-justify-content:center;-ms-flex-pack:center;justify-content:center;padding:10px 0;background-color:white;}.css-pmm6ed{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}.css-pmm6ed > :not(:first-child){margin-left:5px;}.css-5gimkt{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.8125rem;font-weight:700;-webkit-letter-spacing:0.03em;-moz-letter-spacing:0.03em;-ms-letter-spacing:0.03em;letter-spacing:0.03em;text-transform:uppercase;color:#333;}.css-5gimkt:after{content:’Collapse’;}.css-rdoyk0{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-eb027h{max-height:5000px;-webkit-transition:max-height 0.5s ease;transition:max-height 0.5s ease;}.css-6mllg9{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;position:relative;opacity:0;}.css-6mllg9:before{content:”;background-image:linear-gradient(180deg,transparent,#ffffff);background-image:-webkit-linear-gradient(270deg,rgba(255,255,255,0),#ffffff);height:80px;width:100%;position:absolute;bottom:0px;pointer-events:none;}#masthead-bar-one{display:none;}#masthead-bar-one{display:none;}.css-1pd7fgo{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-1pd7fgo{padding:20px;width:100%;}}.css-1pd7fgo:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1pd7fgo{border:none;padding:20px 0 0;border-top:1px solid #121212;}.css-1pd7fgo[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-1pd7fgo[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-1pd7fgo[data-truncated] .css-5gimkt:after{content:’See more’;}.css-1pd7fgo[data-truncated] .css-6mllg9{opacity:1;}.css-1rh1sk1{margin:0 auto;overflow:hidden;}.css-1rh1sk1 strong{font-weight:700;}.css-1rh1sk1 em{font-style:italic;}.css-1rh1sk1 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#ccd9e3;text-decoration-color:#ccd9e3;}.css-1rh1sk1 a:visited{color:#333;-webkit-text-decoration-color:#ccc;text-decoration-color:#ccc;}.css-1rh1sk1 a:hover{-webkit-text-decoration:none;text-decoration:none;}“From everything we know today, there is still protection from the vaccines against the South Africa variant,” said Dr. Stern.Should I still worry that the vaccines are less effective against some variants?Part of the problem is that we misinterpret what efficacy really means. When someone hears the term “70 percent efficacy,” for instance, they might wrongly conclude that it means 30 percent of vaccinated people would get sick. That’s not the case. Even if a vaccine loses some ground to a variant, a large portion of people are still protected, and only a fraction of vaccinated people will get infected. Here’s why.To understand efficacy, consider the data from the Pfizer clinical trials. In the unvaccinated group of 21,728, a total of 162 people got infected. But in the vaccinated group of 21,720, only eight people became infected. That’s what is referred to as 95 percent efficacy. It doesn’t mean that 5 percent of the participants (or 1,086 of them) got sick. It means 95 percent fewer vaccinated people got infected compared to the unvaccinated group.Now imagine a hypothetical scenario with a vaccine that is 70 percent effective against a more challenging variant. Under the same conditions of the clinical trial, vaccination would still protect 21,672 people in the group, and just 48 vaccinated people — less than one percent — would become infected, compared to 162 in the unvaccinated group. Even though overall efficacy was lower, only a fraction of vaccinated people in this scenario would get infected, most likely with only mild illness.While far more research is needed to fully understand how variants might dodge some (but not all) vaccine antibodies, public health experts note that an estimate of 50 percent to 70 percent efficacy against a challenging variant would still be considered an adequate level of protection.“Seventy percent is extremely high,” said Dr. Stern. “Basically what this means is that it’s even more important to get vaccinated. If you have 95 percent efficacy, you can create some form of herd immunity with less people. With 70 percent efficacy, it’s even more important to get vaccinated to protect others.”Am I going to need a booster shot?Vaccine makers already are working on developing booster shots that will target the variants, but it’s not clear how soon they might be needed. “In time, you’re going to see a recommendation for a booster,” said Dr. Peter J. Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston. “That booster will elevate everybody’s antibodies and increase durability. The booster will probably be configured to target the South African and Brazil variants.”Given all these unknowns about the variants, shouldn’t I just stay home even after I’m vaccinated?Even amid the rise of variants, vaccines will significantly lower your risk for infection and will protect you from serious illness and hospitalization.People who are vaccinated can socialize, unmasked, with other vaccinated people. While vaccinated people still need to follow local health guidelines about wearing a mask and gathering in groups to protect the unvaccinated, vaccinated people can travel, get their hair and nails done, or go to work without worrying. And vaccinated grandparents can hug their unvaccinated grandchildren. Because there are still some outstanding questions about the risk of vaccinated people carrying the virus, a vaccinated person is still advised to wear a mask in public to protect the unvaccinated — although those guidelines may be updated soon.“The vaccines protect you, so go get vaccinated — that’s the message,” said Dr. Fauci. “If you’re around other vaccinated people, you shouldn’t worry about it at all. Zero.”

Investigators in China and the United States have injected human stem cells into primate embryos and were able to grow chimeric embryos for a significant period of time — up to 20 days. The research, despite its ethical concerns, has the potential to provide new insights into developmental biology and evolution. It also has implications for developing new models of human biology and disease. The work appears April 15 in the journal Cell.
“As we are unable to conduct certain types of experiments in humans, it is essential that we have better models to more accurately study and understand human biology and disease,” says senior author Juan Carlos Izpisua Belmonte, a professor in the Gene Expression Laboratory at the Salk Institute for Biological Sciences. “An important goal of experimental biology is the development of model systems that allow for the study of human diseases under in vivo conditions.”
Interspecies chimeras in mammals have been made since the 1970s, when they were generated in rodents and used to study early developmental processes. The advance that made the current study possible came last year when this study’s collaborating team — led by Weizhi Ji of Kunming University of Science and Technology in Yunnan, China — generated technology that allowed monkey embryos to stay alive and grow outside the body for an extended period of time.
In the current study, six days after the monkey embryos had been created, each one was injected with 25 human cells. The cells were from an induced pluripotent cell line known as extended pluripotent stem cells, which have the potential to contribute to both embryonic and extra-embryonic tissues. After one day, human cells were detected in 132 embryos. After 10 days, 103 of the chimeric embryos were still developing. Survival soon began declining, and by day 19, only three chimeras were still alive. Importantly, though, the percentage of human cells in the embryos remained high throughout the time they continued to grow.
“Historically, the generation of human-animal chimeras has suffered from low efficiency and integration of human cells into the host species,” Izpisua Belmonte says. “Generation of a chimera between human and non-human primate, a species more closely related to humans along the evolutionary timeline than all previously used species, will allow us to gain better insight into whether there are evolutionarily imposed barriers to chimera generation and if there are any means by which we can overcome them.”
The investigators performed transcriptome analysis on both the human and monkey cells from the embryos. “From these analyses, several communication pathways that were either novel or strengthened in the chimeric cells were identified,” Izpisua Belmonte explains. “Understanding which pathways are involved in chimeric cell communication will allow us to possibly enhance this communication and increase the efficiency of chimerism in a host species that’s more evolutionarily distant to humans.”
An important next step for this research is to evaluate in more detail all the molecular pathways that are involved in this interspecies communication, with the immediate goal of finding which pathways are vital to the developmental process. Longer term, the researchers hope to use the chimeras not only to study early human development and to model disease, but to develop new approaches for drug screening, as well as potentially generating transplantable cells, tissues, or organs.
An accompanying Preview in Cell outlines potential ethical considerations surrounding the generation of human/non-human primate chimeras. Izpisua Belmonte also notes that “it is our responsibility as scientists to conduct our research thoughtfully, following all the ethical, legal, and social guidelines in place.” He adds that before beginning this work, “ethical consultations and reviews were performed both at the institutional level and via outreach to non-affiliated bioethicists. This thorough and detailed process helped guide our experiments.”
This work was supported by the National Key Research and Development Program, the National Natural Science Foundation of China, Major Basic Research Project of Science and Technology of Yunnan, Key Projects of Basic Research Program in Yunnan Province, High-level Talent Cultivation Support Plan of Yunnan Province and Yunnan Fundamental Research Projects, UCAM, and the Moxie Foundation.
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Materials provided by Cell Press. Note: Content may be edited for style and length.

The complex patterns of genetic ancestry uncovered from genomic data in health care systems can provide valuable insights into both genetic and environmental factors underlying many common and rare diseases — insights that are far more targeted and specific than those derived from traditional ethnic or racial labels like Hispanic or Black, according to a team of Mount Sinai researchers.
In a study in the journal Cell, the team reported that this information could be used to better understand and predict which populations are more susceptible to certain disorders — including cancers, asthma, diabetes, and cardiovascular disease — and to potentially develop early interventions.
“This is the first time researchers have shown how genetic ancestry data could be used to enhance our understanding of disease risk and management at a health system level,” says senior author Eimear Kenny, PhD, Professor of Medicine, and Genetics and Genomic Sciences, at the Icahn School of Medicine at Mount Sinai. “By linking this data directly to health outcomes, we believe we’re contributing to an ongoing conversation to move beyond the current role of race and ethnicity in medicine.”
The research team drew from Mount Sinai’s BioMe™ BioBank program, recognized as one of the world’s leading repositories of genomic information for diverse populations, for its study. Using machine learning methodology, scientists identified 17 distinct ethnic communities from among the 30,000 participants in the BioMe BioBank. They then linked this data to thousands of health outcomes residing in Mount Sinai’s electronic health records. Among the findings was that 25 percent of BioMe participants had genetic links to populations — such as Ashkenazi Jewish and Puerto Rican — that predisposed them to certain genetic diseases.
“The traditional use of demographic data by health systems fails to capture the rich ethnic heritage of patients, and thus all the genetic and environmental factors that can affect rates of disease even within the same population,” says Dr. Kenny, who is Founding Director of the Institute for Genomic Health at Mount Sinai. “Our study used genomic data embedded in health system records to show how patients with origins from different countries in the Americas can have different rates of disease. For example, people of Puerto Rican and Mexican descent are broadly classified as Hispanic or Latinx, yet the former population has one of the highest rates of asthma in the world, while the latter population has one of the lowest.”
The Mount Sinai study cited the APOL1 gene, which can confer a significantly greater risk of kidney and cardiovascular disease, as another reason for moving beyond the traditional demographic labels used by health care systems. The risk variants of APOL1 are most frequently seen in populations across the Americas that share African genetic ancestry. However, there are many populations around the world of African descent that might not self-identify as African, and thus be unaware that they might harbor those risk variants. Furthermore, that knowledge gap may result in these populations being underrepresented in APOL1 research.
“Our study underscores that there are limits to the narrow demographic labels used in medicine and research today — and society in general, for that matter — to attempt to characterize disease and its risk factors,” says Dr. Kenny. “The types of information that can be derived from using biological markers of ancestry, however, convey a much richer and more sophisticated layer of understanding of disease risk and burden, one that could have enormous implications for health care systems globally.”

More than 20 years after the launch of a landmark clinical trial, follow-up examinations and analyses found that not all patients with elevated eye pressure need pressure-lowering treatment to prevent vision loss from glaucoma.
When the study was launched, it was universally accepted that all patients with elevated eye pressure should be given medication to lower that pressure. The Ocular Hypertension Treatment Study — funded by the National Eye Institute of the National Institutes of Health (NIH) and led by researchers at Washington University School of Medicine in St. Louis — recruited more than 1,600 patients nationally who were at moderate to high risk for glaucoma because of elevated eye pressure. The purpose was to evaluate how successful medication was at preserving vision.
Half of the patients were randomly selected to receive daily treatment with eye drops to lower intraocular pressure, and the other half were observed without treatment. After seven years, when the treatment had been shown to be highly effective, patients in both groups were given the treatment. In this latest phase of the study, researchers evaluated which patients went on to develop glaucoma after the initial study had concluded.
As reported online April 15 in the journal JAMA Ophthalmology, the researchers found that about 25% of study participants went on to develop vision loss from glaucoma in at least one eye, a lower rate than what was expected. The conventional thinking had been that most patients with elevated eye pressure probably should receive treatment.
“But treating elevated eye pressure can be expensive and inconvenient, so we wanted to determine whether all individuals with high pressure should be treated,” said Michael A. Kass, MD, the Bernard Becker Professor of Ophthalmology & Visual Sciences. “With only 25% of the individuals in the study developing vision loss in one or both eyes after all these years, we know now that not all of those patients needed to be treated.”
Glaucoma is one of the leading causes of blindness in the United States and the No. 1 cause of blindness in Black Americans. Elevated eye pressure develops in 4% to 7% of the people in the United States over age 40, and the conventional wisdom prior to the study had been to prescribe pressure-lowering drops. But those medications can cost hundreds of dollars per year; they can cause side effects in some people; and many people, especially older individuals, find it difficult to put drops in their eyes every day.

Researchers from Kumamoto University (Japan) have found that the anti-diabetic drug metformin significantly prolongs the survival of mice in a model that simulates the pathology of non-diabetic chronic kidney disease (ND-CKD) by ameliorating pathological conditions like reduced kidney function, glomerular damage, inflammation and fibrosis. Metformin’s mechanism is different from existing therapeutics which only treat symptoms, such as the blood pressure drug losartan, so the researchers believe that a combination of these medications at low dose will be highly beneficial.
CKD (chronic kidney disease) is a general term for kidney damage that results from persistent decline in kidney function due to proteinuria, kidney inflammation, or fibrosis. As CKD progresses, patients are forced to undergo dialysis, and diabetes is one of its biggest risk factors. CKD can also occur in association with lifestyle-related conditions such as hypertension, insufficient exercise, smoking, hyperuricemia, and mutations in kidney-related genes. This type of CKD is classified as non-diabetic chronic kidney disease (ND-CKD) and has limited treatment options.
Alport syndrome is an inherited kidney disease that falls under the ND-CKD umbrella. In Alport syndrome, abnormalities in type 4 collagen, a constituent of the membrane responsible for urine filtration in the kidney, cause abnormal glomerular filtration which results in chronic loss of kidney function. It is a serious disease that eventually progresses to end-stage renal failure, requiring dialysis or kidney transplant. As with diabetic kidney disease and ND-CKD, Alport syndrome is currently treated by maintaining kidney function using blood pressure-lowering drugs but patients eventually transition to end-stage renal failure. Therefore, a new therapeutic agent that is effective and safe enough to be administered to patients for a long period of time is needed.
Metformin is used as a treatment for type 2 diabetes because it improves insulin sensitivity. It is an inexpensive and safe drug that has been used by diabetics for many years. Interestingly, because of its mechanism of action, metformin was also known to be protective against many diseases involving inflammation and fibrosis, and was known to improve the renal pathology of diabetic kidney disease. However, it was unclear whether metformin also had a protective effect on ND-CKD, which is not caused by diabetes.
Researchers selected an Alport syndrome mouse model for their ND-CKD experiments and worked to identify novel therapeutic targets based on pathogenic mechanisms. They focused on drugs traditionally used for CKD patients, metformin and losartan — which works by lowering blood pressure and inhibiting proteinuria caused by increased glomerular filtration.
Administration of metformin or losartan to ND-CKD model mice significantly suppressed proteinuria and serum creatinine, which are indicators of CKD. Inflammation and fibrosis, which also reduce kidney function, significantly improved. Furthermore, metformin was found to have a nephroprotective effect similar to losartan.
The results of a detailed gene expression analysis found that the renal pathology of the ND-CKD mouse model was caused by abnormal expression of genes related to glomerular epithelial cell podocytes (cells responsible for kidney filtering) and genes involved in intracellular metabolism. Interestingly, the improvement caused by losartan was limited to genes involved in podocyte abnormalities. Metformin, on the other hand, improved the expression of genes related to podocyte abnormalities and those related to intracellular metabolism. In other words, metformin clearly has a different target of action (also improved targeting of metabolic abnormalities) from that of losartan.
Finally, they found that administration of low-dose metformin and losartan to model mice significantly prolonged their survival. Researchers also found that in studies using doses at which metformin alone was not effective, the combination of metformin and losartan significantly prolonged mice survival. Put plainly, this study showed that an appropriate combination of the two therapeutic drugs could effectively treat the ND-CKD (Alport syndrome) mouse model.
This study raises the possibility that metformin, a proven and inexpensive diabetic drug, may delay the progression of kidney pathology in ND-CKD, including Alport syndrome. Metformin is currently available for use in patients with diabetes in clinical practice, but not in non-diabetic patients.
“This study appears to show that metformin has therapeutic effects for both diabetic and non-diabetic kidney disease,” said Professor Hirofumi Kai, who led the research project. “However, metformin is contraindicated in patients with severe renal dysfunction (eGFR < 30) due to the development of lactic acidosis as a side effect and should be administered with caution to patients with mild to moderate renal dysfunction." This research found that the appropriate combination of metformin and losartan significantly improved renal pathology and prolonged survival in a ND-CKD mouse model. This suggests that the old inexpensive drug metformin could become a new inexpensive drug for patients with chronic kidney disease.

The causes of the serious muscle disease ALS still remain unknown. Now, researchers at Karolinska Institutet and KTH Royal Institute of Technology, among others, have examined a type of cell in the brain blood vessels that could explain the unpredictable disease origins and dynamics. The results indicate a hitherto unknown connection between the nervous and vascular systems. The study, which is published in Nature Medicine, has potential implications for earlier diagnoses and future treatments.
ALS (amyotrophic lateral sclerosis) is a neurodegenerative disease of the motor neurons that eventually causes muscular atrophy, paralysis and death. There is currently no cure.
The cause of ALS is only understood in the 5 to 10 per cent of patients who have an inherited form of the disease. To help in its early detection and to develop efficacious therapies, researchers are avidly seeking a clearer picture of the disease’s pathogenesis.
ALS patients demonstrate high variability of age at onset, non-motor symptoms and survival. In recent years, research has shifted focus from neurological explanations to these differences, and has taken an interest, for example, in the cerebral vascular system, which delivers oxygen and nutrients to brain tissue.
Researchers at Karolinska Institutet, KTH Royal Institute of Technology, SciLifeLab, London’s Imperial College and Umeå University have now studied whether a possible connection exists between perivascular fibroblast cells and the time of disease onset and survival.
Studies on mice with ALS showed that genes for perivascular fibroblasts were active already in an early asymptomatic stage of the disease and months before neuronal damage began to appear.
The researchers then examined the levels of a large number of potential marker proteins in the plasma of 574 patients with a recent ALS diagnosis and 504 healthy controls from four countries.
Their results suggest a correlation between elevated levels of the protein marker SPP1 for perivascular fibroblasts and an aggressive disease process and shorter survival. This is the first time a connection between the vascular and nervous systems in sporadic ALS has been observed.
“It is exciting to see how the results from our protein profiling could be connected to the long range of cellular and molecular analysis that we have done and reveal the identified association to disease progression,” says the first author Anna Månberg, researcher at the Department of Protein Science, at KTH and SciLifeLab.
“Our results indicate that vascular events are a factor in the disease’s heterogeneity and can improve our knowledge of early stage ALS,” says the study’s last and senior author Sebastian Lewandowski, researcher at the Department of Clinical Neuroscience and the Centre for Molecular Medicine at Karolinska Institutet. “More studies are now needed on vascular disease mechanisms for better prognostic tools and future treatments.”
The research was financed by the Olle Engkvist Foundation, the Ulla-Carin Lindquist Foundation for ALS Research, the Swedish FTD Initiative and others, and received strategic support from the Knut and Alice Wallenberg Foundation and the Erling-Persson Family Foundation for the KTH Center for Applied Precision Medicine (KCAP). 
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Materials provided by Karolinska Institutet. Note: Content may be edited for style and length.