Blood test finds knee osteoarthritis up to eight years before it appears on x-rays

A blood test successfully predicted knee osteoarthritis at least eight years before tell-tale signs of the disease appeared on x-rays, Duke Health researchers report.
In a study appearing April 26 in the journal Science Advances, the researchers validated the accuracy of the blood test that identifies key biomarkers of osteoarthritis. They showed that it predicted development of the disease, as well as its progression, which was demonstrated in their earlier work.
The research advances the utility of a blood test that would be superior to current diagnostic tools that often don’t identify the disease until it has caused structural damage to the joint.
“Currently, you’ve got to have an abnormal x-ray to show clear evidence of knee osteoarthritis, and by the time it shows up on x-ray, your disease has been progressing for some time,” said senior author Virginia Byers Kraus, M.D., Ph.D., a professor in the departments of Medicine, Pathology, and Orthopedic Surgeryat Duke University School of Medicine. “What our blood test demonstrates is that it’s possible to detect this disease much earlier than our current diagnostics permit.”
Osteoarthritis (OA) is the most common form of arthritis, afflicting an estimated 35 million adults in the U.S. and causing significant economic and societal impacts. While there are currently no cures, the success of potential new therapies could hinge on identifying the disease early and slowing its progression before it becomes debilitating.
Kraus and colleagues have focused on developing molecular biomarkers that can be used for both clinical diagnostic purposes and as a research tool to aid in the development of effective drugs. In previous studies, the blood biomarker test demonstrated 74% accuracy in predicting knee OA progression and 85% accuracy in diagnosing knee OA.
The current study further honed the test’s predictive capabilities. Using a large United Kingdom database, the researchers analyzed serum of 200 white women, half diagnosed with OA and the other half without the disease, matched by body mass index and age.

They found that a small number of biomarkers in the blood test successfully distinguished the women with knee OA from those without it, catching molecular signals of OA eight years before many of the women were diagnosed with the disease by x-ray.
“This is important because it provides more evidence that there are abnormalities in the joint that can be detected by blood biomarkers well before x-rays can detect OA,” Kraus said. “Early-stage osteoarthritis could provide a ‘window of opportunity’ in which to arrest the disease process and restore joint health.”
In addition to Kraus, study authors include Shuming Sun, Alexander Reed, Erik J. Soderblom, M Arthur Moseley, Kaile Zhou, Vaibhav Jain, Nigel Arden, and Yi-Ju Li.
The study received funding support from National Institutes of Health (R01-AR071450 and P30-AG028716).

Read more →

How geography acts as a structural determinant of health

In unincorporated communities in the United States-Mexico borderlands, historically and socially marginalized populations become invisible to the healthcare system, showing that geography acts as a structural determinant of health for low-income populations. So concludes a study by a University of California, Riverside, team that focused its attention on the borderland in Southern California, specifically, eastern Coachella Valley.
From September to December 2020, the team, led by Ann Cheney, an associate professor of social medicine, population, and public health in the School of Medicine, conducted interviews in collaboration with María Pozar, a community investigator and CEO of Conchita Servicios de la Comunidad, with 36 Latinx and Indigenous Mexican caregivers of children with asthma or respiratory distress. The researchers found communities in the “colonias” (unincorporated areas in the borderlands) lack basic critical infrastructure including healthcare access.
The U.S.-Mexico borderland is home to nearly 2.7 million Hispanic or Latinx individuals. The immigrant population in the colonias has limited English proficiency, health literacy levels, and income, and lower levels of formal education. Many are undocumented.
“Our work shows the importance of geography in health and how geography acts as a structural determinant of health,” Cheney said. “For example, foreign-born caregivers who speak Spanish or Purépecha prefer to take their children across the U.S.-Mexico border for respiratory health care because physicians there provide them with a diagnosis and treatment plan that they perceive improves their children’s health.”
The study, published in the journal Social Science & Medicine, found the caregivers perceive U.S.-based physicians as not providing them with sufficient information since most physicians do not speak their language and do not adequately listen to or are dismissive of their concerns about their children’s respiratory health. The caregivers perceive Mexican-based physicians as providing them with a diagnosis and treatment plan, whereas U.S.-based physicians often prescribe medications and provide no concrete diagnosis.
“Further, only those with legal documentation status can cross the border, which contributes to disparities in children’s respiratory health,” Cheney said. “Thus, caregivers without legal status in the U.S. must access healthcare services in the U.S. for their children and receive, what these caregivers perceive, as suboptimal care.”
Cheney added she was surprised to learn that caregivers who did not have legal documentation status in the U.S. asked trusted family and friends to take their children across the border to receive healthcare services for childhood asthma and related conditions.

“Geography, meaning living in unincorporated communities, harms health,” she said. “Geography and the politics of place determines who can and cannot cross borders.”
Study participants discussed the distance they needed to travel to pediatric specialty care for the care and management of their children’s respiratory health problems. Some commented on the lack of interaction and communication with physicians during medical visits. Some participants commented on the lack of physicians’ knowledge about the connections between their children’s exposure to environmental hazards and poor respiratory health and allergic symptoms.
The research took place in four unincorporated rural communities — Mecca, Oasis, Thermal, and North Shore — in eastern Coachella Valley, along the northern section of the Salton Sea. People living in the colonias here are subject to the health effects of environmental hazards. Many are farmworkers living and working in the nearby agricultural fields. Most of the workforce lives in mobile parks and below the federal poverty line.
“In addition to toxic water and dust from the Salton Sea, other environmental health hazards, such as agriculture pesticide exposure, waste processing facilities, and unauthorized waste dumps, also contribute to this community’s high incidence of poor respiratory health,” said Gabriela Ortiz, the first author of the research paper and a graduate student in anthropology who works with Cheney. “These communities are vulnerable to the policies and governing decisions around exposure to environmental hazards and infrastructure development. The absence of infrastructure and lack of healthcare infrastructure limits their access to primary care and specialty care services.”
Ortiz explained that anthropologists and social scientists have long argued that environmental injustices are a product of structural violence.
“This is indirect violence caused by social structures and institutions that prevent individuals from meeting their basic needs because of political economic domination and class-based exploitation,” she said. “Understanding the complex interplay between geography, borderlands, and health is essential for coming up with effective public health policy and interventions.”
The title of the research paper is “Seeking care across the US-Mexico border: The experiences of Latinx and Indigenous Mexican caregivers of children with asthma or respiratory distress.”
Cheney, Ortiz, and Pozar were joined in the study by Ashley Moran and Sophia Rodriquez of UCR.
The study was funded by the National Institutes of Health/National Institute of Minority Health and Health Disparities.

Read more →

Getting dynamic information from static snapshots

Imagine predicting the exact finishing order of the Kentucky Derby from a still photograph taken 10 seconds into the race.
That challenge pales in comparison to what researchers face when using single-cell RNA-sequencing (scRNA-seq) to study how embryos develop, cells differentiate, cancers form, and the immune system reacts.
In a paper published today in Proceedings of the National Academy of Sciences, researchers from the UChicago Pritzker School of Molecular Engineering and the Chemistry Department have created TopicVelo, a powerful new method of using the static snapshots from scRNA-seq to study how cells and genes change over time.
The team took an interdisciplinary, collaborative approach, incorporating concepts from classical machine learning, computational biology, and chemistry.
“In terms of unsupervised machine learning, we use a very simple, well-established idea. And in terms of the transcriptional model we use, it’s also a very simple, old idea. But when you put them together, they do something more powerful than you might expect,” said PME Assistant Professor of Molecular Engineering and Medicine Samantha Riesenfeld, who wrote the paper with Chemistry Department Prof. Suriyanarayanan Vaikuntanathan and their joint student, UChicago Chemistry PhD candidate Cheng Frank Gao.
The trouble with pseudotime
Researchers use scRNA-seq to get measurements that are powerful and detailed, but by nature are static.

“We developed TopicVelo to infer cell-state transitions from scRNA-seq data,” Riesenfeld said. “It’s hard to do that from this kind of data because scRNA-seq is destructive. When you measure the cell this way, you destroy the cell.”
This leaves researchers a snapshot of the moment the cell was measured/destroyed. While scRNA-seq gives the best available transcriptome-wide snapshot, the information many researchers need, however, is how the cells transition over time. They need to know how a cell becomes cancerous or how a particular gene program behaves during an immune response.
To help figure out dynamic processes from a static snapshot, researchers traditionally use what’s called “pseudotime.” It’s impossible to watch an individual cell or gene’s expression change and grow in a still image, but that image also captured other cells and genes of the same type that might be a little further on in the same process. If the scientists connect the dots correctly, they can gain powerful insights into how the process looks over time.
Connecting those dots is difficult guesswork, based on the assumption that similar-looking cells are just at different points along the same path. Biology is much more complicated, with false starts, stops, bursts, and multiple chemical forces tugging on each gene.
Instead of traditional pseudotime approaches, which look at the expression similarity among the transcriptional profiles of cells, RNA velocity approaches look at the dynamics of transcription, splicing and degradation of the mRNA within those cells.
It’s a promising but early technology.

“The persistent gap between the promise and reality of RNA velocity has largely restricted its application,” the authors wrote in the paper.
To bridge this gap, TopicVelo puts aside deterministic models, embracing — and gleaning insights from — a far more difficult stochastic model that reflects biology’s inescapable randomness.
“Cells, when you think about them, are intrinsically random,” said Gao, the first author on the paper. “You can have twins or genetically identical cells that will grow up to be very different. TopicVelo introduces the use of a stochastic model. We’re able to better capture the underlying biophysics in the transcription processes that are important for mRNA transcription.”
Machine learning shows the way
The team also realized that another assumption limits standard RNA velocity. “Most methods assume that all cells are basically expressing the same big gene program, but you can imagine that cells have to do different kinds of processes simultaneously, to varying degrees,” Riesenfeld said. Disentangling these processes is a challenge.
Probabilistic topic modeling — a machine learning tool traditionally used to identify themes from written documents — provided the UChicago team with a strategy. TopicVelo groups scRNA-seq data not by the types of cell or gene, but by the processes those cells and genes are involved in. The processes are inferred from the data, rather than imposed by external knowledge.
“If you look at a science magazine, it will be organized along topics like ‘physics,’ ‘chemistry’ and ‘astrophysics,’ these kinds of things,” Gao said. “We applied this organizing principle to single-cell RNA-sequencing data. So now, we can organize our data by topics, like ‘ribosomal synthesis,’ ‘differentiation,’ ‘immune response,’ and ‘cell cycle’. And we can fit stochastic transcriptional models specific to each process.”
After TopicVelo disentangles this kludge of processes and organizes them by topic, it applies topic weights back onto the cells, to account for what percentage of each cell’s transcriptional profile is involved in which activity.
According to Riesenfeld, “This approach helps us look at the dynamics of different processes and understand their importance in different cells. And that’s especially useful when there are branch points, or when a cell is pulled in different directions.”
The results of combining the stochastic model with the topic model are striking. For example, TopicVelo was able to reconstruct trajectories that previously required special experimental techniques to recover. These improvements greatly broaden potential applications.
Gao compared the paper’s findings to the paper itself — the product of many areas of study and expertise.
“At PME, if you have a chemistry project, chances are there’s a physics or engineering student working on it,” he said. “It’s never just chemistry.”

Read more →

Component of keto diet plus immunotherapy may reduce prostate cancer

Adding a pre-ketone supplement — a component of a high-fat, low-carb ketogenic diet — to a type of cancer therapy in a laboratory setting was highly effective for treating prostate cancer, researchers from the University of Notre Dame found.
Recently published online in the journal Cancer Research, the study from Xin Lu, the John M. and Mary Jo Boler Collegiate Associate Professor in the Department of Biological Sciences, and collaborators tackled a problem oncologists have battled: Prostate cancer is resistant to a type of immunotherapy called immune checkpoint blockade (ICB) therapy. ICB therapy blocks certain proteins from binding with other proteins and paves the way for our body’s fighter cells, T cells, to kill the cancer.
“Prostate cancer is the most common cancer for American men, and immunotherapy has been really influential in some other cancers, like melanoma or lung cancer, but it hasn’t been working almost at all for prostate cancer,” said Lu, who is affiliated with the Boler-Parseghian Center for Rare and Neglected Diseases. Adding a dietary supplement might overcome this resistance, the lead author in the study, Sean Murphy, suggested.
Murphy, a ’24 alumnus who was a doctoral student in Lu’s lab, had been following a keto diet himself. Knowing that cancer cells feed off of sugar, he decided that depriving mouse models of carbohydrates — a key component of the keto diet — might prevent cancer growth.
He divided the models into different groups: immunotherapy alone, ketogenic diet alone, a pre-ketone supplement alone, the ketogenic diet with the immunotherapy, the supplement with the immunotherapy, and the control. While the immunotherapy alone had almost no effect on the tumors (just like what happens to most patients with prostate cancer), both the ketogenic diet with the immunotherapy and the pre-ketone supplement with the immunotherapy reduced the cancer and extended the lives of the mouse models.
The supplement with the immunotherapy worked best.
“It turned out this combination worked really well,” Lu said. “It made the tumor become very sensitive to the immunotherapy, with 23 percent of the mice cured — they were tumor-free; in the rest, the tumors were shrinking really dramatically.”
The evidence points to the possibility that a supplement providing ketones, which are what is produced in the body when people eat a keto diet, might prevent the prostate cancer cells from being resistant to immunotherapy. This may lead to future clinical studies that examine how ketogenic diets or keto supplements could enhance cancer therapy.

While keto diets allow for minimal carbohydrates, the success of this study is not about the lack of carbohydrates, Murphy and Lu stressed. It is about the presence of the ketone body, a substance produced by the liver and used as an energy source when glucose is not available. The ketones disrupt the cycle of the cancer cells, allowing the T cells to do their job to destroy them.
The discovery was also exciting on a molecular level, Lu said. Any type of dietary study can suffer from the potential issue of causation: Are the results from the diet or other changes made because of the diet? But Lu and his collaborators confirmed their results using single-cell RNA sequencing, which examines the gene expression of single cells within the tumor.
“We found that this combination of the supplement and the immunotherapy reprogrammed the whole immune profile of the tumors and recruited many T cells into the tumors to kill prostate cancer cells,” Lu said.
The successful therapy also reduced the number of a type of immune cell called neutrophils. Once in the tumor microenvironment, neutrophils’ natural properties become greatly distorted, and they become largely responsible for inhibiting T cell activities and allowing more tumor progression. Dysregulation of neutrophils is also associated with many other diseases.
“With the main ketone body depleting neutrophils, it opens the door for investigating the effects of the keto diet and the ketone supplement on diseases ranging from inflammatory bowel disease to arthritis,” Murphy said.
Lu agreed.
“What’s exciting is that we’re getting closer to the mechanism, backed up by genetic models and what we’re seeing in the tumors themselves, of why this works,” he said.

Read more →

Pregnancy cytokine levels impact fetal brain development and offspring behavior

Researchers at Weill Cornell Medicine have discovered in a preclinical model that cytokines, proteins that control immune response, circulating in maternal blood during pregnancy may mitigate an offspring’s risk for psychiatric conditions. The findings are surprising because circulating maternal cytokines are at such low levels that they were not implicated in fetal brain development and offspring behavior before.
The study published online in Brain, Behavior, and Immunity on Feb. 29, reported that cytokine XCL1 produced by maternal immune cells can function as a pregnancy hormone and is required for the proper development of placenta and male offspring fear behavior. These results support epidemiological studies which have long suggested a link between human maternal infection and inflammation during pregnancy and offspring developing psychiatric disorders later life.
“Using mouse models, we found that circulating XCL1 normally remained at the same low pre-pregnancy level throughout gestation except for a short rise and fall in the middle period,” said corresponding author Dr. Miklos Toth, professor of pharmacology at Weill Cornell Medicine. “This temporary rise is essential for the proper development of the placenta and offspring emotional behavior.” First author Dr. Rosa Chen was a graduate student in the Toth lab during the study, which was a collaboration with Dr. Heidi Stuhlmann, acting chair of Biochemistry and also of Cell and Developmental Biology and the Harvey Klein Professor of Biomedical Sciences, Cell and Developmental Biology at Weill Cornell Medicine.
When this spike in XCL1 in maternal blood was blocked genetically or neutralized by anti-XCL1 antibodies, the researchers found increased production of factors associated with tissue damage in the fetal placenta which led to increased innate anxiety and stress reactions in male mouse offspring. The researchers also found a neuronal abnormality in the developing brains of these offspring, specifically in the ventral hippocampus, a region that has been linked to anxiety and anxious behavior.
The immune and neuronal abnormalities observed when the cytokine spike was blocked were normalized by adulthood, suggesting that the adult anxious behavior of the offspring could be related to the early life proinflammatory state caused by the absence of elevated XCL1.
Dr. Toth will explore other chemokines that may regulate placenta development and impact offspring emotional behavior. The team plans to collaborate with researchers who have access to blood samples from pregnant women to see if the profile of XCL1, a protein also found in humans, corresponds to the observations in mouse models.

Read more →

People with rare longevity mutation may also be protected from cardiovascular disease

A new study highlights possible cardiovascular health advantages in individuals with a rare condition known as growth hormone receptor deficiency (GHRD), also called Laron syndrome.
GHRD, which is characterized by the body’s impaired ability to use its own growth hormone and results in stunted growth, has been linked in mice to a record 40% longevity extension and lower risks for various age-related diseases. However, the risk of cardiovascular disease in individuals with GHRD has remained unclear until now, leading to the speculation that in people, this mouse longevity mutation may actually increase cardiovascular disease.
The study, appearing in Med on April 26, 2024, is the latest product of an international collaboration spanning nearly 20 years between Valter Longo, professor of gerontology at the USC Leonard Davis School of Gerontology, and endocrinologist Jaime Guevara-Aguirre of the Universidad San Francisco de Quito, Ecuador.
Over the past two decades, Longo, Guevara-Aguirre and colleagues have examined the health and aging of people with the gene mutation that causes GHRD. This rare mutation — found in just 400 to 500 people worldwide — was identified in a group of Ecuadorians whose ancestors had fled Spain during the Inquisition more than three centuries ago. The mutation leaves them with ineffective growth hormone receptors and results in a type of dwarfism.
The team’s previous research has indicated that while GHRD/Laron syndrome reduces growth, it also appears to reduce the risk of several age-related diseases. Although the Ecuadorians with GHRD have a higher rate of obesity, they have a very low risk of cancer and Type 2 diabetes. They also appear to have healthier brains and better performance on tests of cognition and memory.
For the current study, the research team examined cardiovascular function, damage, and risk factors in GHRD subjects and their relatives. Researchers conducted two phases of measurements in Los Angeles and Ecuador, involving a total of 51 individuals, with 24 diagnosed with GHRD and 27 relatives without GHRD serving as controls.
Key findings from the study included: GHRD subjects displayed lower blood sugar, insulin resistance, and blood pressure compared to the control group. They also had smaller heart dimensions and similar pulse wave velocity — a measure of stiffness in the arteries — but had lower carotid artery thickness compared to control subjects. Despite elevated low-density lipoprotein (LDL), or “bad cholesterol,” levels, GHRD subjects showed a trend for lower carotid artery atherosclerotic plaques compared to controls (7% vs 36%).”These findings suggest that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors compared to their relatives,” said Longo, senior author of the new study. “Although the population tested is small, together with studies in mice and other organisms this human data provide valuable insights into the health effects of growth hormone receptor deficiency and suggest that drugs or dietary interventions that cause similar effects could reduce disease incidence and possibly extend longevity.”
Along with co-corresponding authors Longo and Guevara-Aguirre, the study’s coauthors included Amrendra Mishra and Priya Balasubramanian of USC; Carolina Guevara, Álvaro Villacres, Gabriela Peña, and Daniela Lescano of the Universidad San Francisco de Quito; Alexandra Guevara of the Instituto de Endocrinologia Metabolismo y Reproducción (IEMYR) in Quito; Marco Canepa of the University of Genova, Italy; and John Kopchick of Ohio University. Funding including National Institutes of Health/National Institute on Aging grant P01 AG034906 to Longo.

Read more →

Biden Delays Ban on Menthol Cigarettes

The proposal had been years in the making, in an effort to curb death rates of Black smokers targeted by Big Tobacco. In an election year, the president’s weak support among Black voters may have influenced the postponement.The Biden administration said on Friday that it was delaying a decision on whether to ban menthol cigarettes as federal officials take more time to consider the move.The White House has faced considerable opposition from the big tobacco companies that could lose billions of dollars from the move. But the proposal has also posed risks for President Biden in an election year because of his weakening support among Black voters, some of whom view it as heavy-handed.“This rule has garnered historic attention, and the public comment period has yielded an immense amount of feedback, including from various elements of the civil rights and criminal justice movement,” Xavier Becerra, the health and human services secretary, said in a statement.“It’s clear that there are still more conversations to have, and that will take significantly more time.”The delay runs counter to a major push by federal regulators, who saw a ban was a way to save lives and lower lung cancer deaths. The idea had united an array of public health groups, including leading lung, heart, cancer and pediatricians associations.They cite years of data suggesting that menthol cigarettes, long marketed to African-American smokers, make it more palatable to start smoking and more difficult to stop.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Read more →

How is the King’s cancer treatment going?

Published24 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, PA MediaBy Smitha MundasadHealth reporter It has been almost three months since King Charles was diagnosed with an unspecified type of cancer. At the time the monarch, 75, said he remained “wholly positive” about his treatment and looked forward to returning to public duties as soon as possible. And although he postponed his public-facing duties, he continued with his constitutional work as head of state, including doing paperwork and private meetings. He is now “greatly encouraged” to be resuming some public duties while continuing treatment for cancer. How is the King doing now? Buckingham Palace’s tone is positive.It says the King’s medical team is “very encouraged” about his continued recovery and that his doctors have been “sufficiently pleased” with progress made so far. Some of his engagements will be adapted, if needed, “to minimise any risks to His Majesty’s continued recovery”. For example, he will not take on a full summer programme.The King, has generally led a fit and active life, with few reported medical problems.His cancer was discovered incidentally during a procedure for a benign (non-cancerous) prostate enlargement. As soon as the cancer was spotted he quickly started a course of treatment. Experts know that catching and treating cancer early gives the best chance of a good recovery. Is he still having treatment?The Palace says his “treatment programme” will continue and it is too early to say how long that might last. It has not given any details about the type of treatment the King is having.Cancer treatments can come in many different forms.Some are more intensive – requiring lots of hospital trips – and have more side effects than others. Other ones can be given at home.What will the King’s public duties be after return?There are many different ways of tackling cancer, including surgery, chemotherapy and radiotherapy to remove or destroy cancerous cells. Often a combination of different approaches is used. Follow-up care can be very important too – including scans and regular checks. Some people may receive cancer treatment for weeks, months or years. This might be to prevent cancer from returning, put cancer into remission or help control the progression of cancer, for example.Some rounds of treatment can dampen the immune system for a while – meaning the risk of infections can be increased. Is there a risk the King may be taking on too much? Buckingham Palace says the King’s diary will be “carefully calibrated” as his recovery continues. His medical team will be in close consultation and make sure he gets all the treatment he needs. They won’t want any of his duties to hinder that progress and his engagements can be adapted, if necessary. Cancer, and the treatments given to stop it, can cause extreme tiredness or fatigue. And that can vary throughout the day, with each day being different. What type of cancer does the King have?The palace has not disclosed details about the type of cancer the King has but has said it is not prostate cancer. Like any patient, medical details are private. Buckingham Palace says: “His Majesty is greatly encouraged to be resuming some public-facing duties and very grateful to his medical team for their continued care and expertise.”What is it like to live with cancer? The King joins the legions of people around the world living with cancer. One in two people in the UK develop some kind of cancer during their lifetime.It’s a diagnosis that impacts not just your health but your social, family and working life too. After taking some time off, His Majesty will shortly return to public-facing duties. Notably, his first visit next week will be to a cancer treatment centre. He now understands first-hand what living with cancer can entail, although the journey is different for each individual affected. His may not be the typical story, but he says he is deeply grateful for the kindness and good wishes he has received since going public about it.There is practical support and information out there for people trying to navigate their way, juggling cancer treatment alongside all the daily responsibilities of life, like paying the bills.Emotional support is vital too. You may want to talk to someone you know well – a partner or friend – or perhaps someone you do not know so well, like your doctor or a specialist nurse. Some organisations such as Mind and MacMillan can offer this type of support too. More on this storyWhat do we know about the King’s cancer diagnosis?Published22 minutes agoKing Charles diagnosed with cancerPublished6 February

Read more →

Automated machine learning robot unlocks new potential for genetics research

University of Minnesota Twin Cities researchers have constructed a robot that uses machine learning to fully automate a complicated microinjection process used in genetic research.
In their experiments, the researchers were able to use this automated robot to manipulate the genetics of multicellular organisms, including fruit fly and zebrafish embryos. The technology will save labs time and money while enabling them to more easily conduct new, large-scale genetic experiments that were not possible previously using manual techniques
The research is featured on the cover of the April 2024 issue of GENETICS, a peer-reviewed, open access, scientific journal. The work was co-led by two University of Minnesota mechanical engineering graduate students Andrew Alegria and Amey Joshi. The team is also working to commercialize this technology to make it widely available through the University of Minnesota start-up company, Objective Biotechnology.
Microinjection is a method for introducing cells, genetic material, or other agents directly into embryos, cells, or tissues using a very fine pipette. The researchers have trained the robot to detect embryos that are one-hundredth the size of a grain of rice. After detection, the machine can calculate a path and automate the process of the injections.
“This new process is more robust and reproducible than manual injections,” said Suhasa Kodandaramaiah, a University of Minnesota mechanical engineering associate professor and senior author of the study. “With this model, individual laboratories will be able to think of new experiments that you couldn’t do without this type of technology.”
Typically, this type of research requires highly skilled technicians to perform the microinjection, which many laboratories do not have. This new technology could expand the ability to perform large experiments in labs, while reducing time and costs.
“This is very exciting for the world of genetics. Writing and reading DNA have drastically improved in recent years, but having this technology will increase our ability to perform large-scale genetic experiments in a wide range of organisms,” said Daryl Gohl, a co-author of the study, the group leader of the University of Minnesota Genomics Center’s Innovation Lab and research assistant professor in the Department of Genetics, Cell Biology, and Development.

Not only can this technology be used in genetic experiments, but it can also help to preserve endangered species through cryopreservation, a preservation technique conducted at ultra-low temperatures.
“You can use this robot to inject nanoparticles into cells and tissues that helps in cryopreservation and in the process of rewarming afterwards,” Kodandaramaiah explained.
Other team members highlighted other applications for the technology that could have even more impact.
“We hope that this technology could eventually be used for in vitro fertilization, where you could detect those eggs on the microscale level,” said Andrew Alegria, co-lead author on the paper and University of Minnesota mechanical engineering graduate research assistant in the Biosensing and Biorobotics Lab.

Read more →

Air pollution and depression linked with heart disease deaths in middle-aged adults

A study in more than 3,000 US counties, with 315 million residents, has suggested that air pollution is linked with stress and depression, putting under-65-year-olds at increased risk of dying from cardiovascular disease. The research is presented today at ESC Preventive Cardiology 2024, a scientific congress of the European Society of Cardiology (ESC).1
“Our study indicates that the air we breathe affects our mental well-being, which in turn impacts heart health,” said study lead author Dr. Shady Abohashemof Harvard Medical School, Boston, US.
According to the World Health Organization, air pollution is estimated to have caused 4.2 million premature deaths worldwide in 2019.2 Mental illness has also been linked with premature death.3 This study examined whether air pollution and poor mental health are interrelated and have a joint impact on death from cardiovascular disease.
The study focused on particles less than 2.5 micrometres in diameter, also referred to as fine particles or PM2.5. They come from vehicle exhaust fumes, power plant combustion, and burning wood, and present the highest health risk. To conduct the study, county-level data on annual PM2.5 levels were obtained from the Centers for Disease Control and Prevention (CDC).4 PM2.5 exposure was categorised as high or low according to World Health Organization (WHO) standards. The researchers gathered data on the average number of days (age-standardised) that county residents experienced mental health issues — including stress, depression, and emotional problems — from the CDC.5 Each county was then categorised into three groups based on these numbers. Counties in the top third reported the most days of poor mental health (PMH).4 Age-adjusted premature cardiovascular mortality rates (under 65 years of age) per county, were obtained from the CDC.6 County characteristics were sourced from the County Health Rankings project.
The study included 3,047 US counties, representing 315,720,938 residents (with over 207 million aged 20 to 64 years and 50% females) in 2013. Between 2013 and 2019, some 1,079,656 (0.34%) participants died from cardiovascular disease before the age of 65 years. The researchers analysed the associations between pollution, mental health, and premature cardiovascular mortality after adjusting for factors that could influence the relationships.7
Counties with dirty air (high PM2.5 concentrations) were 10% more likely to report high levels of PMH days compared to counties with clean air (low PM2.5 concentrations). That risk was markedly greater in counties with a high prevalence of minority groups or poverty. The link between PMH and premature cardiovascular mortality was strongest in counties with higher levels (above WHO recommended levels: ≥10 µm2) of air pollution. In these counties, higher levels of PMH were associated with a three-fold increase in premature cardiovascular mortality compared to lower PMH levels. Further, one-third of the pollution-related risk of premature cardiovascular deaths was explained by increased burden of PMH.
Dr. Abohashem said: “Our results reveal a dual threat from air pollution: it not only worsens mental health but also significantly amplifies the risk of heart-related deaths associated with poor mental health. Public health strategies are urgently needed to address both air quality and mental wellbeing in order to preserve cardiovascular health.”
The levels of pollution across ESC countries can be viewed in the ESC Atlas of Cardiology:

References and notes
1The abstract ‘Air pollution associates with poor mental health and amplifies the premature cardiovascular death in the United States: longitudinal nationwide analysis’ will be presented during the session ‘Young Investigators Award — Population Science and Public Health’ which takes place on 26 April 2024.
2World Health Organization: Ambient (outdoor) air pollution.
3Byrne P. Meeting the challenges of rising premature mortality in people with severe mental illness. Future Healthc J. 2023;10(2):98-102.
4CDC PLACES databases.
5CDC Behavioral Risk Factor Surveillance System.
6CDC WONDER databases.
7The analyses were adjusted for calendar year and county characteristics such as demographics, median household income, unemployment rates, violent crime rates, education level, food environment index, rates of health insurance, level of mental health provision, level of primary care provision.

Read more →