Publisher Health

Artificial intelligence reduced by twofold the rate at which precancerous polyps were missed in colorectal cancer screening, reported a team of international researchers led by Mayo Clinic. The study is published in Gastroenterology.
Most colon polyps are harmless, but some over time develop into colon or rectal cancer, which can be fatal if found in its later stages. Colorectal cancer is the second most deadly cancer in the world, with an estimated 1.9 million cases and 916,000 deaths worldwide in 2020, according to the World Health Organization. A colonoscopy is an exam used to detect changes or abnormalities in the large intestine (colon) and rectum.
Between February 2020 and May 2021, 230 study participants each underwent two back-to-back colonoscopies on the same day at eight hospitals and community clinics in the U.S., U.K. and Italy. One colonoscopy used AI; the other, a standard colonoscopy, did not.
The rate at which precancerous colorectal polyps is missed has been estimated to be 25%. In this study, the miss rate was 15.5% in the group that had the AI colonoscopy first. The miss rate was 32.4 % in the group that had standard colonoscopy first. The AI colonoscopy detected more polyps that were smaller, flatter and in the proximal and distal colon.
“Colorectal cancer is almost entirely preventable with proper screening,” says senior author Michael B. Wallace, M.D., division chair of gastroenterology and hepatology at Sheikh Shakhbout Medical City in Abu Dhabi, United Arab Emirates and the Fred C. Andersen Professor of Medicine at Mayo Clinic in Jacksonville, Fla. “Using artificial intelligence to detect colon polyps and potentially save lives is welcome and promising news for patients and their families.”
In addition, false negative rates were 6.8% in the group that had the AI colonoscopy first. It was 29.6% in the group that had standard colonoscopy first. A false-negative result indicates that you do not have a particular condition, when in fact you do.
The study’s senior author and principal investigator is Michael B. Wallace, M.D., of Sheikh Shakhbout Medical City in Abu Dhabi, UAE and Mayo Clinic in Jacksonville, Fla. Co-authors include Cesare Hassan, M.D., Ph.D, of Nuovo Regina Margherita Hospital in Rome, Italy; James East, M.D., of John Radcliffe Hospital in Oxford, U.K., and Mayo Clinic Healthcare in London; Frank Lukens, M.D., of Mayo Clinic in Jacksonville, Fla.; Genci Babameto, M.D., of Mayo Clinic Health System in La Crosse, Wis.; Daisy Batista, M.D., of Mayo Clinic Health System in La Crosse, Wis.; Davinder Singh, M.D., of Mayo Clinic Health System in La Crosse, Wis.; William Palmer, M.D. of Mayo Clinic in Jacksonville, Fla.; Francisco C. Ramirez, M.D., of Mayo Clinic in Scottsdale, Ariz.; Tisha Lunsford, M.D., of Mayo Clinic in Scottsdale, Ariz.; Kevin Ruff, M.D., of Mayo Clinic in Scottsdale, Ariz.; David Cangemi, M.D., of Mayo Clinic in Jacksonville, Fla.; Gregory Derfus, M.D., of Mayo Clinic Health System in Eau Claire, Wis. Victor Ciofoaia, M.D., another co-author, was affiliated with Mayo during the study, but has since left Mayo.
Cosmo Artificial Intelligence-AI Ltd. funded the study.
Dr. Wallace has financial interests in Verily, Cosmo Pharmaceuticals, Fujifilm, Olympus and Virgo.
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Materials provided by Mayo Clinic. Original written by Rhoda Madson. Note: Content may be edited for style and length.

New research from Cornell scientists is exploring how human genetics impacts functions of the gut microbiome, and is expanding awareness of the role human genetics plays in shaping the microbiome.
The trillions of individual organisms constituting a person’s gut microbiome greatly impact metabolic function, disease and overall health. What has been less clear is how and to what extent the gut microbiome is, in turn, shaped by the genome of its human host.
Ilana Brito, assistant professor and Mong Family Sesquicentennial Faculty Fellow in the Nancy E. and Peter C. Meinig School of Biomedical Engineering, and her coauthors took a novel approach to examining host-microbiome genetic interactions and were able to show many instances where a human host’s genetic makeup directly affected the functional performance of the gut microbiome.
Their paper, “Collective Effects of Human Genomic Variation on Microbiome Function,” was published March 9 in the journal Scientific Reports. The study was a cross-college collaboration that combined Brito’s knowledge of the microbiome with faculty expertise in genetic variation and statistical methodology, respectively, from Andrew Clark, the Jacob Gould Schurman Professor of Population Genetics in the College of Arts and Sciences; and Martin Wells, the Charles A. Alexander Professor of Statistical Sciences in the Department of Information Science.
“When a disease or phenotype is caused by a single genetic mutation it can be a relatively straightforward process to find the gene responsible,” Brito said. But just as often, an entire suite of genes can interact to result in disease or other phenotypic expression, a much more complex mechanism. Within the human genome there are many sequential variations from person to person and even within paired chromosomes of the same person.
When a variation is produced by the substitution of a single nucleotide, this is called single nucleotide polymorphism (SNP). Using a unique computational and modeling approach, Brito’s team was able to identify SNPs that correlated with microbiome-associated traits, disorders and cancers. In other words, they were able to show direct effects of the human genome on the functions of the gut microbiome.

Legalization of recreational marijuana reduces demand for costly prescription drugs through state Medicaid programs, according to an analysis by a Cornell researcher and a collaborator.
When states legalize marijuana, the volume of prescriptions within the drug classes that align with the medical indications for pain, depression, anxiety, sleep, psychosis and seizures significantly decline, the researchers found.
Shyam Raman, a doctoral student in the Cornell Jeb E. Brooks School of Public Policy, and Indiana University doctoral student Ashley Bradford conducted the research. Their article, “Recreational Cannabis Legalizations Associated with Reductions in Prescription Drug Utilizations Among Medicaid Enrollees,” published April 15 in the journal Health Economics.
Most cannabis research has focused on the impact of medical marijuana on demand for prescription drugs or the impact of recreational use legalization on opioid demand. This is among the first studies to focus on the impact of legal personal-use cannabis on a broad range of prescription drugs.
“These results have important implications,” Raman said. “The reductions in drug utilization that we find could lead to significant cost savings for state Medicaid programs. The results also indicate an opportunity to reduce the harm that can come with the dangerous side effects associated with some prescription drugs.”
Raman and Bradford based their study on an analysis of data retrieved from the Centers for Medicare and Medicaid Services in all 50 states from 2011 to 2019, a period that saw growth in the number of states permitting personal use of marijuana.
About 40 states have legalized medical marijuana that must be prescribed by a doctor. So far, about 20 states have legalized personal-use cannabis for all adults, but that number is likely to rise. In those states, Raman and Bradford found a meaningful change in the demand for drugs used to treat sleep and anxiety disorders but no real impact on drugs used to treat nausea.
Raman and Bradford caution that cannabis use is not itself without harm, noting the many studies that associate it with a potential triggering of anxiety and psychoses such as schizophrenia. Also, patients who use marijuana to treat their medical conditions may be shifting away from visiting their doctor and therein creating discontinuities in primary care.
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Materials provided by Cornell University. Original written by Jim Hanchett, courtesy of the Cornell Chronicle. Note: Content may be edited for style and length.

Have you ever wondered if bacteria make distinctive sounds? If we could listen to bacteria, we would be able to know whether they are alive or not. When bacteria are killed using an antibiotic, those sounds would stop — unless of course the bacteria are resistant to the antibiotic. This is exactly what a team of researchers from TU Delft , led by dr. Farbod Alijani, now have managed to do: they captured low-level noise of a single bacterium using graphene. Now, their research is published in Nature Nanotechnology.
The sound of a single bacterium
Farbod Alijani’s team was originally looking into the fundamentals of the mechanics of graphene, but at a certain point they wondered what would happen if this extremely sensitive material comes into contact with a single biological object. “Graphene is a form of carbon consisting of a single layer of atoms and is also known as the wonder material,” says Alijani. “It’s very strong with nice electrical and mechanical properties, and it’s also extremely sensitive to external forces.”
The team of researchers initiated a collaboration with the nano biology group of Cees Dekker and the nanomechanics group of Peter Steeneken. Together with PhD student Irek Roslon and postdoc Dr. Aleksandre Japaridze, the team ran their first experiments with E. coli bacteria. Cees Dekker: “What we saw was striking! When a single bacterium adheres to the surface of a graphene drum, it generates random oscillations with amplitudes as low as a few nanometers that we could detect. We could hear the sound of a single bacterium!”
Punching a graphene drum with a bacterium
The extremely small oscillations are a result of the biological processes of the bacteria with main contribution from their flagella (tails on the cell surface that propel bacteria). “To understand how tiny these flagellar beats on graphene are, it’s worth saying that they are at least 10 billion times smaller than a boxer’s punch when reaching a punch bag. Yet, these nanoscale beats can be converted to sound tracks and listened to — and how cool is that,” Alijani says.
Graphene for fast detection of antibiotic resistance
This research has enormous implications for the detection of antibiotic resistance. The experimental results were unequivocal: If the bacteria were resistant to the antibiotic, the oscillations just continued at the same level. When the bacteria were susceptible to the drug, vibrations decreased until one or two hours later, but then they were completely gone. Thanks to the high sensitivity of graphene drums, the phenomenon can be detected using just a single cell.
Farbod Alijani: “For the future, we aim at optimizing our single-cell graphene antibiotic sensitivity platform and validate it against a variety of pathogenic samples. So that eventually it can be used as an effective diagnostic toolkit for fast detection of antibiotic resistance in clinical practice.” Peter Steeneken concludes: “This would be an invaluable tool in the fight against antibiotic resistance, an ever- increasing threat to human health around the world.”
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Materials provided by Delft University of Technology. Note: Content may be edited for style and length.

A person’s risk of developing diseases such as type 2 diabetes or breast cancer may be influenced by thousands of genetic differences. Looking at a single DNA difference that has a small effect on risk may not be clinically useful, but when hundreds or thousands of these small risks are added up into a single score, often called a polygenic risk score (PRS), they might offer clinically meaningful information about a person’s disease risk. In a new paper published in Nature Medicine, researchers from Brigham and Women’s Hospital, Veterans Affairs (VA) Boston Healthcare System, and Harvard Medical School developed and validated polygenic risk scores for six common diseases. The team also developed informational resources for each disease to help physicians and patients discuss how to incorporate PRS when making medical decisions about screening and prevention.
“As a primary care physician myself, I knew that busy physicians were not going to have time to take an entire course on polygenic risk scores,” said corresponding author Jason Vassy, MD, MPH, of the Brigham’s Division of General Internal Medicine & Primary Care, the Brigham’s Precision Population Health at Ariadne Labs and VA Boston. “Instead, we wanted to design a lab report and informational resources that succinctly told the doctor and patient what they need to know to make a decision about using a polygenic risk score result in their health care.”
Vassy and colleagues developed the risk scores as part of the Genomic Medicine at VA (GenoVA) Study, a randomized clinical trial of PRS testing among generally healthy adults. The study team developed and validated a laboratory test at the Mass General Brigham Laboratory for Molecular Medicine (LMM) for polygenic risk scores for atrial fibrillation, coronary artery disease, type 2 diabetes, breast cancer, colorectal cancer, and prostate cancer.
The GenoVA Study is currently enrolling patients at the VA Boston Healthcare System, and the investigators reported the results from the first 227 patients, among whom 11 percent were found to have a high polygenic risk score for atrial fibrillation, 7 percent for coronary artery disease, 8 percent for type 2 diabetes, and 6 percent for colorectal cancer. Among men, 15 percent had a high score for prostate cancer, while 13 percent of women had a high score for breast cancer. The GenoVA Study will ultimately enroll more than 1,000 patients and follow them for two years to observe how they and their primary care providers use the polygenic risk scores in clinical care. For example, high-risk patients might choose to undergo screening tests more frequently or take preventive medications that can lower their risk.
The researchers had to address many challenges in implementing a clinical laboratory PRS test. Most importantly, their own observations confirmed a problem that was already known about these scores: they are less accurate in individuals of non-European descent. Most genomic research to date has been conducted in European populations, thus the scores resulting from this research have a weaker ability to predict disease risk among non-European populations. Implementing a polygenic risk score into clinical care that is only accurate for people of European descent would exacerbate existing health disparities. To address this important limitation, the researchers applied additional statistical methods to enable PRS calculation across multiple racial groups.
“Researchers must continue working to increase the diversity of patients participating in genomics research,” said Matthew Lebo, PhD, Chief Laboratory Director at the LMM. “In the meantime, we were heartened to see that we could generate and implement valid genetic scores for patients of diverse backgrounds.”
To date, 52 percent of GenoVA Study enrollees report non-white race and/or Hispanic/Latinx ethnicity.
Another key challenge in bringing polygenic risk score to clinical medicine is that physicians and patients will need support to understand them and use them to make medical decisions. Clinical guidelines do not yet exist to help a physician know whether and how they should treat a patient with a high-risk score differently than an average-risk patient, but the study provides physician- and patient-oriented educational materials to help them incorporate the results. In addition, patients and primary care physicians can seek support from a genetic counselor in the study.
The researchers hope that this first report from the GenoVA Study will be a useful guide for other laboratories and health care systems looking to implement polygenic risk score testing in patient care. “It’s still very early days for precision prevention,” says Vassy, “but we have shown it is feasible to overcome some of the first barriers to bringing polygenic risk scores into the clinic.”
Funding: This work was supported by the NIH National Human Genome Research Institute (R35HG010706) and the NIH (R01HL139731, R01HL157635), American Heart Association (18SFRN34250007), National Heart, Lung and Blood Institute (R01HL142711, R01HL148050, R01HL151283, R01HL127564, R01HL148565, R01HL135242, R01HL151152), National Institute of Diabetes and Digestive and Kidney Diseases (R01DK125782), Fondation Leducq (TNE-18CVD04) and Massachusetts General Hospital (Fireman Chair).

The COVID-19 pandemic has led healthcare organizations to draft plans for critical patient care in the event of shortages of resources such as ventilators. Invoking “crisis-care” standards at a hospital would prompt the deployment of a triage team — three or four seasoned clinicians and a medical ethicist responsible to determine which patients have the best chance of survival and prioritizing these people to receive scarce resources while deprioritizing others.
If this task sounds tragic, you’re in good company: A new analysis conveys the moral distress that triage team members experienced while participating in a simulated crisis-care event in which they had to decide which patients would and would not be prioritized to receive life-sustaining resources.
The paper was published April 18 in JAMA Network Open.
“This was a setting to try to operationalize a process for making life-and-death patient decisions in a way that most medical professionals have never faced before,” said the paper’s lead author, Dr. Catherine Butler. She is an assistant professor of medicine (nephrology) at the University of Washington School of Medicine.
The qualitative analysis was based on interviews conducted from December 2020 to February 2021 with 41 triage-team members from hospitals in Washington state. They had participated in 12 patient simulations and their feedback informed the WA state Department of Health’s guidebook for critical care in response to potential extreme resource scarcity during the pandemic.
The intention of the guidebook, Butler said, is to provide plans based on empirical evidence and community deliberation that would standardize the triage process, improve fairness, and reduce the emotional toil involved in the grave deliberations for which triage team members might be unprepared.

DNA methylation is a major epigenetic modification that is crucial for mammalian development. For instance, DNA methylation is central to inexhaustible biological processes, such as gene regulation and cell fate decisions. In mammals, DNA methyltransferases are key for blastocysts to re-establish global DNA methylation patterns during implantation. This is critical for passing on epigenetic information to the next generation. On the other hand, the role of methyl-CpG binding proteins (MBPs) that bind methylated CpG as part of the DNA methylation processes is still unclear. However, a previous study conducted by researchers at Nara Institute of Science and Technology (NAIST), Japan, clarified that; Zbtb38, also known as CIBZ, is a zinc finger type of MBP that is pivotal for the growth of mouse embryonic stem (ES) cells. They further demonstrated that Zbtb38 facilitates the expression of Nanog, which is fundamental for the growth of ES cells. However, what Zbtb38 does in real life, is still a mystery.

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Noninvasive sound technology developed at the University of Michigan breaks down liver tumors in rats, kills cancer cells and spurs the immune system to prevent further spread — an advance that could lead to improved cancer outcomes in humans.
By destroying only 50% to 75% of liver tumor volume, the rats’ immune systems were able to clear away the rest, with no evidence of recurrence or metastases in more than 80% animals.
“Even if we don’t target the entire tumor, we can still cause the tumor to regress and also reduce the risk of future metastasis,” said Zhen Xu, professor of biomedical engineering at U-M and corresponding author of the study in Cancers.
Results also showed the treatment stimulated the rats’ immune responses, possibly contributing to the eventual regression of the untargeted portion of the tumor and preventing further spread of the cancer.
The treatment, called histotripsy, noninvasively focuses ultrasound waves to mechanically destroy target tissue with millimeter precision. The relatively new technique is currently being used in a human liver cancer trial in the United States and Europe.
In many clinical situations, the entirety of a cancerous tumor cannot be targeted directly in treatments for reasons that include the mass’ size, location or stage. To investigate the effects of partially destroying tumors with sound, this latest study targeted only a portion of each mass, leaving behind a viable intact tumor. It also allowed the team, including researchers at Michigan Medicine and the Ann Arbor VA Hospital, to show the approach’s effectiveness under less than optimal conditions.

From the muscle fibers that move us to the enzymes that replicate our DNA, proteins are the molecular machinery that makes life possible.
Protein function heavily depends on their three-dimensional structure, and researchers around the world have long endeavored to answer a seemingly simple inquiry to bridge function and form: if you know the building blocks of these molecular machines, can you predict how they are assembled into their functional shape?
This question is not so easy to answer. With complex structures dependent on intricate physical interactions, researchers have turned to artificial neural network models — mathematical frameworks that convert complex patterns into numerical representations — to predict and “see” the shape of proteins in 3D.
In a new paper published in Nature Communications, researchers at Georgia Tech and Oak Ridge National Laboratory build upon one such model, AlphaFold 2, to not only predict the biologically active conformation of individual proteins, but also of functional protein pairings known as complexes.
The work could help researchers bypass lengthy experiments to study the structure and interactions of protein complexes on a large scale, said Jeffrey Skolnick, Regents’ Professor and Mary and Maisie Gibson Chair in the School of Biological Sciences and one of the corresponding authors of the study, adding that computational models such as these could mean big things for the field.
If these new computational models are successful, Skolnick said, “it could fundamentally change the way biological molecular systems are studied.”
Primed for Protein Prediction

A new Michigan Medicine study finds that some children with cerebral palsy and scoliosis do not require pelvic fixation when undergoing growing rod treatment, potentially avoiding several complications.
Using data from around 20 health systems, researchers analyzed nearly 100 pediatric patients with cerebral palsy and scoliosis treated with growth-friendly implants, in which expandable rods are inserted into the back to help control the spinal curvature while still allowing the spine to grow. They found that for children with a pelvic tilt and lower lumbar spine tilt of fewer than 10 degrees, the pelvis did not need to be included when inserting growing rods. The results are published in Spine Deformity.
“Inserting screws into the pelvis to anchor the growing rods is not benign; screws in that area tend to be more prominent,” said G. Ying Li, M.D., lead author of the paper and pediatric orthopaedic surgeon at University of Michigan Health C.S. Mott Children’s Hospital.
“Prominent screws can be painful and can also cause overlying skin breakdown, leading to infection. In the past, there has also been a high rate of these screws failing. For these reasons, understanding which kids have enough of a tilt in their pelvis and lower lumbar spine to benefit from anchoring the rods into the pelvis is important.”
Children with cerebral palsy have abnormal nerve and muscle control, and many of them are wheelchair users. When they develop scoliosis, the curve in their spine tends to be longer and more sweeping than those without the condition. The curve may extend into the pelvis, affecting standing and sitting balance and causing pressure that can make sitting more painful or lead to skin breakdown.
Patients treated with growing rods require more than one surgery, and most children eventually need a spinal fusion. Growth-friendly treatment is already associated with more complications than a single spinal fusion. For patients with cerebral palsy who have a small enough pelvic tilt, Li says, it is beneficial to avoid inserting screws into the pelvis in the early stages of growth-friendly treatment.
“Even though we did see some children with growing rods anchored to the spine who later needed to have the rods anchored to the pelvis, we inserted those pelvic screws when kids were undergoing their final spinal fusion procedure,” she said.
“These findings provide fellow surgeons with more information to help patients avoid complications while still correcting a curve that can impact quality of life, pain and lung development for children with cerebral palsy.”
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Materials provided by Michigan Medicine – University of Michigan. Original written by Noah Fromson. Note: Content may be edited for style and length.