About a year ago, a friend of mine started evading my invitations to grab a drink. It was only when we caught up for a walk that she explained she wasn’t putting me off for any personal reason — it was just that she had stopped drinking. She wasn’t a heavy drinker — she had a glass of wine with dinner, the occasional Aperol spritz — but she’d been hearing on podcasts and reading in the news that even a small amount of alcohol was much worse for her health than had previously been understood. Listen to this article, read by Kirsten PotterMy friend was picking up on a swing in the public-health messaging around alcohol. For many years, she might have felt that she was making a healthy choice in having a glass of wine or a beer with dinner. Right around the time when she came of legal age to drink, the early 1990s, some prominent researchers were promoting, and the media helped popularize, the idea that moderate drinking — for women, a drink a night; for men, two — was linked to greater longevity. The cause of that association was not clear, but red wine, researchers theorized, might have anti-inflammatory properties that extended life and protected cardiovascular health. Major health organizations and some doctors always warned that alcohol consumption was linked to higher cancer risk, but the dominant message moderate drinkers heard was one of not just reassurance but encouragement.More recently, though, research has piled up debunking the idea that moderate drinking is good for you. Last year, a major meta-analysis that re-examined 107 studies over 40 years came to the conclusion that no amount of alcohol improves health; and in 2022, a well-designed study found that consuming even a small amount brought some risk to heart health. That same year, Nature published research stating that consuming as little as one or two drinks a day (even less for women) was associated with shrinkage in the brain — a phenomenon normally associated with aging.Drinking increased during the pandemic, which may be why news of any kind about alcohol seems to have found a receptive audience in recent years. In 2022, an episode of the podcast “Huberman Lab” that was devoted to elaborating alcohol’s various risks to body and brain was one of the show’s most popular of that year. Nonalcoholic spirits have gained such traction that they’ve started forming the basis for entire nightlife guides; and more people are now reporting that they consume cannabis than alcohol on a daily basis.Some governments are responding to the new research by overhauling their messaging. Last year, Ireland became the first country to pass legislation requiring a cancer warning on all alcohol products sold there, similar to those found on cigarettes: “There is a direct link between alcohol and fatal cancers,” the language will read. And in Canada, the government has revised its alcohol guidelines, announcing: “We now know that even a small amount of alcohol can be damaging to health.” The guidelines characterize one to two drinks a week as carrying “low risk” and three to six drinks as carrying “moderate risk.” (Previously the guidelines suggested that women limit themselves to no more than two standard drinks most days, and that men place that limit at three.)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.

A new state law will permit surgeons to perform cesarean deliveries in “advanced birth centers,” despite the risk of complications.A new law in Florida allowing doctors to perform cesarean sections in outpatient birthing centers has raised serious safety concerns among medical experts, who say the procedures carry a small but real risk of life-threatening complications and should not be undertaken outside hospitals.The proposed new facilities, to be called advanced birth centers, will not be able to rapidly mobilize extra staff, equipment and expertise should complications suddenly occur, as a hospital would, critics noted.“A pregnant patient who is considered low risk in one moment can suddenly need lifesaving care in the next,” said Dr. Cole Greves, the Florida district chairman for the American College of Obstetricians and Gynecologists.“Advanced birth centers, even with increased regulations, cannot guarantee the level of safety patients would receive within a hospital,” he said.Florida’s law, the first of its kind in the nation, comes as the United States grapples with a maternal mortality rate that far exceeds those of comparable high-income countries.Florida itself lags other states in maternal care, getting a D+ grade in a recent March of Dimes report because maternal outcomes for Black women are abysmal. The state has high rates of C-sections, and rates of preterm births and infant deaths are worse than the national average.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.

CRISPR/Cas9 gene editing has made possible a multitude of biomedical experiments including studies that systematically turn off genes in cancer cells to look for ones that the cancer cells heavily depend on to survive and grow. These genes, or “cancer dependencies,” are often promising drug targets. But new research shows that many of these CRISPR screening experiments rely on components, called CRISPR/Cas9 guides, that do not perform equally well in cells from people of all ancestries, which can cause CRISPR screens to miss cancer dependencies.
These CRISPR guides are short sequences of RNA that steer the CRISPR Cas9 enzyme to a specific site in the genome to cut DNA and deactivate a targeted gene. The new findings, from scientists at the Broad Institute of MIT and Harvard, show about 2 percent of these guides miss their target. This means that Cas9 won’t make a cut and disable a specific gene, thereby obscuring a potential role of that gene in cancer growth. The team found that this happens disproportionately in cells from people of African ancestry, because CRISPR guides were designed using reference genomes from people who are largely of European ancestry and do not fully represent global genetic diversity.
“These inaccuracies exist in places we might not recognize and in ways that we wouldn’t have predicted,” said Rameen Beroukhim, an associate member at the Broad and a co-senior author on the paper, which appeared recently in Nature Communications. “This work shows that it’s really worthwhile to conduct a systematic assessment of all the tools and datasets that we’re using so that we can fix these hidden biases before they become an issue.”
“CRISPR is used ubiquitously in preclinical research, but only a minority of researchers are thinking carefully about the specific germline and ancestries that relate to their model systems,” added Jesse Boehm, an associated scientist at the Broad and a co-senior author on the paper. “This is a warning call for the community that functional genomics is not immune to ancestry bias, and a source of opportunity to look more closely at this kind of data.”
In their study, the team analyzed data from the Broad’s Cancer Dependency Map (DepMap), the largest cancer dependency resource, which currently includes genome-wide screens in more than 1,000 cancer cell lines, about 90 percent of which are from people of European or East Asian descent.
Francisca Vazquez, director of the DepMap at the Broad, said that less than 1 percent of cell line-guide pairs in the DepMap are affected by the ancestry bias shown by this study, but that these biases are important to recognize and fix in future libraries. After these results were first posted as a preprint in 2022, the DepMap team removed from their library all guide RNAs that didn’t work, so that instead of falsely returning no dependencies for the affected genes, the database indicates that there is not sufficient data to draw conclusions.
A new kind of dependency search
Previously, the search for cancer dependencies focused on genetic changes that arise in some cells during a person’s life, called somatic mutations. But when postdoctoral researcher and study first author Sean Misek joined Boehm’s and Beroukhim’s labs in 2020, he wanted to know how germline genetic variants — which are inherited and in all cells throughout the body — influence how tumors respond to treatment.

Misek found many strong associations between ancestry and genetic dependencies, and that most of those associations came from artifacts related to germline variants. In particular, he saw these effects in CRISPR guides. The sequence of the guide RNAs didn’t sufficiently match the target genetic sequence because that target sequence varied depending on ancestry.
The scientists found that 89 percent of guides in genome-scale libraries have a mismatch in at least one cell line. They also found that mismatches occur to a greater degree in cells from people of African ancestry.
“These sorts of experimental biases are probably everywhere in preclinical research,” Misek said. “We hope that this paper is part of a larger conversation.”
Understanding the extent of this bias in a research project can be challenging for a scientist because it can take several days to download all the necessary data to do so. To address this, Boehm, Beroukhim, and the Pattern team at the Broad built Ancestry Garden, a website based on data from the Genome Aggregation Database (gnomAD) that can help researchers determine the effect of ancestry on a guide of their choosing.
“A lot of labs use CRISPR in some sense, and they should have a mechanism to check their reagents,” Misek said. “Our goal is to make it a little bit easier for people to mitigate this issue in their own hands.”
Library lessons
Boehm said that genetic variation due to ancestry affects research far beyond the search for cancer dependencies, and that the extent to which the team’s findings will impact individual studies will vary. Although the effect of this bias was relatively modest in the DepMap, it may be much larger in experiments that study only one or a small number of cell lines, Boehm said.
Going forward, the study team and DepMap researchers say that an important way to address this bias is to increase the genetic diversity in large-scale cell line libraries. “We encourage the community to send us cell lines from under-represented populations if they have them,” Vazquez said. “This is a very important issue to address.”

Researchers have consistently shown that prenatal exposure to Di (2-ethyhexyl) phthalate harms the reproductive system in male mice and causes fertility defects. In a new study, scientists from the University of Illinois Urbana-Champaign have shown that the combination of DEHP and a high-fat diet in pregnant mice can cause more damage to pups than each factor alone.
Male reproductive disorders are a growing issue due to the global decrease in sperm count and quality. Concerningly, chemicals like DEHP, which can be found in food storage containers, pharmaceuticals, and building materials, have been found to be one of the contributing factors. The toxicity of DEHP is due to its ability to mimic the hormones in our bodies, leading to long-term effects on health.
“The scientific community is aware of the fact that the current generation of men produce half as much sperm compared to the previous one,” said CheMyong Jay Ko (EIRH), a professor of veterinary medicine. “Although it is shocking, not much attention is paid to understanding the causes.”
The researchers used the Barker hypothesis as a guiding principle for their study. Proposed by the British physician and epidemiologist David Barker, the hypothesis argued that the nine months in utero are one of the most critical periods in a person’s life and can shape their future health trajectories.
“The Barker hypothesis primarily focuses on nutrition and we wanted to test whether the mother’s diet could change the health of the next generation,” Ko said. “Additionally, unlike the previous generation, we are constantly exposed to chemicals like DEHP, which can alter how our bodies function. We wanted to ask whether the exposure to both these factors can cause growing babies to have lesser functioning reproductive systems.”
In the past, both the Ko lab and other research groups have shown that prenatal exposure to DEHP decreases testosterone levels and causes fertility defects in male mice. Additionally, scientists have shown that maternal high-fat diet can also decrease sperm counts in male offspring. However, the effects of both together had not been studied.
The researchers used four groups of pregnant mice; one was a control and the other three were either exposed to DEHP, or a high-fat diet, or a combination of the two. They then followed each litter, which contained an average of 6 male and 6 female pups.
“Surprisingly, we found that a high-fat diet had a more damaging effect on the male reproductive systems compared to DEHP alone and the pups born from mothers who had been treated with both had the worst outcomes,” Ko said.
The researchers measured the weight of the body and different reproductive organs in pups during different stages of growth and puberty. They found that although the body weight of pups born from moms on a high-fat diet alone or in combination with DEHP was higher than the other pups, the weight of the reproductive organs was lower. They also found that these mice produced less sperm and had lower testosterone levels. By staining the tissues, the researchers found that the reproductive organs had abnormal cells, which were contributing to the gonadal dysfunction.
“In our studies, we used these mice as a model. Although we need to confirm these results in humans, this study should serve as a warning to our generation that we need to be careful about our environment and diet during pregnancy,” Ko said.

The innate immune system is responsible for protecting the human body from threats that could cause disease or infection. The system relies on innate immune sensors to detect and transmit signals about these threats. One of the key innate immune strategies to respond to threats is through cell death. New research from St. Jude Children’s Research Hospital discovered that NLRC5 plays a previously unknown role as an innate immune sensor, triggering cell death. The findings, published in Cell, show how NLRC5 drives PANoptosis, a prominent type of inflammatory cell death. This understanding has implications for the development of therapeutics that target NLRC5 for the treatment of infections, inflammatory diseases and aging.
Depending on the threat, innate immune sensors can assemble complexes such as inflammasomes or PANoptosomes. The inflammasome can be thought of like an emergency broadcast system that is activated quickly, while the PANoptosome is more like an emergency response unit that generally integrates more signals and components to respond to the threat. How innate immune sensors work — what triggers them to act — has been a mystery, which researchers have been chipping away at for decades.
Nucleotide-binding oligomerization domain-like receptors (NLRs) are a large family of important molecules involved in inflammatory signaling. They are generally thought to function as innate immune sensors that detect threats. However, the specific roles of several NLRs in sensing are not yet understood. Scientists at St. Jude conducted a large screen, testing a specific NLR, NLRC5, to see what threats activate it. Through their efforts, they discovered that depletion of nicotinamide adenine dinucleotide (NAD), a molecule essential in energy production, triggers NLRC5-mediated cell death through PANoptosis.
“One of the biggest questions in the fields of immunology and innate immunity is what the various members of the NLR family are sensing, and what their functions are,” said corresponding author Thirumala-Devi Kanneganti, PhD, St. Jude Department of Immunology vice chair. “NLRC5 was an enigmatic molecule, but now we have the answer — it is acting as an innate immune sensor and cell death regulator, driving inflammatory cell death, PANoptosis, by forming a complex.”
Identifying the NLRC5 trigger
Scientists in the Kanneganti lab conducted a rigorous screen to get to the bottom of what threats trigger NLRC5. This included looking at pathogens such as bacteria and viruses, as well as pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs) that can be released by or mimic an infection or the cause of an injury or illness, as well as other danger signals such as cytokines (immune signaling molecules).
The researchers also looked at heme, the component of hemoglobin responsible for carrying oxygen. Infections or disease can cause red blood cells to rupture in a process called hemolysis. This releases hemoglobin into the bloodstream. When hemoglobin breaks down into its components, it releases free heme, which is known to cause significant inflammation and organ damage. The researchers tested many different combinations of pathogens, PAMPs and DAMPs to see if NLRC5 was required for a response.

“Among all the combinations we tested, we identified that the combination of heme plus PAMPs or cytokines specifically induces NLRC5-dependent inflammatory cell death, PANoptosis,” said co-first author Balamurugan Sundaram, PhD, St. Jude Department of Immunology. “Our results showed for the first time that NLRC5 is central to responses to hemolysis, which can occur during infections, inflammatory diseases and cancers.”
Energy depletion triggers NLRC5 function
Upon identifying the heme-containing PAMP, DAMP and cytokine combinations that trigger NLRC5-dependent inflammatory cell death, the researchers further investigated how NLRC5 is regulated. They found that NAD levels drive NLRC5 protein expression. If NAD is depleted, that sounds an alarm that there is a threat the immune system should recognize. The researchers found that depletion of NAD is sensed by NLRC5, triggering PANoptosis.
“By supplementing with the NAD precursor, nicotinamide, we reduced NLRC5 protein expression and PANoptosis,” said co-first author Nagakannan Pandian, PhD, St. Jude Department of Immunology. “Therapeutically, nicotinamide has been widely studied as a nutrient supplement, and our findings suggest it could be helpful in treating inflammatory diseases.”
The researchers also discovered that NLRC5 is in an NLR network with NLRP12, which come together with other cell death molecules and form an NLRC5-PANoptosome complex that triggers inflammatory cell death. The finding builds on previous research by the Kanneganti lab showcasing the role of NLRP12 in PANoptosis.
A promising target for therapeutic development
NLRs are associated with diseases related to infection, inflammation, cancers and aging. This makes them intriguing targets for the development of novel therapeutics. The work of the Kanneganti lab shows that deleting Nlrc5 can provide protection against inflammatory cell death through PANoptosis and prevent disease pathology in hemolytic and inflammatory disease models, making NLRC5 an exciting therapeutic prospect.

“The fundamental knowledge that we have gained into how innate immune sensing works can be translated to numerous diseases and conditions,” Kanneganti said. “Aging, infectious disease, inflammatory disorders — things for which there are no targeted therapies, this could be an option.”
Authors and funding
The study’s other authors are Emily Alonzo, Department of Research and Development at Cell Signaling Technology; and Hee Jin Kim, Hadia Abdelaal, Omkar Indari, Roman Sarkar, Rebecca Tweedell, Jonathan Klein, Shondra Pruett-Miller and Peter Vogel, all of St. Jude, and Raghvendra Mall, formerly of St. Jude now of the Technology Innovation Institute, Abu Dhabi.
The study was supported by grants from the National Institutes of Health (AI101935, AI124346, AI160179, AR056296 and CA253095) and ALSAC, the fundraising and awareness organization of St. Jude.

In a message to the public, Catherine said she would attend King Charles’s birthday parade this weekend and wrote candidly about “knowing I am not out of the woods yet.”Catherine, the Princess of Wales, said on Friday that she planned to take part in a parade on Saturday marking the birthday of King Charles III, a tentative return to the public stage after confirming in March that she was being treated for cancer.The news, which Catherine released in a highly personal six-paragraph statement, reflected both the progress she has made since she was first hospitalized for abdominal surgery last January and the long road to recovery she still faces.“I am making good progress, but as anyone going through chemotherapy will know, there are good days and bad days,” Catherine wrote.“On those bad days you feel weak, tired and you have to give in to your body resting,” the princess said. “But on the good days, when you feel stronger, you want to make the most of feeling well.”Catherine, 42, said that she hoped to take part in a few other public engagements during the summer. But the princess, who has not been seen in public since last Christmas Day, emphasized that her appearance in the parade on Saturday — her first in several months — did not represent a formal return to public life.“I am not out of the woods yet,” she wrote. “I am learning how to be patient, especially with uncertainty. Taking each day as it comes, listening to my body, and allowing myself to take this much needed time to heal.”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.

Researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, have developed a new nanomedicine therapy that delivers anticancer drugs to lung cancer cells and enhances the immune system’s ability to fight cancer. The team showed promising results for the new therapy in cancer cells in the lab and in mouse lung tumor models, with potential applications for improving care and outcomes for patients with tumors that have failed to respond to traditional immunotherapy. Their findings are published in Science Advances.
“Nanoparticles have been used for years to deliver targeted medication to tumor cells, while immunotherapy has also had a paradigm-shifting impact on how we treat cancer, by stopping cancer cells from evading our immune system,” said lead author Tanmoy Saha, PhD, an instructor of medicine and researcher in the Division of Engineering in Medicine at the Brigham. “Here, we’ve essentially connected these two approaches in one drug delivery system to treat non-small cell lung cancer.”
Lung cancer is the leading cause of cancer death globally, accounting for over a quarter of all cancer-related deaths. Non-small cell lung cancer (NSCLC) is the most common form, making up roughly 85 percent of all lung cancer cases. One of the popular treatment methods for NSCLC is to use immune checkpoint inhibitors, a class of drugs that block certain proteins that stop the immune system from killing cancer cells. However, most patients with NSCLC do not respond to these drugs, primarily because the treatment only targets one protein (most commonly PD-L1), and that is not abundantly expressed in most lung cancer tumors. As a result, many patients must undergo a combination of chemo and immunotherapies, resulting in enduring side effects and toxicities.
This new therapy works by bringing a nanoparticle filled with a cancer-fighting drug straight to the tumor site, while antibodies attached to the nanoparticle bind to two different proteins (CD47 and PD-L1) on cancer cells. This dual approach allows both the innate and adaptive immune systems to locate and destroy cancer cells while minimizing the toxicities commonly associated with existing cancer treatments.
“This system operates with a kind of Velcro effect. Rather than just looking for one protein on a cancer cell that the antibody can grab onto, these nanoparticles have two,” said senior author Shiladitya Sengupta, PhD, an associate professor of medicine and bioengineer in the Division of Engineering in Medicine at the Brigham. “So, if a cancer cell does not express one of the proteins that our nanoparticle targets, it can still attach to the other one, and deliver the drug loaded into the nanoparticle straight to the cancerous tissue.”
The researchers set out to find which proteins were expressed by lung tumors. They screened more than 80 human lung cancer patients’ tissue. Once the proteins were identified, they selected antibodies to target them. Next, they functionalized the antibodies with a nanoparticle that was already loaded with an anticancer drug.
Saha and his colleagues then tested the nanoparticle’s efficacy by first visualizing how well the antibodies bound to cancerous cells in the lab. They performed a series of experiments to assess and visualize the nanoparticle’s binding and drug delivery capabilities. Subsequently, they tested the complex’s efficacy in mouse models of two forms of lung cancer. They found that the mice’s cancer cells internalized the drug, leading to a decrease in tumor size without any major side effects or toxicities.
The study’s limitations include that, so far, the therapy has only been tested on human tissue in the lab and in mouse models. It must undergo much more exhaustive toxicology studies before moving on to clinical testing. Looking ahead, the researchers hope to adapt this technology to treat other types of cancer by exploring additional antibodies and treatments that could work with this nanomedicine approach.
“While we are seeing some success with this drug delivery platform in preclinical testing, it’s important to remember that mouse and human physiology are quite different. We need more studies before we can bring this concept to clinical trials, but we’re excited to see how this approach could transform cancer care,” said Saha.

Each time the heart beats, it pumps blood through the brain vessels, causing them to expand slightly and then relax, much like the rise and fall of the blood pulsing through your veins when you feel your pulse in your wrist. This pulsation in the brain helps distribute blood evenly across different areas of the brain, ensuring that all parts receive the oxygen and nutrients they need to function properly. In healthy vessels, the pulse wave is dampened before it reaches the smallest vessels, where high pulsatility could be harmful. This new metric provides a comprehensive measure of the small vessel pulsatility risk.
A paper just published in Scientific Reports- Nature by Sergio Dempsey as first author with colleagues Dr Soroush Safaei, Dr Gonzalo Maso Talou at Auckland Bioengineering Institute, along with co-author Dr Holdsworth (Mātai and FMHS & CBR at the University of Auckland), describes the new metric based on 4D flow MRI technology.
This innovative metric is particularly crucial because increased vascular pulsatility is linked to several brain conditions, including Alzheimer’s disease and other forms of dementia. By accurately measuring how pulsatility is transmitted in the brain, researchers can better understand the underlying mechanism of these diseases and potentiall guide development f new treatments.
Current MRI methods face limitations due to anatomical variations and measurement constraints. The new technique removes this issue by integrating thousands of measurements across all brain vessels, rather than looking one spot at a time as the traditional methods. This provides a richer metric representative of the entire brain.
“The ability to measure how pulsatility is transmitted through the brain’s arteries could revolutionise our approach to neurological diseases, and support research in vascular damage hypotheses” explained Mr. Dempsey. “Our method allows for a detailed assessment of the brain’s vascular health, which is often compromised in neurodegenerative disorders.”
The study also highlighted the potential to enhance clinical assessments and research on brain health. By integrating this new metric into routine diagnostic procedures, healthcare providers can offer more precise and personalised care plans for individuals at risk of or suffering from cognitive impairments.
In addition to its implications for patient care, the researchers have made their tools publicly available, integrating them into pre-existing open-source software. This enables scientists and clinicians worldwide to adopt the advanced methodology, fostering further research and collaboration in the field of neurology.
The research team is planning further studies to explore the applications of this technique in larger and more diverse populations, beginning with the “Digital Twin Dementia Study” starting at Mātai later this month. Results from the initial study of the metric also identified important sex differences in vascular dynamics which has initiated a new study focussing on sex-related dynamics which is anticipated to begin at Mātai and the Centre for Advanced MRI (CAMRI) in November.

Scientists from the University of Groningen (the Netherlands), together with colleagues from the University of Montpellier (France) and the University of Oldenburg (Germany), have tested how a fever could affect the development of antimicrobial resistance. In laboratory experiments, they found that a small increase in temperature from 37 to 40 degrees Celsius drastically changed the mutation frequency in E. coli bacteria, which facilitates the development of resistance. If these results can be replicated in human patients, fever control could be a new way to mitigate the emergence of antibiotic resistance. The results were published in the journal JAC-Antimicrobial Resistance.
Antimicrobial resistance of pathogens is a worldwide problem, and recognized by the WHO as one of the top global public health and development threats. There are two ways to fight this: by developing new drugs, or by preventing the development of resistance. ‘We know that temperature affects the mutation rate in bacteria’, explains Timo van Eldijk, co-first author of the paper. ‘What we wanted to find out was how the increase in temperature associated with fever influences the mutation rate towards antibiotic resistance.’
Three antibiotics
‘Most studies on resistance mutations were done by lowering the ambient temperature, and none, as far as we know, used a moderate increase above normal body temperature,’ Van Eldijk reports. Together with Master’s student Eleanor Sheridan, Van Eldijk cultured E. coli bacteria at 37 or 40 degrees Celsius, and subsequently exposed them to three different antibiotics to assess the effect. ‘Again, some previous human trials have looked at temperature and antibiotics, but in these studies the type of drug was not controlled.’ In their laboratory study, the team used three different antibiotics with different modes of action: ciprofloxacin, rifampicin, and ampicillin.
The results showed that for two of the drugs, ciprofloxacin and rifampicin, increased temperature led to an increase in the mutation rate towards resistance. However, the third drug, ampicillin, caused a decrease in the mutation rate towards resistance at fever temperatures. ‘To be certain of this result, we actually replicated the study with ampicillin in two different labs, at the University of Groningen and the University of Montpellier, and got the same result,’ says Van Eldijk.
Fever-suppressing drugs
The researchers hypothesized that a temperature dependence of the efficacy of ampicillin could explain this result, and confirmed this in an experiment. This explains why ampicillin resistance is less likely to arise at 40 degrees Celsius. ‘Our study shows that a very mild change in temperature can drastically change the mutation rate towards resistance to antimicrobials,’ concludes Van Eldijk. ‘This is interesting, as other parameters such as the growth rate do not seem to change.’
If the results are replicated in humans, this could open the way to tackling antimicrobial resistance by lowering the temperature with fever-suppressing drugs, or by giving patients with a fever antimicrobial drugs with higher efficacy at higher temperatures. The team concludes in the paper: ‘An optimized combination of antibiotics and fever suppression strategies may be a new weapon in the battle against antibiotic resistance.’

An artificial intelligence-powered method for detecting tumor DNA in blood has shown unprecedented sensitivity in predicting cancer recurrence, in a study led by researchers at Weill Cornell Medicine, NewYork-Presbyterian, the New York Genome Center (NYGC) and Memorial Sloan Kettering Cancer Center (MSK). The new technology has the potential to improve cancer care with the very early detection of recurrence and close monitoring of tumor response during therapy.
In the study, which appears June 14 in Nature Medicine, the researchers showed that they could train a machine learning model, a type of artificial intelligence platform, to detect circulating tumor DNA (ctDNA) based on DNA sequencing data from patient blood tests, with very high sensitivity and accuracy. They made successful demonstrations of the technology in patients with lung cancer, melanoma, breast cancer, colorectal cancer and precancerous colorectal polyps.
“We were able to achieve a remarkable signal-to-noise enhancement, and this enabled us, for example, to detect cancer recurrence months or even years before standard clinical methods did so,” said study co-corresponding author Dr. Dan Landau, a professor of medicine in the division of hematology and medical oncology at Weill Cornell Medicine and a core faculty member of the New York Genome Center.
The study’s co-first author, and co-corresponding author, was Dr. Adam Widman, a postdoctoral fellow in the Landau Lab who is also a breast cancer oncologist at MSK. The other co-first authors were Minita Shah of NYGC, Dr. Amanda Frydendahl of Aarhus University, and Daniel Halmos of NYGC and Weill Cornell Medicine.
Liquid biopsy technology has been slow to realize its great promise. Most approaches to date have targeted relatively small sets of cancer-associated mutations, which are often too sparsely present in the blood to be detected reliably, resulting in cancer recurrences that go undetected.
Several years ago, Dr. Landau and colleagues developed an alternative approach based on whole-genome-sequencing of DNA in blood samples. They showed that they could gather much more “signal” this way, enabling more sensitive — and logistically simpler — detection of tumor DNA. Since then, this approach has been increasingly adopted by liquid biopsy developers.
In the new study, the researchers leapt ahead again, using an advanced machine learning strategy (similar to that of ChatGPT and other popular AI applications) to detect subtle patterns in sequencing data — in particular, to distinguish patterns suggestive of cancer from those suggestive of sequencing errors and other “noise.”
In one test, the researchers trained their system, which they call MRD-EDGE, to recognize patient-specific tumor mutations in 15 colorectal cancer patients. Following the patients’ surgery and chemotherapy, the system predicted from blood data that nine had residual cancer. Five of these patients were found — months later, with less sensitive methods — to have cancer recurrence. But there were no false negatives: none of the patients MRD-EDGE deemed free of tumor DNA experienced recurrence during the study window.

MRD-EDGE showed similar sensitivity in studies of early-stage lung cancer and triple-negative breast cancer patients, with early detection of all but one recurrence, and tracking of tumor status during treatment.
The researchers demonstrated that MRD-EDGE can detect even mutant DNA from precancerous colorectal adenomas — the polyps from which colorectal tumors develop.
“It had not been clear that these polyps shed detectable ctDNA, so this is a significant advance that could guide future strategies aimed at detecting premalignant lesions,” said Dr. Landau, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and a hematologist/oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
Lastly, the researchers showed that even without pre-training on sequencing data from patients’ tumors, MRD-EDGE could detect responses to immunotherapy in melanoma and lung cancer patients — weeks before detection with standard X-ray-based imaging.
“On the whole, MRD-EDGE addresses a big need, and we’re excited about its potential and working with industry partners to try to deliver it to patients,” Dr. Landau said.
The research in this story was supported in part by the National Cancer Institute, part of the National Institutes of Health, through grant number R01 CA266619.