Bouts of moderate-to-vigorous intensity exercise could improve the efficacy of antibody therapies used to treat chronic lymphocytic leukaemia, new research has shown.
Researchers at the Universities of Birmingham and Bath found that a bout of exercise increased the number of anti-cancer immune cells — called natural killer cells — and that these cells were around twice as effective at killing cancer cells in ‘ex vivo’ tests carried out on blood samples from patients.
In addition, the researchers found that the number of cancer cells present in blood samples transiently increased immediately after exercise — making them more susceptible to attack by natural killer cells and the antibody therapy.
The research, funded by Cancer Research UK, could hold promise for antibody therapy treatment for some forms of cancer, although more work is needed to determine the ‘in vivo’ effects in patients undergoing treatment.
Dr James Turner, a co-author on the study at the University of Birmingham, said: “These findings show a potential benefit to patients undergoing a very particular type of treatment and could open up new avenues of research to determine whether exercise can improve the way other cancer treatments work.”
In the study, published in Brain Behaviour and Immunity, the researchers wanted to test the effects of exercise on an antibody therapy called Rituximab. It is a common treatment for chronic lymphocytic leukaemia, which is a cancer of white blood cells, and is the second most common adult blood cancer in the UK. The therapy works by attaching itself to a specific protein on the surface of cancer cells, which natural killer cells are able to recognise and attack.
The researchers worked with 20 people between the ages of 45 and 82 who were diagnosed with chronic lymphocytic leukaemia but had not yet begun treatment. Participants were asked to do a 30 minute bout of moderate-to-vigorous intensity cycling. Blood samples were taken before and immediately after the exercise bout, and then a third sample was taken an hour later.

In the blood samples, under ‘ex vivo’ conditions, the researchers measured the number of natural killer cells present at each of the sample points and tested their ability to kill cancer cells with and without Rituximab present.
They found the number of natural killer cells increased by 254% after exercise and that in the blood samples taken after exercise, there were 67% more cancer cells compared to blood before exercise.
Next, the team isolated natural killer cells and put them in close contact with cancer cells for 2 hours ‘ex vivo’ with and without the antibody therapy Rituximab. When Rituximab was also present in the blood sample, natural killer cells were just over twice as effective in killing the cancer cells in the samples collected immediately after exercise compared to before.
Dr John Campbell, senior author of the study at the University of Bath said: “Cancer cells often try to ‘hide’ in the body but it seems that exercise works to move them out into the bloodstream, where they are vulnerable to the antibody therapy and the killing capabilities of natural killer cells.”
The results of the study could also have potential for patients who have finished their treatment for leukaemia and are in a monitoring phase in case cancer cells re-appear.
Dr Harrison Collier-Bain, first author of the study at the University Bath said: “Monitoring patients after treatment is complicated because if cancer cells remain or reappear, they are sometimes too low to detect, but a bout of exercise followed by a blood sample immediately afterwards could help to ‘find’ them if they are ‘hiding’ in the body.”
While these results are promising, larger-scale trials would needed in a cohort of patients undergoing Rituximab treatment before treatment recommendations could be made.

Caroline Geraghty, Senior Specialist Information Nurse at Cancer Research UK, said:
“This study adds to a growing body of evidence showing that exercise can be helpful before, during and after cancer treatment. We know that being physically active before and after treatment can help cancer patients cope better with treatment, aid recovery and improve mental wellbeing. It is interesting to see that exercise could also improve the efficacy of treatment for some types of blood cancer, although more research in a larger group of patients is needed.
“Everyone has different needs and abilities, so it’s important that you discuss with your doctor what forms of exercise would work best for you. We encourage all cancer patients to seek their doctor’s advice before starting a programme of exercise before or after treatment, to make sure that the activities suggested are appropriate for them.”

A study which examines the common skin condition, chronic spontaneous urticaria (CSU), characterised by recurrent hives, has been recently published by Trinity College Dublin researchers in the journal Allergy. This study is the first of its kind to show a link between rare cell types and treatment response. Professor Niall Conlon, Clinical Professor, School of Medicine and Consultant Immunologist, St James’s Hospital and Clinical Lead at Ireland’s only UCARE centre for urticaria management led the research team.
Chronic spontaneous urticaria (CSU) is a common but underreported disease, where individuals develop recurrent, unpredictable and intensely itchy hives and skin swellings with no obvious trigger. The UCARE centre at St. James’s Hospital sees 10-20 new patients with CSU per week. Although CSU shares some symptoms with food allergy, it is not caused by an allergy to food or medicines. Diagnosis of CSU can be late and difficult, due to a lack of awareness about the condition. Furthermore, individuals with this disease can become distressed and experience many frustrations ranging from difficulties at work and interpersonal relationships, to problems with sleep disturbance, low mood, and anxiety.
The study explored a rare form of mast cells called myeloid progenitors in blood, in patients with the condition. The team compared these cells in people with CSU and healthy controls. Treatment response to the anti-IgE therapy omalizumab, was also assessed. Individuals who had a fast response to omalizumab were found to have higher numbers of myeloid progenitors in their blood when compared to people who had a slow (or no) response, to omalizumab.
The study therefore points to the intriguing possibility of using these cell types to predict who might respond to treatment with anti-IgE therapies.
Dr Barry Moran, a scientist at Trinity Biomedical Science Institute (TBSI), Trinity College who contributed to the study said:
‘We developed a flow assay to identify this rare cell type. We were excited to find that our findings and clinical correlates were complemented by transcriptomic data’.
David McMahon from the Irish Skin Foundation said:
“CSU refers to hives that come and go, without any particular or obvious trigger, and last for longer than 6 weeks. For some people affected by CSU the quality of life impacts can be profound and far reaching.”

CSU is frequently mistaken for an allergic reaction. Specific triggers such as allergic reactions to foods are often sought. Unfortunately, attempts to avoid suspected allergic triggers do not help. This can be frustrating for people who suffer with this condition.
Symptoms for many people with CSU can be completely controlled by regular treatment with antihistamines. Often, these medications need to be used at high doses. Some individuals will not respond to this simple intervention and will need referral to a specialist centre such as the UCARE centre in St. James’s Hospital. Individuals who do not respond to high dose antihistamines are considered for the anti-IgE biologic treatment, omalizumab. This treatment is only available in a specialist setting.
Dr Conor Finlay, a scientist from the Trinity Translational Medicine Institute (TTMI) and one of the senior authors of the study, said:
“Mast cells pack a punch, when activated by IgE antibodies they can be said to explode and release inflammatory factors into the skin — this is what causes itching and hives.”
Dr Niall Conlon a senior author on the study and consultant immunologist: said:
“For somepeople, treatment with omalizumab, an injectable drug that steadies mast cells, really works. However, for others this drug is less effective or takes much longer to work. It would really help us to understand better why certain people don’t respond as well to omalizumab. Information on how this happens might help us direct our treatments more effectively and make patients better, quicker”
Dr Katie Ridge, the lead author on the study said:

“Mast cells are tricky cells to study. Mature mast cells are not found in the blood. That is why we used a method to study an extremely rare immature form of mast cells in the blood, called mast cell progenitors. Our findings point to potential inflammatory signals in this disease and highlight how chronic urticaria is more than skin deep.
“Our findings have significant implications not only in relation the individuals with urticaria but potentially other allergic diseases whereby we may be able to predict treatment response using exploration of this cell type. “

In a recent study, researchers from Helmholtz Munich and the Augsburg University Hospital show that nocturnal heat significantly increases the risk of stroke. The findings can contribute to the development of preventive measures: With them, the population can better protect themselves against the risks of climate change with increasingly frequent hot nights. In addition, knowledge of the consequences of hot nights can improve patient care.
Climate change is resulting in more and more extreme weather events. These include extremely hot, so-called tropical nights. The research team led by Dr. Alexandra Schneider investigated the effects of night-time heat on the risk of stroke. “We wanted to understand the extent to which high night-time temperatures pose a health risk,” says the head of the working group Environmental Risks at Helmholtz Munich. “This is important because climate change is causing night-time temperatures to rise much faster than daytime temperatures.”
Data on 11,000 strokes from 15 years
In their study, the researchers analyzed data from Augsburg University Hospital. Its Department of Neurology has collected data on around 11,000 strokes over 15 years. The analysis shows that extreme heat at night increases the risk of stroke by seven percent. “Elderly people and women are particularly at risk, and it is mainly strokes with mild symptoms that are diagnosed in clinics after hot nights,” says the study’s lead author, Dr. Cheng He: “Our results make it clear that adjustments in urban planning and the healthcare system are extremely important to reduce the risks posed by rising night-time temperatures.” This is all the more true as “we were able to show that the risk of stroke associated with high night-time temperatures increased significantly in the period 2013 to 2020 compared to the period 2006 to 2012,” as Prof. Michael Ertl, head of the Stroke Unit and the neurovascular working group at Augsburg University Hospital, emphasizes. From 2006 to 2012, hot nights resulted in two additional strokes per year in the study area; from 2013 to 2020, there were 33 additional cases per year.
Recommendations for adaptation strategies and urban planning
The researchers plan to make their findings applicable in practical settings. To this end, they are working on recommendations for public adaptation strategies and urban planning, such as reducing the intensity of urban heat islands. The aim is to better protect the population from the effects of night-time heat. The study will also serve as a basis for further research to develop targeted preventive measures against stroke-promoting factors. “The earlier these preventive measures are implemented, the better,” says Alexandra Schneider. The results of the study are also of great importance for hospitals. They will be able to better adapt to the frequency of strokes in the future: If the weather forecast predicts a hot night, it can be expected that more cases will come to the clinics. This allows clinics to provide more staff to care for patients as a precaution, explains Prof. Markus Naumann, Director of the Neurological University Hospital in Augsburg.
Background: What are tropical nights?
“Tropical nights” are defined using the so-called “Hot Night Excess Index” (HNE). It measures how much temperatures rise above a certain threshold value at night. The threshold value is the temperature that is only exceeded on the five percent warmest nights during the entire study period. In this study, this value is 14.6 °C. If temperatures rise above this value at night, this is categorized as a tropical night. The HNE index adds up how many degrees the temperatures are above this threshold during the night hours to determine the intensity of the heat.

A World Health Organization Essential Medicine, ketamine is widely used at varying doses for sedation, pain control, general anesthesia and as a therapy for treatment-resistant depression. While scientists know its target in brain cells and have observed how it affects brain-wide activity, they haven’t known entirely how the two are connected. A new study by a research team spanning four Boston-area institutions uses computational modeling of previously unappreciated physiological details to fill that gap and offer new insights into how ketamine works.
“This modeling work has helped decipher likely mechanisms through which ketamine produces altered arousal states as well as its therapeutic benefits for treating depression,” co-senior author Emery N. Brown, Edward Hood Taplin Professor of Computational Neuroscience and Medical Engineering at The Picower Institute for Learning and Memory at MIT, as well as an anesthesiologist at MGH and a Professor at Harvard Medical School.
The researchers from MIT, Boston University, Massachusetts General Hospital and Harvard University said the predictions of their model, published May 20 in Proceedings of the National Academy of Sciences, could help physicians make better use of the drug.
“When physicians understand what’s mechanistically happening when they administer a drug, they can possibly leverage that mechanism and manipulate it,” said study lead author Elie Adam, a Research Scientist at MIT who will soon join the Harvard Medical School faculty and launch a lab at MGH. “They gain a sense of how to enhance the good effects of the drug and how to mitigate the bad ones.”
Blocking the door
The core advance of the study involved biophysically modeling what happens when ketamine blocks the “NMDA” receptors in the brain’s cortex — the outer layer where key functions such as sensory processing and cognition take place. Blocking the NMDA receptors modulates the release of excitatory neurotransmitter glutamate.
When the neuronal channels (or doorways) regulated by the NMDA receptors open, they typically close slowly (like a doorway with a hydraulic closer that keeps it from slamming), allowing ions to go in and out of neurons, thereby regulating their electrical properties, Adam said. But, the channels of the receptor can be blocked by a molecule. Blocking by magnesium helps to naturally regulate ion flow. Ketamine, however, is an especially effective blocker.

Blocking slows the voltage build-up across the neuron’s membrane that eventually leads a neuron to “spike,” or send an electrochemical message to other neurons. The NMDA doorway becomes unblocked when the voltage gets high. This interdependence between voltage, spiking and blocking can equip NMDA receptors with faster activity than its slow closing speed might suggest. The team’s model goes further than ones before by representing how ketamine’s blocking and unblocking affect neural activity.
“Physiological details that are usually ignored can sometimes be central to understanding cognitive phenomena,” said co-corresponding author Nancy Kopell, a professor of math at BU. “The dynamics of NMDA receptors have more impact on network dynamics than has previously been appreciated.”
With their model, the scientists simulated how different doses of ketamine affecting NMDA receptors would alter the activity of a model brain network. The simulated network included key neuron types found in the cortex: one excitatory type and two inhibitory types. It distinguishes between “tonic” interneurons that tamp down network activity and “phasic” interneurons that react more to excitatory neurons.
The team’s simulations successfully recapitulated the real brain waves that have been measured via EEG electrodes on the scalp of a human volunteer who received various ketamine doses and the neural spiking that has been measured in similarly treated animals that had implanted electrode arrays. At low doses, ketamine increased brain wave power in the fast gamma frequency range (30-40 Hz). At the higher doses that cause unconsciousness, those gamma waves became periodically interrupted by “down” states where only very slow frequency delta waves occur. This repeated disruption of the higher frequency waves is what can disrupt communication across the cortex enough to disrupt consciousness.
But how? Key findings
Importantly, through simulations, they explained several key mechanisms in the network that would produce exactly these dynamics.

The first prediction is that ketamine can disinhibit network activity by shutting down certain inhibitory interneurons. The modeling shows that natural blocking and unblocking kinetics of NMDA-receptors can let in a small current when neurons are not spiking. Many neurons in the network that are at the right level of excitation would rely on this current to spontaneously spike. But when ketamine impairs the kinetics of the NMDA receptors, it quenches that current, leaving these neurons suppressed. In the model, while ketamine equally impairs all neurons, it is the tonic inhibitory neurons that get shut down because they happen to be at that level of excitation. This releases other neurons, excitatory or inhibitory from their inhibition allowing them to spike vigorously and leading to ketamine’s excited brain state. The network’s increased excitation can then enable quick unblocking (and reblocking) of the neurons’ NMDA receptors, causing bursts of spiking.
Another prediction is that these bursts become synchronized into the gamma frequency waves seen with ketamine. How? The team found that the phasic inhibitory interneurons become stimulated by lots of input of the neurotransmitter glutamate from the excitatory neurons and vigorously spike, or fire. When they do, they send an inhibitory signal of the neurotransmitter GABA to the excitatory neurons that squelches the excitatory firing, almost like a kindergarten teacher calming down a whole classroom of excited children. That stop signal, which reaches all the excitatory neurons simultaneously, only lasts so long, ends up synchronizing their activity, producing a coordinated gamma brain wave.
“The finding that an individual synaptic receptor (NMDA) can produce gamma oscillations and that these gamma oscillations can influence network-level gamma was unexpected,” said co-corresponding author Michelle McCarthy, a research assistant professor of math at BU. “This was found only by using a detailed physiological model of the NMDA receptor. This level of physiological detail revealed a gamma time scale not usually associated with an NMDA receptor.”
So what about the periodic down states that emerge at higher, unconsciousness-inducing ketamine doses? In the simulation, the gamma-frequency activity of the excitatory neurons can’t be sustained for too long by the impaired NMDA-receptor kinetics. The excitatory neurons essentially become exhausted under GABA inhibition from the phasic interneurons. That produces the down state. But then, after they have stopped sending glutamate to the phasic interneurons, those cells stop producing their inhibitory GABA signals. That enables the excitatory neurons to recover, starting a cycle anew.
Antidepressant connection?
The model makes another prediction that might help explain how ketamine exerts its antidepressant effects. It suggests that the increased gamma activity of ketamine could entrain gamma activity among neurons expressing a peptide called VIP. This peptide has been found to have health promoting effects, such as reducing inflammation, that last much longer than ketamine’s effects on NMDA receptors. The research team proposes that the entrainment of these neurons under ketamine could increase the release of the beneficial peptide, as observed when these cells are stimulated in experiments. This also hints at therapeutic features of ketamine that may go beyond anti-depressant effects. The research team acknowledges, however, that this connection is speculative and awaits specific experimental validation.
“The understanding that the sub cellular details of the NMDA receptor can lead to increased gamma oscillations was the basis for a new theory about how ketamine may work for treating depression,” Kopell said.
Additional co-authors of the study are Marek Kowalski, Oluwaseun Akeju, and Earl K. Miller.
The JPB Foundation, The Picower Institute for Learning and Memory, The Simons Center for The Social Brain, the National Institutes of Health, George J. Elbaum (MIT ’59, SM ’63, PhD ’67), Mimi Jensen, Diane B. Greene (MIT, SM ’78), Mendel Rosenblum, Bill Swanson, and annual donors to the Anesthesia Initiative Fund supported the research.

A discovery by Simona Stäger’s team could help come up with a treatment to the most serious form of leishmaniasis.
Leishmaniasis is a tropical disease affecting a growing number of people worldwide. Each year, between 700,000 and 1 million new cases are reported. Caused by a protozoan parasite of the genus Leishmania, which is transmitted to humans by the simple bite of a sand fly, leishmaniasis comprises three clinical forms, of which the visceral form is the most serious. If left untreated, visceral leishmaniasis, also known as black fever, is almost always fatal. Most cases occur in Bangladesh, Brazil, Ethiopia, India, Nepal, and Sudan.
Professor Simona Stäger of the Institut national de la recherche scientifique (INRS) and her team, in collaboration with other researchers from INRS and McGill University, have observed a surprising immune mechanism linked to chronic visceral leishmaniasis. This discovery could be an important step towards a new therapeutic approach to this disease. The results of their research have been published in the journal Cell Reports.
In many infections, CD4 T cells play a key role in defending the affected organism. Unfortunately, in the case of chronic infections such as leishmaniasis, maintaining the number of functional CD4 cells becomes an important issue, as the immune system is constantly activated to react against the pathogen affecting the infected person.
New immunity soldiers to the rescue
However, the study carried out by Professor Stäger in her laboratory at INRS’s Armand-Frappier Santé Biotechnologie Research Centre suggests that these cells may have more than one trick up their sleeve to maintain their vitality.
By observing these novel cells, the scientists noticed that they increase in number during the chronic phase of the disease and also that, like progenitor cells, they are capable of self-renewal or differentiation into other effector cells responsible for eliminating the parasite, or regulatory cells that inhibit the host’s response.

Professor Simona Stäger points out that CD4 T cells normally differentiate into effector cells from “naive” CD4 T cells. But during chronic infections, because of the constant need to generate effector cells, naive CD4 T cells are highly solicited and may become exhausted.
“We believe that in the chronic phase of visceral leishmaniasis, the new population we have identified is responsible for generating effector and regulatory cells. This would allow the host to prevent exhaustion of its existing pool of naive CD4 Tcells for a certain antigen,” explains Ph.D. student and first author of the study, Sharada Swaminathan.
The new lymphocyte population discovered by the INRS team could be a decisive immune booster, taking over from over-solicited naive CD4 T cells.
“If we can figure out how to direct this new lymphocyte population to differentiate into a protective effector cell, it could help the host get rid of the Leishmania parasite.”
—  Simona Stäger, Vice-Director of the Infectiopole and member of Pasteur Network
A cure for other infections?
The study also mentions that cells similar to this new CD4 T lymphocyte population have been observed in mice infected with lymphocytic choriomeningitis virus and in mice carrying the H. polygyrus intestinal worm. So it is quite possible that this population is present in other chronic infections or in other chronic inflammatory environments.
This overlap sets the stage for an even wider scope for the discovery made by Professor Stäger’s team. “If our hypothesis is correct, these cells could be exploited therapeutically not only for visceral leishmaniasis, but also for other chronic infections,” concludes the researcher.

Researchers from the University of Liverpool and Queen Mary University of London have published the first study in the UK to demonstrate the benefits of lung cancer screening across socioeconomic groups. Evidence in the new study illustrates the value and importance of screening, especially for those who live in areas of economic deprivation[1].
Lung cancer affects the lives of about 40,000 people a year in the UK and previous studies from Liverpool researchers illustrate the unequivocal benefit of lung cancer screening in identified high risk groups.
In a newly published Lancet Regional Health Europe paper, lung cancer researchers further demonstrate the benefits of low-dose CT lung cancer screening. The latest study illustrates lung cancer outcomes are comparable across all socioeconomic groups.
Significantly, it also demonstrates that screening may provide additional health benefits for other smoking-related diseases. The analysis showed that conditions COPD and emphysema, both of which disproportionately affect lower socioeconomic groups, were less often the cause of death when subjects received a low-dose CT scan.
Researchers examined long-term outcomes of recruited participants from across the socioeconomic spectrum. This allowed assessment of the impact of socioeconomic status on a variety of aspects, including initial recruitment, selection for screening, lung cancer detection, and long-term mortality benefit from lung cancer and other diseases. It is shown that those from a lower socioeconomic group benefited from low-dose-CT screening in terms of lung cancer survival to the same extent as those from more affluent groups. However, they were more likely to benefit in terms of death from COPD and emphysema.
Professor John Field, Professor of Molecular Oncology, University of Liverpool and lead author on the paper said: “The impact of low-dose CT lung cancer screening has been previously demonstrated in a number of international clinical trials, including the UKLS study here in the UK. However, this is the first time that the long-term impact of risk-stratified lung cancer screening has been compared across different socioeconomic groups, demonstrating that those disadvantaged groups at the greatest risk of developing the disease benefit as much as those in less deprived areas.”
Dr Chris Warburton, Respiratory Consultant at Liverpool University Hospitals NHS Foundation Trust and Clinical Lead for the Targeted Lung Health Check Programme for the NHS Cheshire and Merseyside Cancer Alliance said: “This is excellent data which demonstrates that lung cancer screening of high risk populations not only delivers benefits in lung cancer outcomes for the most deprived in our society, but it could also have wider beneficial effects on other smoking related diseases such as COPD and cardiovascular disease. The Cancer Alliance would encourage anyone offered a Lung Health Check to attend this important appointment which might just help to prolong their life.”
Professor John Field worked with Dr Michael Davies, from the University of Liverpool’s Institute of Systems, Molecular & Integrative Biology, and Daniel Vulkan, Professor Rhian Gabe, and Professor Stephen Duffy, from the Wolfson Institute of Preventive Medicine, Queen Mary University of London.

Professor Stephen Duffy said: “These results indicate the potential for lung cancer screening to address some serious inequalities in health. As the targeted programme is rolled out nationally, we need to make an effort to deliver the service to those deprived populations who need it most.”
The UKLS study was funded by the Health Technology Assessment programme of the National Institute for Health Research (NIHR). Dr Michael Davies is a Roy Castle Lung Cancer Foundation Senior Research Fellow. Daniel Vulkan’s and Professor Stephen Duffy’s contributions to this research were funded by the NIHR Policy Research Programme.
[1] Deprivation, or lower socioeconomic status, as measured in the UK by the Index of Multiple Deprivation (IMD)

Generative artificial intelligence (AI), such as GPT-4, can help predict whether an emergency room patient needs to be admitted to the hospital even with only minimal training on a limited number of records, according to investigators at the Icahn School of Medicine at Mount Sinai. Details of the research were published in the May 21 online issue of the Journal of the American Medical Informatics Association.
In the retrospective study, the researchers analyzed records from seven Mount Sinai Health System hospitals, using both structured data, such as vital signs, and unstructured data, such as nurse triage notes, from more than 864,000 emergency room visits while excluding identifiable patient data. Of these visits, 159,857 (18.5 percent) led to the patient being admitted to the hospital.
The researchers compared GPT-4 against traditional machine-learning models such as Bio-Clinical-BERT for text and XGBoost for structured data in various scenarios, assessing its performance to predict hospital admissions independently and in combination with the traditional methods.
“We were motivated by the need to test whether generative AI, specifically large language models (LLMs) like GPT-4, could improve our ability to predict admissions in high-volume settings such as the Emergency Department,” says co-senior author Eyal Klang, MD, Director of the Generative AI Research Program in the Division of Data-Driven and Digital Medicine (D3M) at Icahn Mount Sinai. “Our goal is to enhance clinical decision-making through this technology. We were surprised by how well GPT-4 adapted to the ER setting and provided reasoning for its decisions. This capability of explaining its rationale sets it apart from traditional models and opens up new avenues for AI in medical decision-making.”
While traditional machine-learning models use millions of records for training, LLMs can effectively learn from just a few examples. Moreover, according to the researchers, LLMs can incorporate traditional machine-learning predictions, improving performance
“Our research suggests that AI could soon support doctors in emergency rooms by making quick, informed decisions about patient admissions. This work opens the door for further innovation in health care AI, encouraging the development of models that can reason and learn from limited data, like human experts do,” says co-senior author Girish N. Nadkarni, MD, MPH, Irene and Dr. Arthur M. Fishberg Professor of Medicine at Icahn Mount Sinai, Director of The Charles Bronfman Institute of Personalized Medicine, and System Chief of D3M. “However, while the results are encouraging, the technology is still in a supportive role, enhancing the decision-making process by providing additional insights, not taking over the human component of health care, which remains critical.”
The research team is investigating how to apply large language models to health care systems, with the goal of harmoniously integrating them with traditional machine-learning methods to address complex challenges and decision-making in real-time clinical settings.

“Our study informs how LLMs can be integrated into health care operations. The ability to rapidly train LLMs highlights their potential to provide valuable insights even in complex environments like health care,” says Brendan Carr, MD, MA, MS, a study co-author and emergency room physician who is Chief Executive Officer of Mount Sinai Health System. “Our study sets the stage for further research on AI integration in health care across the many domains of diagnostic, treatment, operational, and administrative tasks that require continuous optimization.”
The paper is titled “Evaluating the accuracy of a state-of-the-art large language model for prediction of admissions from the emergency room.”
The remaining authors of the paper, all with Icahn Mount Sinai, are Benjamin S. Glicksberg, PhD; Dhaval Patel, BS; Ashwin Sawant, MD; Akhil Vaid, MD; Ganesh Raut, BS; Alexander W. Charney, MD, PhD; Donald Apakama, MD; and Robert Freeman, RN.
The work was supported by the National Heart Lung and Blood Institute NIH grant 5R01HL141841-05.

Periodontitis is an inflammatory gum disease driven by bacterial infection and left untreated it can lead to complications including tooth loss. The disease also been associated with diabetes mellitus, preterm birth, cardiovascular disease, rheumatoid arthritis and cancer. One of the chief bacterial culprits behind periodontitis is Porphyromonas gingivalis, which colonizes biofilms on tooth surfaces and proliferates in deep periodontal pockets.
Matcha, a finely ground green tea powder, may help keep P. gingivalis at bay. This week in Microbiology Spectrum, an open-access ASM journal, researchers in Japan report that matcha inhibited the growth of P. gingivalis in lab experiments. In addition, in a clinical study involving 45 people with periodontitis, people who used matcha mouthwash showed significantly lower levels of P. gingivalis in saliva samples than at the start of the study. “Matcha may have clinical applicability for prevention and treatment of periodontitis,” the authors noted in the paper.
Camellia sinensis is a green tea plant that has long been studied for its potential antimicrobial effects against bacteria, fungi and viruses. A previous study on mice found that green tea extract can inhibit the growth of pathogens, including Escherichia coli. Other research has found that the extract can inhibit the growth of P. gingivalis and reduce its adherence to oral epithelial cells. In addition, observational studies have associated green tea consumption with better health.
Matcha, which is used in traditional ceremonies and for flavoring in beverages and sweets, is made from raw leaves of C. sinensis. For the new study, researchers from the Nihon University School of Dentistry at Matsudo, the National Institute of Infectious Disease in Tokyo and other institutions carried out a series of in vitro experiments to test the efficacy of a matcha solution against 16 oral bacterial species, including 3 strains of P. gingivalis. The matcha mouthwash showed little activity against strains of commensal oral bacteria.
Within 2 hours, nearly all the cultured P. gingivalis cells had been killed by the matcha extract, and after 4 hours of exposure, all the cells were dead. Those findings suggested a bactericidal activity against the pathogen.
The researchers then recruited 45 people diagnosed with chronic periodontitis at the Nihon University Hospital School of Dentistry at Matsudo for a follow up clinical study. The patients were randomly assigned to 3 groups: One group received barley tea mouthwash, the second received the mouthwash made from matcha extract, and the third received mouthwash that included sodium azulene sulfonate hydrate, which is used to treat inflammation. Saliva samples were collected before and after the intervention and analyzed using PCR, and participants were instructed to rinse twice daily.
The analysis revealed that patients in the group that used matcha mouthwash showed a significant reduction in the level of P. gingivalis. Patients in the other 2 groups did not show that same significant reduction.
While the new study isn’t the first to probe the antimicrobial effects of tea-derived compounds on P. Gingivalis, the researchers note that it does support the potential benefits of matcha as part of a treatment plan for people with periodontal disease.

New mathematical tools revealing how quickly cell proteins break down are poised to uncover deeper insights into how we age, according to a recently published paper co-authored by a Mississippi State researcher and his colleagues from Harvard Medical School and the University of Cambridge.
Galen Collins, assistant professor in MSU’s Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, co-authored the groundbreaking paper published in the Proceedings of the National Academy of Sciences, or PNAS, in April.
“We already understand how quickly proteins are made, which can happen in a matter of minutes,” said Collins, who is also a scientist in the Mississippi Agricultural and Forestry Experiment Station. “Until now, we’ve had a very poor understanding of how much time it takes them to break down.”
The paper in applied mathematics, “Maximum entropy determination of mammalian proteome dynamics,” presents the new tools that quantify the degradation rates of cell proteins — how quickly they break down — helping us understand how cells grow and die and how we age. Proteins — complex molecules made from various combinations of amino acids — carry the bulk of the workload within a cell, providing its structure, responding to messages from outside the cell and removing waste.
The results proved that not all proteins degrade at the same pace but instead fall into one of three categories, breaking down over the course of minutes, hours or days. While previous research has examined cell protein breakdown, this study was the first to quantify mathematically the degradation rates of all cell protein molecules, using a technique called maximum entropy.
“For certain kinds of scientific questions, experiments can often reveal infinitely many possible answers; however, they are not all equally plausible,” said lead author Alexander Dear, research fellow in applied mathematics at Harvard University. “The principle of maximum entropy is a mathematical law that shows us how to precisely calculate the plausibility of each answer — its ‘entropy’ — so that we can choose the one that is the most likely.”
“This kind of math is sort of like a camera that zooms in on your license plate from far away and figures out what the numbers should be,” Collins said. “Maximum entropy gives us a clear and precise picture of how protein degradation occurs in cells.”
In addition, the team used these tools to study some specific implications of protein degradation for humans and animals. For one, they examined how those rates change as muscles develop and adapt to starvation.

“We found that starvation had the greatest impact on the intermediate group of proteins in muscular cells, which have a half-life of a few hours, causing the breakdown to shift and accelerate,” Collins said. “This discovery could have implications for cancer patients who experience cachexia, or muscle wasting due to the disease and its treatments.”
They also explored how a shift in the breakdown of certain cell proteins contributes to neurodegenerative disease.
“These diseases occur when waste proteins, which usually break down quickly, live longer than they should,” Collins said. “The brain becomes like a teenager’s bedroom, accumulating trash, and when you don’t clean it up, it becomes uninhabitable.”
Dear affirmed the study’s value lies not only in what it revealed about cell protein degeneration, but also in giving scientists a new method to investigate cell activity with precision.
“Our work provides a powerful new experimental method for quantifying protein metabolism in cells,” he said. “Its simplicity and rapidity make it particularly well-suited for studying metabolic changes.”
Collins’s post-doctoral advisor at Harvard and a co-author of the article, the late Alfred Goldberg, was a pioneer in studying the life and death of proteins. Collins noted this study was built on nearly five decades of Goldberg’s research and his late-career collaboration with mathematicians from the University of Cambridge. After coming to MSU a year ago, Collins continued collaborating with his colleagues to complete the paper.
“It’s an incredible honor to be published in PNAS, but it was also a lot of fun being part of this team,” Collins said. “And it’s very meaningful to see my former mentor’s body of work wrapped up and published.”

Natural materials like bone, bird feathers and wood have an intelligent approach to physical stress distribution, despite their irregular architectures. However, the relationship between stress modulation and their structures has remained elusive. A new study that integrates machine learning, optimization, 3D printing and stress experiments allowed engineers to gain insight into these natural wonders by developing a material that replicates the functionalities of human bone for orthopedic femur restoration.
Fractures of the femur, the long bone in the upper leg, are a widespread injury in humans and are prevalent among elderly individuals. The broken edges cause stress to concentrate at the crack tip, increasing the chances that the fracture will lengthen. Conventional methods of repairing a fractured femur typically involve surgical procedures to attach a metal plate around the fracture with screws, which may cause loosening, chronic pain and further injury.
The study, led by University of Illinois Urbana-Champaign civil and environmental engineering professor Shelly Zhang and graduate student Yingqi Jia in collaboration with professor Ke Liu from Peking University, introduces a new approach to orthopedic repair that uses a fully controllable computational framework to produce a material that mimics bone.
The study findings are published in the journal Nature Communications.
“We started with materials database and used a virtual growth stimulator and machine learning algorithms to generate a virtual material, then learn the relationship between its structure and physical properties,” Zhang said. “What separates this work from past studies is that we took things a step further by developing a computational optimization algorithm to maximize both the architecture and stress distribution we can control.”
In the lab, Zhang’s team used 3D printing to fabricate a full-scale resin prototype of the new bio-inspired material and attached it to a synthetic model of a fractured human femur.
“Having a tangible model allowed us to run real-world measurements, test its efficacy and confirm that it is possible to grow a synthetic material in a way analogous to how biological systems are built,” Zhang said. “We envision this work helping to build materials that will stimulate bone repair by providing optimized support and protection from external forces.”
Zhang said this technique can be applied to various biological implants wherever stress manipulation is needed. “The method itself is quite general and can be applied to different types of materials such like metals, polymers — virtually any type of material,” she said. “The key is the geometry, local architecture and the corresponding mechanical properties, making applications almost endless.”
The David C. Crawford Faculty Scholar Award from the U. of I. supported this research.
Zhang also is affiliated with mechanical science and engineering and the National Center for Supercomputing Applications at Illinois.