Researchers at the National Institutes of Health applied artificial intelligence (AI) to a technique that produces high-resolution images of cells in the eye. They report that with AI, imaging is 100 times faster and improves image contrast 3.5-fold. The advance, they say, will provide researchers with a better tool to evaluate age-related macular degeneration (AMD) and other retinal diseases.
“Artificial intelligence helps overcome a key limitation of imaging cells in the retina, which is time,” said Johnny Tam, Ph.D., who leads the Clinical and Translational Imaging Section at NIH’s National Eye Institute.
Tam is developing a technology called adaptive optics (AO) to improve imaging devices based on optical coherence tomography (OCT). Like ultrasound, OCT is noninvasive, quick, painless, and standard equipment in most eye clinics.
Imaging RPE cells with AO-OCT comes with new challenges, including a phenomenon called speckle. Speckle interferes with AO-OCT the way clouds interfere with aerial photography. At any given moment, parts of the image may be obscured. Managing speckle is somewhat similar to managing cloud cover. Researchers repeatedly image cells over a long period of time. As time passes, the speckle shifts, which allows different parts of the cells to become visible. The scientists then undertake the laborious and time-consuming task of piecing together many images to create an image of the RPE cells that’s speckle-free.
Tam and his team developed a novel AI-based method called parallel discriminator generative adverbial network (P-GAN) — a deep learning algorithm. By feeding the P-GAN network nearly 6,000 manually analyzed AO-OCT-acquired images of human RPE, each paired with its corresponding speckled original, the team trained the network to identify and recover speckle-obscured cellular features.
When tested on new images, P-GAN successfully de-speckled the RPE images, recovering cellular details. With one image capture, it generated results comparable to the manual method, which required the acquisition and averaging of 120 images. With a variety of objective performance metrics that assess things like cell shape and structure, P-GAN outperformed other AI techniques. Vineeta Das, Ph.D., a postdoctoral fellow in the Clinical and Translational Imaging Section at NEI, estimates that P-GAN reduced imaging acquisition and processing time by about 100-fold. P-GAN also yielded greater contrast, about 3.5 greater than before.
“Adaptive optics takes OCT-based imaging to the next level,” said Tam. “It’s like moving from a balcony seat to a front row seat to image the retina. With AO, we can reveal 3D retinal structures at cellular-scale resolution, enabling us to zoom in on very early signs of disease.”
While adding AO to OCT provides a much better view of cells, processing AO-OCT images after they’ve been captured takes much longer than OCT without AO.

Tam’s latest work targets the retinal pigment epithelium (RPE), a layer of tissue behind the light-sensing retina that supports the metabolically active retinal neurons, including the photoreceptors. The retina lines the back of the eye and captures, processes, and converts the light that enters the front of the eye into signals that it then transmits through the optic nerve to the brain. Scientists are interested in the RPE because many diseases of the retina occur when the RPE breaks down.
By integrating AI with AO-OCT, Tam believes that a major obstacle for routine clinical imaging using AO-OCT has been overcome, especially for diseases that affect the RPE, which has traditionally been difficult to image.
“Our results suggest that AI can fundamentally change how images are captured,” said Tam. “Our P-GAN artificial intelligence will make AO imaging more accessible for routine clinical applications and for studies aimed at understanding the structure, function, and pathophysiology of blinding retinal diseases. Thinking about AI as a part of the overall imaging system, as opposed to a tool that is only applied after images have been captured, is a paradigm shift for the field of AI.”

A team of researchers at Nagoya University in Japan has discovered that aldehydes are metabolic byproducts associated with premature aging. Published in Nature Cell Biology, their findings reveal insights into premature aging diseases and potential strategies to combat aging in healthy individuals such as controlling exposure to aldehyde-inducing substances including alcohol, pollution, and smoke.
A person’s health can be harmed by aldehydes. However, the group’s findings suggest these detrimental effects also include aging. The team who made this discovery included Yasuyoshi Oka, Yuka Nakazawa, Mayuko Shimada, and Tomoo Ogi of Nagoya University.
“DNA damage is linked with aging phenotypes,” said Oka. “However, for the first time, we propose a relationship between aldehyde-derived DNA damage and premature aging.”
The researchers hypothesized that there might be a link between aldehydes and aging since individuals with premature aging disorders, like AMeD syndrome, exhibit inadequate activity of enzymes, like ALDH2, that break down aldehydes.
For healthy individuals, ALDH2 is also important in our response to alcohol. When a person drinks wine or beer, the liver metabolizes the alcohol into aldehydes so it can be eliminated from the body. The activity of ALDH2 is important for converting the aldehydes into a non-toxic substance.
Aldehydes are harmful because they are highly reactive with DNA and proteins. In the body, they form DNA-protein crosslinks (DPCs) that block important enzymes in typical cell proliferation and maintenance processes, causing these processes to malfunction and the patient to age.
Focusing on DPCs caused by aldehyde, the scientists used a method called DPC-seq to investigate the link between aldehyde accumulation and DNA damage in premature-aging disease patients. In a series of experiments, the researchers discovered that the TCR complex, VCP/p97, and the proteasome are involved in the removal of formaldehyde-induced DPCs in actively transcribed regions. This was confirmed by a mouse model lacking both aldehyde clearance processes and the TCR pathway that showed worse AMeD syndrome symptoms.

These processes are important because they are related to the clearance of aldehydes. It suggests an association between premature aging diseases and aldehyde accumulation.
Professor Ogi is hopeful about the implications of their findings, stating: “By elucidating the mechanism by which DNA damage heals quickly, we have revealed part of the cause of genetic premature aging.”
“Our research opens up new avenues for understanding the underlying mechanisms of premature aging diseases and offers potential targets for therapeutic intervention,” Oka said. “By elucidating the role of aldehydes in DNA damage and aging, we are paving the way for future studies aimed at developing novel treatments and interventions.”
He continued: “The development of therapeutic drugs has not progressed because we have not fully understood the causes of AMeD syndrome and Cockayne syndrome. This study suggests that the patient’s pathological condition is related to DPC derived from aldehydes generated within cells. These results are expected to help in the search for compounds that remove aldehydes, thus aiding in the formulation of therapeutic drug candidates.”
This research has implications that extend beyond genetic diseases, as their findings suggest that aldehyde-induced DNA damage may play a role in the aging process in healthy individuals too. By pinpointing aldehydes as substances that contribute to aging, this study sheds light on the intricate connection between environmental factors and cellular aging. This may have significant implications for human health and lifespan.

The Wistar Institute’s associate professor Mohamed Abdel-Mohsen, Ph.D., along with his team and collaborators, has identified sugar abnormalities in the blood that may promote biological aging and inflammation in people living with HIV (PLWH). The findings, taken from a large data study comprising more than 1200 participants, are detailed in the new paper, “Immunoglobulin G N-glycan Markers of Accelerated Biological Aging During Chronic HIV Infection,” published in the journal Nature Communications.
Despite advances in HIV treatment, notably the success of antiretroviral therapy (ART) in suppressing the virus to undetectable levels, HIV remains incurable, with the virus persisting in a dormant state within the body. This chronic presence is linked to long-term health issues, including persistent inflammation and a higher prevalence of aging-related diseases such as cancer and neurocognitive disorders. These conditions tend to occur more frequently and at an earlier age in PLWH compared to the general population.
Abdel-Mohsen seeks to understand how chronic viral infection causes this accelerated biological aging, which refers to the body aging faster than one’s chronological years would typically indicate. By understanding the molecular mechanisms behind accelerated biological aging in people living with chronic viral infections, scientists can begin to formulate strategies to mitigate the negative effects.
While many factors in the body can contribute to accelerated biological aging, researchers focused on a novel factor: abnormalities of the human glycome — the totality of the various sugar structures circulating throughout the body. Previous studies have established a connection between aging and shifts in the glycan composition of immunoglobulins (IgGs), which are critical for immune regulation. As people age, their IgGs lose anti-inflammatory properties and gain pro-inflammatory characteristics.
Abdel-Mohsen’s research investigates whether living with a chronic viral infection, such as HIV infection, exacerbates these changes, leading to premature aging and related diseases.
By comparing glycan profiles in more than 1200 individuals, both with and without HIV, the team discovered that PLWH exhibit elevated levels of inflammatory and pro-aging IgG glycan signatures. In a remarkable step forward, the team developed a machine-learning model that uses these glycan signatures to estimate the biological age of PLWH and assess the rate of aging acceleration. This glycan signature also has the potential to predict the onset of comorbid conditions in PLWH, such as cancer, years in advance.
To confirm that these glycan-associated disruptions were causal rather than merely correlative, the research team engineered HIV-specific antibodies designed to exhibit the same kind of aberrant IgG glycan modifications observed in PLWH. Testing these glycoengineered antibodies in vitro confirmed that the modified antibodies were less effective at mounting an immune response than their unmodified counterparts, suggesting that these sugar abnormalities might directly contribute to the worse clinical outcomes observed. Importantly, when they designed these antibodies to have glycans similar to those found in biologically younger individuals, these antibodies demonstrated a remarkable ability to enhance the immune system’s ability to fight virus-infected cells.
“Utilizing glycan signatures to predict early onset of diseases in people living with HIV marks a pivotal shift towards proactive healthcare,” said Abdel-Mohsen. “This could significantly alter clinical outcomes, allowing for timely interventions and personalized treatment plans. The impact on treatment and management in the HIV community could be revolutionary. Beyond biomarkers, antibodies glycoengineered to mimic biologically younger glycans offer a new therapeutic avenue. This method could enhance immune responses, paving the way for innovative treatments.”

Study reveals diminished quality of life among patients with chronic limb-threatening ischemia, a severe form of peripheral artery disease, and emphasizes the benefits of revascularization on wellbeing
Over 200 million people around the world experience peripheral artery disease (PAD) — a condition caused by the narrowing of the blood vessels from the heart to the lower limbs that leads to pain when walking — and for roughly 1-in-10 this advances to chronic limb-threatening ischemia (CLTI), an advanced form of PAD. Those with CLTI often suffer severe pain even at rest, caused by fatty plaque buildup obstructing blood flow, typically to the leg or foot. Those with CLTI face elevated risks of amputation, cardiovascular disease and premature death, yet research on the condition’s impact on quality of life remains limited.
Investigators from both of Mass General Brigham’s founding members, Brigham and Women’s Hospital (BWH) and Massachusetts General Hospital (MGH), as well as Boston Medical Center (BMC), sought to address this problem. Following their previous study highlighting the clinical results of the BEST-CLI trial — Best Endovascular versus Best Surgical Therapy for Patients with Critical Limb Ischemia — published in the New England Journal of Medicine (NEJM), the team assessed patient health-related quality of life before and after revascularization treatment. Results are published in Circulation.
“Our study indicates that patients with CLTI have a notably poor quality of life — substantially lower than with many other chronic conditions,” said Matthew Menard, MD, co-director of the Endovascular Surgery Program at BWH and co-principal investigator of BEST-CLI. “Our findings show that revascularization, which restores sufficient blood flow back into the legs, significantly improves quality of life. This confirms the critical role that revascularization plays not just in extending the length of patients’ lives but also its importance in optimizing their wellbeing.”
Among patients with CLTI, those eligible for surgical treatment often have two options: surgical bypass (Bypass), where surgeons restore blood and oxygen to the lower limb by reconstructing the blocked vessel, or endovascular therapy (Endo), which involves placing a stent or catheter inside an artery and opening it up to bring blood flow through a blockage.
Funded by the National Heart, Lung, and Blood Institute, with ongoing post-enrollment support from theNovo Nordisk Foundation, the BEST-CLI trial enrolled over 1,800 patients with CLTI from 150 research sites in the U.S., Canada, Finland, Italy, and New Zealand between August of 2014 and October of 2019. Investigators assessed how clinical outcomes (previously reported in NEJM) and quality of life metrics varied between revascularization techniques.
“Medicine is generally moving towards a more patient-centric model of care. That means looking at what’s best for each patient, taking into account an evidence-based approach. Quality of life is one important element in this determination,” said co-principal investigator Kenneth Rosenfield, MD, head of the Section of Vascular Medicine and Intervention in the Division of Cardiology at MGH.

Investigators sorted 1,528 participants into two cohorts. The first cohort was made up of 1,193 patients, all of whom had an available, good-quality, single-segment great saphenous vein (SSGSV), which previous studies have shown is optimal for Bypass. The second cohort was made up of 335 patients who did not have an available SSGSV. Patients in both cohorts were randomized to undergo Bypass or Endo procedures. Researchers assessed quality of life by administering voluntary surveys asking participants about pain levels, activities of daily living, disease symptoms and severity, physical activity, and mental health (anxiety and depression). Surveys were collected at baseline, 30 days post-procedure, at three months, 12 months, then once yearly until the end of the study.
“Patient-reported outcome measures are essential to our understanding of the patient experience,” said co-principal investigator Alik Farber, MD, MBA, interim chair of the Department of Surgery, chief of the Division of Vascular and Endovascular Surgery at BMC and professor of Surgery and Radiology at Boston University Chobanian & Avedisian School of Medicine. “Yet these metrics are not often used and sometimes ignored. Here we found an opportunity to hear our patients’ voices and use them to improve CLTI outcomes.”
While the trial’s previously published clinical outcomes revealed that patients treated with Bypass had fewer major amputations and less need for repeat procedures than those treated with Endo, quality of life did not significantly differ between treatments. Survey results instead revealed that participants generally experienced significant improvements in quality of life after treatment, regardless of their cohort or whether they underwent Bypass or Endo. They further highlighted that patients with CLTI overwhelmingly conveyed that their quality of life was low upon entering the trial, before receiving treatment.
This study is limited in that patients filled out quality-of-life questionnaires at distinct periods throughout the trial, but these time points did not necessarily line up with significant health events such as additional revascularization procedures or amputations. Further, there remains a dearth of quality-of-life research for patients with PAD, and there are no specific metrics to assess the quality of life for patients with PAD or CLTI.
Going forward, the team aims to assess differences in the cost-effectiveness of these procedures, and how cost, among other factors, affects patient quality of life and overall health outcomes.
“The next step is to integrate quality-of-life measures into a more sophisticated care plan to account for the clinical status of the patient and the cost-effectiveness of treatment options, both for the patient and the viability of the healthcare system,” said Farber.

A large randomized trial conducted at Tampere University and the University of Helsinki shows that a new three-step prostate cancer screening method can find a considerable number of aggressive cancers. Population-level screening programmes have not been launched in most countries including Finland.
The ProScreen trial coordinated by Tampere University and the University of Helsinki investigated the performance of a three-step prostate cancer screening method. The aim was to analyse whether the new method would efficiently reduce mortality while decreasing the major adverse effect of previous screening methods: the overdiagnosing of insignificant prostate cancers.
Some prostate cancers are clinically insignificant because they do not become symptomatic even when left untreated. Such cancers are frequently detected at autopsy. Thus, treating cancer with a good prognosis does not bring benefits, but the treatment itself can still harm the patients’ quality of life.
The screening method used in the ProScreen study includes two blood tests and, if necessary, magnetic resonance imaging (MRI) of the prostate. The previously studied screening method has only been based on one blood test, the prostate-specific antigen test (PSA).
In the ProScreen study, both blood tests were positive in 7% of the participants and they were invited to an MRI of the prostate. In about half of these men, a suspicious area was detected by MRI and a prostate biopsy was taken.
Cancer was eventually found in about 2% of the participants. Clinically insignificant cancers were diagnosed in four in a thousand men.
“We have previously demonstrated that PSA screening can decrease prostate cancer mortality to some extent. However, PSA screening produces so many unnecessary cancer diagnoses that the harms outweigh the benefits. The new results show that the three-step method now used produces fewer insignificant cancer diagnoses than PSA screening,” says Professor of Epidemiology Anssi Auvinen from Tampere University.

Diagnosing cancer with a good prognosis is not beneficial
Some prostate cancers are clinically insignificant, i.e. they will not progress to the symptomatic stage or cause any harm. The co-lead investigator of the project, Professor of Urology Antti Rannikko from the University of Helsinki, points out that the detection of such latent cancers does not bring any benefits and that they should not even be diagnosed.
“The vast majority of tumours found with the previous PSA screenings are low-risk cases that are likely to represent overdiagnosis. Most of them do not progress to the symptomatic stage even when left untreated. If a prostate cancer with a good prognosis is diagnosed, the primary treatment is always active surveillance,” Rannikko says.
Local prostate cancer is usually treated surgically or with radiation therapy. The common side effects of treatment include erectile dysfunction, urinary incontinence, and bowel symptoms.
The main goal of screening is to reduce cancer mortality
The study included more than 60,000 men aged 50 — 63 years who were randomly allocated for either the three-step screening or a control group without intervention.

The study continues and the study population will expand to also include the neighbouring municipalities of Tampere and Helsinki. Men who have already participated will be invited to a new screening after 2 — 6 years based on the outcomes of their first screening.
No population-level screening programme has been launched in Finland or in most other European countries but there is a health policy debate on the topic.
According to the researchers, only preliminary evidence of the benefits of the new screening model is available so far. However, the results seem to indicate that major benefits could potentially be achieved in the future. The benefits can only be estimated after a 10-year follow up when the effects on prostate cancer mortality have been analysed.
“The aim of cancer screening is always to reduce mortality. The main criterion for decisions on cancer screening should always be the reduction of mortality to be gained,” Auvinen says.
“The ProScreen study, due to its large size and randomised design, can produce the research evidence needed to justify screening decisions,” he adds. There is currently no reliable research data on the benefits and harms of MRI screening.
The study was carried out by a large team of researchers, including radiologists, pathologists, urologists, and experts from other fields at Tampere University and Tampere University Hospital (TAYS), as well as the University of Helsinki and Helsinki University Hospital (HUS). The cooperation partners included the local laboratory networks and Lund University.
The study was supported by Cancer Foundation Finland, Research Council of Finland, Jane and Aatos Erkko Foundation, Päivikki and Sakari Sohlberg Foundation and state research funding administered by the Pirkanmaa wellbeing county.
The research article was published in the JAMA — Journal of the American Medical Association.
Prostate cancer is the most common cancer in men.

A new review of research evidence has explored the key differences in how women and men sleep, variations in their body clocks, and how this affects their metabolism.
Published in Sleep Medicine Reviews, the paper highlights the crucial role sex plays in understanding these factors and suggests a person’s biological sex should be considered when treating sleep, circadian rhythm and metabolic disorders.
Differences in sleep
The review found women rate their sleep quality lower than men’s and report more fluctuations in their quality of sleep, corresponding to changes throughout the menstrual cycle.
“Lower sleep quality is associated with anxiety and depressive disorders, which are twice as common in women as in men,” says Dr Sarah L. Chellappa from the University of Southampton and senior author of the paper. “Women are also more likely than men to be diagnosed with insomnia, although the reasons are not entirely clear. Recognising and comprehending sex differences in sleep and circadian rhythms is essential for tailoring approaches and treatment strategies for sleep disorders and associated mental health conditions.”
The paper’s authors also found women have a 25 to 50 per cent higher likelihood of developing restless legs syndrome and are up to four times as likely to develop sleep-related eating disorder, where people eat repeatedly during the night.
Meanwhile, men are three times more likely to be diagnosed with obstructive sleep apnoea (OSA). OSA manifests differently in women and men, which might explain this disparity. OSA is associated with a heightened risk of heart failure in women, but not men.

Sleep lab studies found women sleep more than men, spending around 8 minutes longer in non-REM (Rapid Eye Movement) sleep, where brain activity slows down. While the time we spend in NREM declines with age, this decline is more substantial in older men. Women also entered REM sleep, characterised by high levels of brain activity and vivid dreaming, earlier than men.
Variations in body clocks
The team of all women researchers from the University of Southampton in the UK, and Stanford University and Harvard University in the United States, found differences between the sexes are also present in our circadian rhythms.
They found melatonin, a hormone that helps with the timing of circadian rhythms and sleep, is secreted earlier in women than men. Core body temperature, which is at its highest before sleep and its lowest a few hours before waking, follows a similar pattern, reaching its peak earlier in women than in men.
Corresponding to these findings, other studies suggest women’s intrinsic circadian periods are shorter than men’s by around six minutes.
Dr Renske Lok from Stanford University, who led the review, says: “While this difference may be small, it is significant. The misalignment between the central body clock and the sleep/wake cycle is approximately five times larger in women than in men. Imagine if someone’s watch was consistently running six minutes faster or slower. Over the course of days, weeks, and months, this difference can lead to a noticeable misalignment between the internal clock and external cues, such as light and darkness.

“Disruptions in circadian rhythms have been linked to various health problems, including sleep disorders, mood disorders and impaired cognitive function. Even minor differences in circadian periods can have significant implications for overall health and well-being.”
Men tend to be later chronotypes, preferring to go to bed and wake up later than women. This may lead to social jet lag, where their circadian rhythm doesn’t align with social demands, like work. They also have less consistent rest-activity schedules than women on a day-to-day basis.
Impact on metabolism
The research team also investigated if the global increase in obesity might be partially related to people not getting enough sleep — with 30 per cent of 30- to 64-year-olds sleeping less than six hours a night in the United States, with similar numbers in Europe.
There were big differences between how women’s and men’s brains responded to pictures of food after sleep deprivation. Brain networks associated with cognitive (decision making) and affective (emotional) processes were twice as active in women than in men. Another study found women had a 1.5 times higher activation in the limbic region (involved in emotion processing, memory formation, and behavioural regulation) in response to images of sweet food compared to men.
Despite this difference in brain activity, men tend to overeat more than women in response to sleep loss. Another study found more fragmented sleep, taking longer to get to sleep, and spending more time in bed trying to get to sleep were only associated with more hunger in men.
Both women and men nightshift workers are more likely to develop type 2 diabetes, but this risk is higher in men. Sixty-six per cent of women nightshift workers experienced emotional eating and another study suggests they are around 1.5 times more likely to be overweight or obese compared to women working day shifts.
The researchers also found emerging evidence on how women and men respond differently to treatments for sleep and circadian disorders. For example, weight loss was more successful in treating women with OSA than men, while women prescribed zolpidem (an insomnia medication) may require a lower dosage than men to avoid lingering sleepiness the next morning.
Dr Chellappa added: “Most of sleep and circadian interventions are a newly emerging field with limited research on sex differences. As we understand more about how women and men sleep, differences in their circadian rhythms and how these affect their metabolism, we can move towards more precise and personalised healthcare which enhances the likelihood of positive outcomes.”
The research was funded by the Alexander Von Humboldt Foundation, the US Department of Defense and the National Institute of Health.

A noninvasive brain stimulation treatment improved depression and anxiety symptoms among older adults in a new University of Florida-led study.
Improvements in depression and anxiety symptoms were greatest among patients who reported higher symptom levels before treatment. Among participants who experienced moderate to severe state anxiety — or anxiety associated with stressful situations or events — the treatment benefits persisted at a one-year followup.
The findings, published in the journal Brain Stimulation, suggest the treatment, known as transcranial direct current stimulation, or tDCS, holds promise as a noninvasive, drug-free option to treat depression and anxiety symptoms, which affect 1 in 4 older adults.
“Depression and anxiety can impact our overall mental health, cognitive function and ability to function independently as we age,” said the study’s senior author Adam Woods, Ph.D., the associate dean for research and a professor of clinical and health psychology at the UF College of Public Health and Health Professions and co-director of UF’s Center for Cognitive Aging and Memory Clinical Translational Research. “Often, front-line treatments involve medication and/or therapy, which can both be effective. However, there is also a pressing need for accessible and noninvasive options that can be deployed in people who are either nonresponsive to pharmaceutical treatment, unable to access or participate in clinic-based intensive treatment programs, or for a variety of other reasons.”
Treatment benefits in the UF-led study were seen among participants with subclinical depression and anxiety, meaning their symptoms may not meet the criteria for diagnosis. Yet, even subclinical depression and anxiety can be associated with cognitive decline in older adults, the researchers say.
The tDCS treatment is delivered by a safe and weak electrical current passed through electrodes placed on a person’s head. Researchers targeted the prefrontal cortex, an area of the brain associated with cognition and emotion regulation.
The new study was conducted as part of the National Institute on Aging-funded Augmenting Clinical Training in Older Adults Study, the largest study of its kind with older adults participating at UF and University of Arizona study sites. Nearly 400 older adults were randomly assigned to one of two groups: 12 weeks of tDCS paired with cognitive training designed to improve working memory and processing speed, or 12 weeks of cognitive training paired with a placebo version of tDCS.

Investigators also collected a wealth of data from cognitive, functional and neuroimaging tests as well as self-report measures of psychological symptoms, including depression and anxiety.
After controlling for factors such as prescription drugs that may impact depression and anxiety symptoms, the study team found that participants who received the tDCS treatment had significant improvements in mild depression and moderate to severe state anxiety, compared with the group that did not receive tDCS.
“Extensive research has demonstrated the efficacy of active stimulation to this area of the brain in reducing psychological symptoms in individuals with diagnosed psychiatric disorders,” said Hanna Hausman, the study’s lead author and a UF PHHP clinical psychology Ph.D. student in neuropsychology. “It was an unexpected yet welcome surprise to witness similar effects in our sample of older adults without significant psychiatric histories, especially on a large scale. Demonstrating this therapeutic effect is important because even subclinical depression and anxiety symptoms in older adults are associated with adverse outcomes.”
Next steps for this research should include a phase 3 randomized clinical trial designed to assess the effect of tDCS and cognitive training on anxiety among a large and diverse group of older adults, the investigators say. The Korea Food and Drug Administration has approved tDCS as an at-home treatment for depression for adults in South Korea, and with additional study, it could become an accessible and easy-to-use treatment in the U.S. once sufficient evidence is available for U.S. Food and Drug Administration approval.
“tDCS treatment is cost-effective, portable and can be seamlessly integrated with existing mental health therapies or used as a standalone intervention,” Hausman said. “Its potential for at-home self-administration would further expand accessibility and reduce personnel costs, making it a promising intervention for individuals who may experience barriers accessing face-to-face clinical care.”

One of the molecules responsible for triggering the inflammation that causes allergic respiratory diseases, such as asthma and allergic rhinitis, has just been discovered by scientists from the CNRS, Inserm and the Université Toulouse III — Paul Sabatier. This molecule, from the alarmin family, represents a therapeutic target of major interest for the treatment of allergic diseases. The study, co-directed by Corinne Cayrol and Jean-Philippe Girard, is published in the Journal of Experimental Medicine on 10 April.
The inflammation process plays a crucial role in allergic respiratory diseases, such as asthma and allergic rhinitis. Although the pulmonary epithelium, the carpet of cells that forms the inner surface of the lungs, is recognised as a major player in the respiratory inflammation that causes these diseases, the underlying mechanisms are still poorly understood.
A research team has identified one of the molecules responsible for triggering these allergic reactions, in a study co-led by two CNRS and Inserm scientists working at l’Institut de pharmacologie et de biologie structural (CNRS/Université Toulouse III — Paul Sabatier). This molecule from the alarmin family, named TL1A, is released by lung epithelium cells a few minutes after exposure to a mould-type allergen. It cooperates with another alarmin, interleukin-33, to alert the immune system. This double alarm signal stimulates the activity of immune cells, triggering a cascade of reactions responsible for allergic inflammation.
Alarmins, therefore, constitute major therapeutic targets for the treatment of respiratory allergic diseases. In a few years’ time, treatments based on antibodies blocking the TL1A alarmin could benefit patients suffering from severe asthma or other allergic diseases. In France, at least 17 million people are affected by allergic diseaseswith the most severe forms of asthma being responsible for several hundred deaths every year.

Using artificial intelligence (AI) to supplement radiologists’ evaluations of mammograms may improve breast-cancer screening by reducing false positives without missing cases of cancer, according to a study by researchers at Washington University School of Medicine in St. Louis and Whiterabbit.ai, a Silicon Valley-based technology startup.
The researchers developed an algorithm that identified normal mammograms with very high sensitivity. They then ran a simulation on patient data to see what would have happened if all of the very low-risk mammograms had been taken off radiologists’ plates, freeing the doctors to concentrate on the more questionable scans. The simulation revealed that fewer people would have been called back for additional testing but that the same number of cancer cases would have been detected.
“False positives are when you call a patient back for additional testing, and it turns out to be benign,” explained senior author Richard L. Wahl, MD, a professor of radiology at Washington University’s Mallinckrodt Institute of Radiology (MIR) and a professor of radiation oncology. “That causes a lot of unnecessary anxiety for patients and consumes medical resources. This simulation study showed that very low-risk mammograms can be reliably identified by AI to reduce false positives and improve workflows.”
The study is published April 10 in the journal Radiology: Artificial Intelligence.
Wahl previously collaborated with Whiterabbit.ai on an algorithm to help radiologists judge breast density on mammograms to identify people who could benefit from additional or alternative screening. That algorithm received clearance from the Food and Drug Administration (FDA) in 2020 and is now marketed by Whiterabbit.ai as WRDensity.
In this study, Wahl and colleagues at Whiterabbit.ai worked together to develop a way to rule out cancer using AI to evaluate mammograms. They trained the AI model on 123,248 2D digital mammograms (containing 6,161 showing cancer) that were largely collected and read by Washington University radiologists. Then, they validated and tested the AI model on three independent sets of mammograms, two from institutions in the U.S. and one in the United Kingdom.
First, the researchers figured out what the doctors did: how many patients were called back for secondary screening and biopsies; the results of those tests; and the final determination in each case. Then, they applied AI to the datasets to see what would have been different if AI had been used to remove negative mammograms in the initial assessments and physicians had followed standard diagnostic procedures to evaluate the rest.
For example, consider the largest dataset, which contained 11,592 mammograms. When scaled to 10,000 mammograms (to make the math simpler for the purposes of the simulation), AI identified 34.9% as negative. If those 3,485 negative mammograms had been removed from the workload, radiologists would have made 897 callbacks for diagnostic exams, a reduction of 23.7% from the 1,159 they made in reality. At the next step, 190 people would have been called in a second time for biopsies, a reduction of 6.9% from the 200 in reality. At the end of the process, both the AI rule-out and real-world standard-of-care approaches identified the same 55 cancers. In other words, this study of AI suggests that out of 10,000 people who underwent initial mammograms, 262 could have avoided diagnostic exams, and 10 could have avoided biopsies, without any cancer cases being missed.
“At the end of the day, we believe in a world where the doctor is the superhero who finds cancer and helps patients navigate their journey ahead,” said co-author Jason Su, co-founder and chief technology officer at Whiterabbit.ai. “The way AI systems can help is by being in a supporting role. By accurately assessing the negatives, it can help remove the hay from the haystack so doctors can find the needle more easily. This study demonstrates that AI can potentially be highly accurate in identifying negative exams. More importantly, the results showed that automating the detection of negatives may also lead to a tremendous benefit in the reduction of false positives without changing the cancer detection rate.”

The idea of growing a functioning human brain-like tissues in a dish has always sounded pretty far-fetched, even to researchers in the field. Towards the future goal, a Japanese and French research team has developed a technique for connecting lab-grown brain-mimicking tissue in a way that resembles circuits in our brain.
It is challenging to study exact mechanisms of the brain development and functions. Animal studies are limited by differences between species in brain structure and function, and brain cells grown in the lab tend to lack the characteristic connections of cells in the human brain. What’s more, researchers are increasingly realizing that these interregional connections, and the circuits that they create, are important for many of the brain functions that define us as humans.
Previous studies have tried to create brain circuits under laboratory conditions, which have been advancing the field. Researchers from The University of Tokyo have recently found a way to create more physiological connections between lab-grown “neural organoids,” an experimental model tissue in which human stem cells are grown into three-dimensional developmental brain-mimicking structures. The team did this by linking the organoids via axonal bundles, which is similar to how regions are connected in the living human brain.
“In single-neural organoids grown under laboratory conditions, the cells start to display relatively simple electrical activity,” says co-lead author of the study Tomoya Duenki. “when we connected two neural organoids with axonal bundles, we were able to see how these bidirectional connections contributed to generating and synchronizing activity patterns between the organoids, showing some similarity to connections between two regions within the brain.”
The cerebral organoids that were connected with axonal bundles showed more complex activity than single organoids or those connected using previous techniques. In addition, when the research team stimulated the axonal bundles using a technique known as optogenetics, the organoid activity was altered accordingly and the organoids were affected by these changes for some time, in a process known as plasticity.
“These findings suggest that axonal bundle connections are important for developing complex networks,” explains Yoshiho Ikeuchi, senior author of the study. “Notably, complex brain networks are responsible for many profound functions, such as language, attention, and emotion.”
Given that alterations in brain networks have been associated with various neurological and psychiatric conditions, a better understanding of brain networks is important. The ability to study lab-grown human neural circuits will improve our knowledge of how these networks form and change over time in different situations, and may lead to improved treatments for these conditions.