A promising therapy that treats blood cancers by harnessing the power of the immune system to target and destroy cancer cells could now treat solid tumors more efficiently. Thanks to a recent study published in Molecular Therapy — Methods & Clinical Development from Dan Cappabianca and Krishanu Saha at the Wisconsin Institute for Discovery, Chimeric Antigen Receptor (CAR) T-cell therapy can be improved by altering the conditions the T cells are grown in. And it was all discovered by chance.
T cells are white blood cells crucial for the immune system’s response to infections and cancer. They can be modified with CRISPR/Cas9 genome editing technology to express a specific receptor that redirects their natural “killing instincts” toward targeting cancer cells, specifically those in tumors. T cells can “remember” a pathogen after first exposure, allowing a quicker and stronger response if encountered again, like how vaccines train the immune system to recognize and fight off specific pathogens.
But for the cells to be used as a robust cancer treatment, they must be made in specific conditions in the lab.
“We were comparing two distinct T-cell media formulations with varying nutrient levels,” explains Cappabianca. “Interestingly, our breakthrough came entirely by chance. I inadvertently placed the cells in the wrong medium, which unexpectedly became the focal point of my entire thesis!” In the body, T cells develop from stem cells in the bone marrow. In the lab, researchers activate the T cells in a nutrient-deficient medium with low concentrations of glucose and glutamine which the cells need for energy. Then they move them to a high-nutrient medium. The first step stresses the cells and triggers specific processes that can enhance their ability to target tumors, promote the formation of T memory cells, and select the more resilient cells that can survive with such low levels of energy. The second step supports rapid growth and T cell multiplication.
The result of this “metabolic priming” was that treated cells retained their stem cell-like qualities, thus enhancing their ability to kill cancer cells, transform into durable memory cells, and survive longer in the body.
“We discovered that by briefly restricting sugar exposure, akin to a three-day ‘keto diet,’ our T cells showed reduced maturity at the end of the manufacturing process. The less mature they are when reinfused into a patient, the longer they live fighting cancer,” says Cappabianca.
The two-step process also appeared to help with cell memory. In CAR T-cell therapy, boosting these memory properties helps T cells better recognize and combat cancer over time.
In recent studies using T cells grown with the lab’s new approach, 63% of patients experienced a partial or complete reduction in tumors for a time. That’s an improvement from clinical trials using CAR T cells that were not grown with the lab’s two-step process where just 15% of patients experienced a partial or complete reduction in tumors after treatment.
More research is needed to understand the key factors that help these CAR T cells live longer and become effective against solid tumors. Looking ahead, researchers hope that this process of “metabolically priming” these specific kinds of CAR T cells can be adapted for large-scale manufacturing with the ultimate goal of treating patients within the next few years.
“A famous aphorism by French chemist, Louis Pasteur is that ‘chance favors only the prepared mind,'” says Saha. “Our unplanned media switch — really by chance — led us on a new path of discovery.”

A new study published this week shows how the global economy could claw back billions of dollars lost each year due to workplace injuries and illness.
In Australia, more than 500,000 employees sustain injuries or illnesses relating to work and in 60% of cases, this requires time off work. That equates to around $30 billion, equivalent to the annual output of Australia’s agricultural sector.
In Canada, their annual costs are equivalent (CAD $29.4 billion); the United Kingdom comes in at GBP £18.8 billion each year and across the European Union (EU), a staggering €467 billion a year.
New research published in Safety Science reveals that companies that offer healthy working conditions to employees, including supportive relationships with supervisors, valuing skills and job autonomy, and minimising work stress, report far fewer days lost per workers’ compensation claim.
Researchers from the University of South Australia’s Psychosocial Safety Climate Global Observatory compared working conditions in 100 Australian organisations to 12,000 injured workers’ compensation claims, identifying the root cause of delays in people returning to work after workplace-related injury or illness.
Organisations with a poor psychosocial safety climate (PSC) reported 160% more days off due to workplace injury or illness, compared to high PSC organisations (177 days vs 68 days).
Likewise, costs for the injury or illness were 104% greater in very low PSC organisations versus high PSC organisations ($67,260 vs $32,939 per employee).

“Our findings show that a healthy psychological climate in workplaces is essential if companies want to reduce working time loss and costs related to workplace injuries and illnesses,” says UniSA ARC Laureate Fellow Professor Maureen Dollard.
The researchers avoided individual bias by correlating data sets at the organisational level rather than surveys with injured employees on retrospective work conditions.
“Aside from a strong PSC, the most important factors in predicting a quicker return to work included how satisfying and rewarding their job was, how supportive their supervisor was, whether their skills were potentially adaptable, and how much autonomy they had in their role.”
In Australia, during 2017-18, an estimated 563,000 people had an injury or illness related to work, representing 4.2% of the workforce. In 60% of cases, this involved taking time off work, costing the equivalent of Australia’s annual agricultural output, or 1.6% of the nation’s GDP.
The most common occupations featured in the claims data included nurses, police officers and personal assistants. Muscle-related injuries comprised the bulk of the claims.
“These findings provide more evidence that ‘healthy’ workplaces matter,” says Prof Dollard. “They are not only important to our psychological health and to prevent injury to workers, but PSC is just as important following injury or illness.
“Building an organisation with strong PSC will help to reduce time lost and also cut costs through better injury prevention and management.”

Tumors arising in the base of the skull are among the most difficult to remove in neurosurgery. The current treatment method is to perform surgical removal by what is known as the microscopic anterior transpetrosal approach (ATPA). Seeking to lessen the risk of damage and postoperative complications, as the skull base is densely packed with nerves, blood vessels, and other tissues, not to mention the brain stem, an Osaka Metropolitan University medical research team is taking a new approach.
Led by Dr. Hiroki Morisako, a lecturer in the Graduate School of Medicine’s Department of Neurosurgery, and Professor Takeo Goto, who heads the department, the team has developed a minimally invasive surgical technique called a purely endoscopic subtemporal keyhole ATPA. The team members write in The Journal of Neurosurgery that this is, to their knowledge, the first time this procedure to remove lesions in the skull base region known as the petrous apex has been described in an article.
The endoscopic technique means a smaller area of the skull needs to be surgically opened compared to the microscopic approach, an average of only 11.2 cm² versus 33.9 cm². The risk of damage to the brain is also reduced.
The team performed 10 neurosurgeries using their method from 2022 to 2023 at Osaka Metropolitan University Hospital and compared the results to 13 surgeries using the microscopic ATPA from 2014 to 2021. In terms of operative time, the endoscopic approach reduced it noticeably, from an average of 410.9 minutes to 252.9 minutes. Similarly, blood loss lessened from a mean of 193 ml to 90 ml. The degree of tumor resection (surgical removal) was just as high as the microscopic method, while neurological functions were preserved at a rate equal to or higher than with the conventional approach.
“Comparison of the new endoscopic method and the conventional microscopic method showed no significant difference in tumor resection rate or in the ability to perform daily activities before and after surgery, with the new endoscopic approach resulting in shorter operative times and less blood loss,” Professor Goto stated. “The widespread use of this surgical procedure is expected to improve the treatment results of brain tumors in the base of the skull, not only in Japan but also worldwide.”

A new study in mice hints at the promise of an eventual alternative treatment option for the “wet” version of age-related macular degeneration (AMD).
Researchers determined in mice that an enzyme related to cell growth and division is a culprit in the blood vessel invasion in the back of the eye that causes blurred central vision in wet AMD. Targeting the enzyme, called telomerase, with an experimental drug suppressed abnormal vascular growth in the animals’ retina.
The only current treatment for wet AMD is injection into the eye of a medication that blocks the activity of a growth factor protein, called VEGF, which is also known to prompt formation of abnormal blood vessel growth in this condition.
“Anti-VEGF treatment has shortcomings — after two years, about half of people stop responding. And patients can develop scarring under the retina,” said senior study author Nagaraj Kerur, associate professor of ophthalmology and visual sciences in The Ohio State University College of Medicine.
“There is a need for better understanding of the mechanisms behind this problem, which, to me, means newer targets need to be tested.”
The study was published recently in the journal Biochimica et Biophysica Acta – Molecular Basis of Disease.
Dry age-related macular degeneration constitutes about 80% of all AMD cases, and occurs when the macula, a part of the retina, gets thinner, leading to buildup of proteins and cell death, which blur a person’s central vision.

Wet AMD, also known as neovascular AMD, is caused by the growth of new blood vessels that invade the retina, a space normally free of vascular activity.
“You don’t want to have blood vessels there,” said Kerur, who also has a faculty appointment in microbial infection and immunity at Ohio State. “And the blood vessels that invade are often not healthy — they leak their contents and cause inflammation.”
Previous cancer research has linked high activity of telomerase to rapid production and migration of cells lining blood vessels that enables tumor growth, and has also shown the enzyme can stimulate production of VEGF. Based on those findings, Kerur and colleagues sought in this study to see if telomerase could have a similar damaging effect in the eye.
A series of experiments first confirmed telomerase has a role in abnormal blood vessel formation in a mouse model of wet AMD. Researchers found that, compared to control mice, expression and activity of one of two genes carrying instructions for making telomerase were higher in the eyes of mice in which rapid growth of new blood vessels was induced with a laser.
In addition, the abnormal blood vessel response to laser injury was significantly lower in mice lacking both telomerase genes, “providing genetically clear evidence that telomerase plays a critical role in development of the disease,” Kerur said.
The team then tested the effects of an experimental compound that inhibits telomerase activity. They confirmed that the drug lowered telomerase activity in healthy mice, and found that injecting it into the eyes of mice with symptoms mimicking wet AMD significantly reduced the abnormal blood vessel invasion.

Telomerase’s job is to rebuild telomeres, which function as protective caps at the end of chromosomes. Telomeres are known to shorten in many types of cells as a consequence of aging, but Kerur said the study suggested localized blocking of telomerase in the eye had no bearing on the enzyme’s telomere-building function.
The experimental treatment’s effectiveness at curbing abnormal blood vessel growth in mice was similar to the current anti-VEGF treatment, Kerur said. But the researchers made an intriguing finding when testing both drugs at lower doses: Individually, a lower dose did not have much of a therapeutic effect, but a combination of both drugs at lower doses gave the best results of all.
“Possibly, one goal would be using a combination therapy rather than one alone,” Kerur said. “But telomerase inhibition by itself can also be pursued independently, and that is the plan.”
This work was supported by National Institutes of Health grants, the Ohio Lions Eye Research Foundation and a Research to Prevent Blindness grant.
Co-authors include Aman Kumar, Vinodhini Jayananthan, Asmaa Zidan, Tyler Heisler-Taylor and Shigeo Tamiya of Ohio State, and Yosuke Nagasaka and Jayakrishna Ambati of the University of Virginia.

Researchers have detected anaerobic and aerobic bacteria in commercial tattoo and permanent makeup inks. The findings, reported in Applied and Environmental Microbiology, a journal of the American Society for Microbiology, demonstrate that the inks could be a source of human infections. The new study is particularly notable as it is the first to investigate the presence of anaerobic bacteria in commercial tattoo inks.
“Our findings reveal that unopened and sealed tattoo inks can harbor anaerobic bacteria, known to thrive in low-oxygen environments like the dermal layer of the skin, alongside aerobic bacteria,” said corresponding author Seong-Jae (Peter) Kim, Ph.D., a microbiologist with the Division of Microbiology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Ark. “This suggests that contaminated tattoo inks could be a source of infection from both types of bacteria. The results emphasize the importance of monitoring these products for both aerobic and anaerobic bacteria, including possibly pathogenic microorganisms.”
The main goal of the new study was to assess the prevalence of both aerobic and anaerobic microbial contaminants in tattoo inks available on the U.S. market. For the detection of aerobic bacteria, the researchers mixed 1 to 2 grams of tattoo ink solution with appropriate media and incubated them in a standard incubator, and to detect anaerobic bacteria, they mixed the ink solution with appropriate media and incubated them in an anaerobic chamber, a device specifically designed to cultivate anaerobes. This chamber is kept oxygen-free by constant flushing with a mix of gases such as nitrogen, carbon dioxide and hydrogen. The researchers conducted this procedure for a total of 75 tattoo inks from 14 different manufacturers.
The investigators discovered that around 35% of tattoo or permanent makeup inks sold in the U.S. were found to be contaminated with bacteria. “Both types of bacteria, those needing oxygen (aerobic) and those not needing oxygen (anaerobic), can contaminate the inks,” Kim said. “There was no clear link between a product label claiming sterility and the actual absence of bacterial contamination.”
“The rising popularity of tattooing in recent years has coincided with an increase in tattoo-related complications or adverse reactions,” Kim said. “It should be noted that microbial infections constitute just one aspect of these complications. In addition to microbial infections, immunologic complications such as inflammatory reactions and allergic hypersensitivity, as well as toxic responses, represent a significant portion of these issues. In light of our study results, we want to emphasize the importance of continuously monitoring these products to ensure the microbial safety of tattoo inks.”
Kim and his colleagues will move their research forward in 2 key directions. They will develop more efficient microbial detection methods for tattoo inks, making the process quicker, more accurate and less labor-intensive. They will also conduct systematic research to deepen the understanding of microbial contamination in tattoo and permanent makeup inks. This will include studying the occurrence, co-occurrence and diversity of microbial contaminants, which is essential for preventing contamination in these products.

Good news for all the treadmill runners who suffer from stubborn and painful shin splints: A little outdoor gait training may help, new research suggests.
A randomized controlled trial found that four weeks of gait training outdoors, in addition to home exercises often prescribed for shin splints, led to improved running biomechanics even when the runners were using a treadmill. These improvements included decreasing the time the runners’ feet were in contact with the ground or treadmill, a recently identified contributor to shin splints.
Based on the trial results, the researchers, including UVA Health sports medicine expert David J. Hryvniak, DO, are recommending that clinicians begin including outdoor gait training as part of rehabilitation programs for patients struggling with chronic shin splints.
“This is an important finding for clinicians, as this gives us a tool to use to help these runners,” said Hryvniak, a running medicine specialist who is part of UVA Health’s Runner’s Clinic. “These gait-training cues can be an easy thing to add into a rehab program to help patients improve running mechanics that can underlie many common running injuries.”
Soothing Shin Splints
Affecting approximately 40% of all runners, shin splints typically begin as tenderness in the lower leg that goes away after exercising. But for regular runners, this pain can worsen and become persistent. In severe cases, shin splints can even lead to stress fractures.
Prior research has found that short courses of outdoor gait training can significantly reduce shin-splint pain for outdoor runners. But experts had been uncertain if these benefits would transfer to the flat, regular surface of treadmill running. That prompted an interdisciplinary team of researchers — from UVA’s College of Arts & Sciences, School of Education and School of Medicine, as well as Virginia Commonwealth University, Plymouth State University and the University of North Carolina at Chapel Hill — to launch a randomized trial to find out if outdoor gait training would benefit treadmill users.

The researchers enrolled 17 treadmill runners between ages 18 and 45 who ran at least three times a week and who had been suffering lower leg pain during or after running for at least a month. The volunteers were randomly divided into two groups: One group received four weeks of outdoor gait training and performed commonly prescribed home strengthening exercises, while the other group only performed the home exercises.
During the gait training, participants were provided with “vibrotactile feedback” -meaning they felt a little vibration — when special sensors in their shoes detected their feet were in contact with the ground for too long. This helped them improve their stride and gait to reduce this potential contributor to shin splints.
At the end of the study period, both groups saw strength improvements in their legs. But the gait trainers also had improved running technique, or what the researchers call “favorable adjustments in running gait mechanics.” And, sure enough, these gait improvements were seen during both outdoor runs and treadmill runs.
That suggests outdoor gait training could be an important new tool to help treadmill users work up a sweat pain-free, the researchers say.
“Shin splints are a very common running injury, especially with those who are new to the sport,” Hryvniak said. “These gait cues are something that have been shown to be an effective tool that patients can use literally ‘on the run.'”
Support for the research was provided by a Mid-Atlantic Athletic Trainers’ Association graduate student grant, a National Athletic Trainers’ Association doctoral dissertation grant (1920DGP01) and a UVA School of Education and Human Development IDEA grant.

In 2019, more than 12,000 new cases of cervical cancer were diagnosed and upwards of 4,000 patients died in the U.S. The causal link between human papillomavirus (HPV) infection and the development of cervical cancer is well documented. Cervical cancer screening guidelines are currently in the review process for updates. On May 15, 2024, the U.S. Food and Drug Administration (FDA) approved patient-collected testing (vaginal self-collection) for HPV. Several countries, including the Netherlands and Australia, have introduced HPV self-collection as a part of their national screening programs.
In a new study from Boston University Chobanian & Avedisian School of Medicine and the University of Hawaii at Manoa School of Nursing, researchers found more than half of healthcare providers would definitely or possibly offer HPV self-collection to their patients if the FDA approved the procedure, indicating substantial acceptance of this technology among the healthcare provider community.
“Healthcare providers felt that self-collection would be particularly beneficial for those who did not have access to clinician-collected screening, as well as for patients who may have difficulty with pelvic exams for any reason, such as those with history of trauma, sexual or gender minority patients and those with mobility issues,” explained senior author Rebecca B. Perkins, MD, MSc, professor of obstetrics & gynecology at BU and an obstetrician & gynecologist at Boston Medical Center.
This study incorporated a mixed methods design including conducting a national survey and interviews of healthcare providers who perform cervical cancer screening. Quantitative measures consisted of provider/practice characteristics, willingness to recommend and preferences related to self-collection. Interviews further elucidated the provider perspectives.
The study found that male providers, advanced practice providers, internal and family physicians, and those practicing in an academic medical center, hospital, or community health setting were more likely to support self-collection than female participants, OB-GYN physicians, and those in private practice.
“While we found providers considered HPV self-collection to be a way to expand access for patients, they also expressed concerns related to the quality of the sample in generating accurate results,” added Holly Fontenot, PhD, RN/NP, FAAN,professor of nursing at University of Hawaii and lead author of the study.
According to the researchers, the recent approval of HPV self-collection in the U.S. provides another option for cervical cancer screening, which can help reduce barriers related to access or to personal medical conditions.
These findings appear online in the journal Women’s Health Issues.
Funding for this study was supported in part by a research grant from American Cancer Society Award RSG19-011-01CPHPC.

People who have received solid organ transplants and take immunosuppressant medications to prevent rejection are among those most susceptible to the damaging effects of COVID-19, including breakthrough infections, severe illness, hospitalization and death. Particularly dangerous for them has been the XBB.1.5 subvariant of the omicron strain of SARS-CoV-2, the virus that causes COVID-19. That’s because XBB.1.5 possesses a genetic mutation that enables it to more effectively bind with cells it attacks, and therefore, make it more transmissible than earlier SARS-CoV-2 strains.
In a study published today in the journal Clinical Infectious Diseases, a Johns Hopkins Medicine research team reports that for XBB.1.5, there is good news for solid organ transplant recipients (SOTRs) and other immunocompromised people who receive regular booster doses of a messenger RNA (mRNA) bivalent vaccine (a vaccine designed to enhance immunity to a variety of SARS-CoV-2 strains).
“We found that a SOTR’s ability to neutralize XBB.1.5 wanes at about three months following the first bivalent booster shot, but improves with a second booster to about the previous level,” says study senior author Andrew Karaba, M.D., Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and an infectious diseases expert with the Johns Hopkins Transplant Research Center. “This indicates that repeated boosting within six months may play a role in reducing infections, particularly among populations at highest risk, such as SOTRs.”
Bivalent mRNA vaccines, such as the ones used in this study, introduce the body’s immune system to spike proteins found in different strains of SARS-CoV-2. Found on the surface of the virus, the spike protein enables the virus to latch onto healthy cells and infect them. Antibodies, produced by the immune system in response to spike proteins in a bivalent vaccine, neutralize the virus particles. This, in turn, prevents infection or, at least, reduces the severity of the disease.
“Previous studies have shown that for immunocompromised populations — such as SOTRs taking immunosuppressant medications to lower the risk of organ rejection — a single bivalent vaccine boosted virus neutralization, but the duration of that boost was unknown,” says study co-author William Werbel, M.D., Ph.D., also an assistant professor of medicine at the Johns Hopkins University School of Medicine and an infectious diseases expert with the Johns Hopkins Transplant Research Center. “What we wanted to learn was how long the boost lasted and if a second booster would build that immunity back up.”
The researchers studied 76 SOTRs who had received a minimum of three doses of a primary monovalent (active against just the original SARS-CoV-2 strain) mRNA vaccine, reported receiving either one or two bivalent mRNA vaccine boosters (containing both the original strain and the omicron BA.5 variant), and provided two or more blood samples that were obtained pre- and post-bivalent booster in one of three groups: 59 paired samples taken before and after the first booster, 31 paired samples taken before and after the second booster, and 14 paired samples taken before and after both boosters.
The study participants were generally middle age, more than five years post-transplant, and were kidney and/or liver transplant recipients. Fourteen had evidence of COVID-19 before the first booster, while 16 developed COVID-19 between the first booster and one month past the second.

The researchers found that the amount of circulating antibody and, in turn, virus neutralization, significantly increased by one month after the first bivalent booster for both the BA.5 and XBB.1.5 strains of SARS-CoV-2. However, this dropped sharply to nearly the pre-booster levels at three months, and even more so at six months.
Following a second bivalent booster, many SOTRs regained the ability to neutralize both virus strains; yet 42% did not have any detectable immunity to XBB.1.5. The researchers found that those SOTRs were more likely to be receiving corticosteroids as part of a three-drug immunosuppression regimen. They also discovered that, at nearly all times post-vaccinations (monovalent plus bivalent boosters), SOTRs with no prior SARS-CoV-2 infection showed poor XBB.1.5 neutralization, and at levels far below those who had hybrid (infection and vaccination) immunity.
“Our findings indicate that repeat boosting with omicron-containing vaccines may improve protection against COVID-19 among SOTRs, but more frequent boosting — every three to six months — appears necessary to maintain neutralizing ability against the more recent omicron subvariants, such as BA.5 and XBB.1.5,” says Karaba. “We believe this is especially important for SOTRs and other immunocompromised groups, and particularly for those who do not have hybrid immunity.”
Werbel adds that this practice is already showing benefit for another population at higher risk of SARS-CoV-2 infection, people age 65 or older.
“Our recommendation for immunocompromised groups is concordant with recent guidelines from the U.S. Centers for Disease Control and Prevention stating that people in this age group should get an additional updated vaccine at four months or longer from their last dose,” he says.
Along with Karaba and Werbel, the members of the study team from Johns Hopkins Medicine are Aura Abedon, Jennifer Alejo, Andrea Cox, Yolanda Eby, Snigdha Panda and Aaron Tobian, and study lead authors Camille Hage and Scott Johnston. The team also includes former Johns Hopkins Medicine transplant surgeon Dorry Segev, now with the NYU Grossman School of Medicine.
The work was supported by National Institute of Diabetes and Digestive and Kidney Diseases grant 5T32DK007713; National Institute of Allergy and Infectious Diseases grants K24AI144954, U01AI138897, 3U01AI138897, K08AI156021 and K23AI157893; the Ben-Dov family and the Trokhan Patterson family.
Werbel has received consulting and/or speaking fees from AstraZeneca, GlobalData, the China Medical Tribune and the Medical Learning Institute, and advisory board fees from AstraZeneca and Novavax. Karaba has received consulting fees from Hologic Inc. and speaking fees from PRIME Education. Segev reports receiving consulting and/or speaking honoraria from Sanofi, Novartis, Veloxis, Mallinckrodt, Jazz Pharmaceuticals, CSL Behring, Thermo Fisher Scientific, Caredx, Transmedics, Kamada, MediGO, Regeneron, AstraZeneca, Takeda/Shire, Novavax and Bridge to Life.
The other study authors do not have financial or conflict-of-interest disclosures.

A team from the Icahn School of Medicine at Mount Sinai has developed the most comprehensive epidemiological dataset for youth diabetes and prediabetes research, derived from extensive National Health and Nutrition Examination Survey (NHANES) data collected from 1999 to 2018. The dataset, revealed through the newly launched Prediabetes/diabetes in youth ONline Dashboard (POND), aims to ignite a new wave of research into the escalating issue of diabetes among young people.
The newly compiled dataset integrates data on 15,149 youths residing in the United States, aged 12 to 19, covering a range of variables from sociodemographic backgrounds to health statuses, dietary habits, and other lifestyle behaviors relevant to prediabetes and diabetes (preDM/DM). The POND portal invites researchers, health care professionals, and the public to explore these data, facilitating an understanding of factors that may influence youth diabetes risk.
“By providing a detailed view of the risk factors and trends associated with prediabetes and diabetes in our youth, this dataset empowers clinicians and researchers to develop more effective interventions tailored to the needs of this vulnerable population,” said Nita Vangeepuram, MD, MPH, Associate Professor of Pediatrics, Population Health Science and Policy, and Environmental Medicine and Climate Science at Icahn Mount Sinai, and clinical expert on the research team.
“The availability of such a comprehensive and accessible dataset is crucial for advancing our understanding of diabetes risk factors in youths,” added Gaurav Pandey, PhD, Associate Professor of Genetics and Genomic Sciences, and Artificial Intelligence and Human Health, and co-senior author of the study. “It allows researchers to apply advanced statistical and machine learning methods to uncover patterns underlying this serious disorder that were previously obscured due to a lack of publicly available comprehensive data.”
The development of the dataset and the POND web portal by co-first authors Yan Chak Li, MPhil, and Catherine McDonough, MS, underscores Mount Sinai’s commitment to accessible, actionable health data and to transparency of the methodology. By allowing users to interact with and analyze this comprehensive dataset, POND serves as a critical tool in the global fight against youth diabetes.
“Our findings have unveiled both established and novel variables linked to youth preDM/DM, emphasizing the hypothesis-generating value of this dataset and its potential to transform future research and develop targeted prevention strategies,” added Bian Liu, PhD, Associate Professor of Population Health Science and Policy, and Environmental Medicine and Climate Science, and co-senior author of the study. “It’s our hope that POND will not only foster more detailed studies, but also drive innovations in how we manage and prevent diabetes among younger populations.”
The urgency of this research is amplified by the anticipated rise in diabetes diagnoses among young people worldwide, marking a significant public health concern. The research team’s efforts to streamline and democratize access to critical health data through POND could lead to breakthroughs in how diabetes is understood and addressed in youth populations.
The study was funded by National Institutes of Health grant #s R21DK131555 and R01HG011407.

Cochlear implants, tiny electronic devices that can provide a sense of sound to people who are deaf or hard of hearing, have helped improve hearing for more than a million people worldwide, according to the National Institutes of Health.
However, cochlear implants today are only partially implanted, and they rely on external hardware that typically sits on the side of the head. These components restrict users, who can’t, for instance, swim, exercise, or sleep while wearing the external unit, and they may cause others to forgo the implant altogether.
On the way to creating a fully internal cochlear implant, a multidisciplinary team of researchers at MIT, Massachusetts Eye and Ear, Harvard Medical School, and Columbia University has produced an implantable microphone that performs as well as commercial external hearing aid microphones. The microphone remains one of the largest roadblocks to adopting a fully internalized cochlear implant.
This tiny microphone, a sensor produced from a biocompatible piezoelectric material, measures miniscule movements on the underside of the ear drum. Piezoelectric materials generate an electric charge when compressed or stretched. To maximize the device’s performance, the team also developed a low-noise amplifier that enhances the signal while minimizing noise from the electronics.
While many challenges must be overcome before such a microphone could be used with a cochlear implant, the collaborative team looks forward to further refining and testing this prototype, which builds off work begun at MIT and Mass Eye and Ear more than a decade ago.
“It starts with the ear doctors who are with this every day of the week, trying to improve people’s hearing, recognizing a need, and bringing that need to us. If it weren’t for this team collaboration, we wouldn’t be where we are today,” says Jeffrey Lang, the Vitesse Professor of Electrical Engineering, a member of the Research Laboratory of Electronics (RLE), and co-senior author of a paper on the microphone.
Lang’s coauthors include co-lead authors Emma Wawrzynek, an electrical engineering and computer science (EECS) graduate student, and Aaron Yeiser SM ’21; as well as mechanical engineering graduate student John Zhang; Lukas Graf and Christopher McHugh of Mass Eye and Ear; Ioannis Kymissis, the Kenneth Brayer Professor of Electrical Engineering at Columbia; Elizabeth S. Olson, a professor of biomedical engineering and auditory biophysics at Columbia; and co-senior author Hideko Heidi Nakajima, an associate professor of otolaryngology-head and neck surgery at Harvard Medical School and Mass Eye and Ear. The research is published today in the Journal of Micromechanics and Microengineering.

Overcoming an implant impasse
Cochlear implant microphones are usually placed on the side of the head, which means that users can’t take advantage of noise filtering and sound localization cues provided by the structure of the outer ear.
Fully implantable microphones offer many advantages. But most devices currently in development, which sense sound under the skin or motion of middle ear bones, can struggle to capture soft sounds and wide frequencies.
For the new microphone, the team targeted a part of the middle ear called the umbo. The umbo vibrates unidirectionally (inward and outward), making it easier to sense these simple movements.
Although the umbo has the largest range of movement of the middle-ear bones, it only moves by a few nanometers. Developing a device to measure such diminutive vibrations presents its own challenges.
On top of that, any implantable sensor must be biocompatible and able to withstand the body’s humid, dynamic environment without causing harm, which limits the materials that can be used.

“Our goal is that a surgeon implants this device at the same time as the cochlear implant and internalized processor, which means optimizing the surgery while working around the internal structures of the ear without disrupting any of the processes that go on in there,” Wawrzynek says.
With careful engineering, the team overcame these challenges.
They created the UmboMic, a triangular, 3-millimeter by 3-millimeter motion sensor composed of two layers of a biocompatible piezoelectric material called polyvinylidene difluoride (PVDF). These PVDF layers are sandwiched on either side of a flexible printed circuit board (PCB), forming a microphone that is about the size of a grain of rice and 200 micrometers thick. (An average human hair is about 100 micrometers thick.)
The narrow tip of the UmboMic would be placed against the umbo. When the umbo vibrates and pushes against the piezoelectric material, the PVDF layers bend and generate electric charges, which are measured by electrodes in the PCB layer.
Amplifying performance
The team used a “PVDF sandwich” design to reduce noise. When the sensor is bent, one layer of PVDF produces a positive charge and the other produces a negative charge. Electrical interference adds to both equally, so taking the difference between the charges cancels out the noise.
Using PVDF provides many advantages, but the material made fabrication especially difficult. PVDF loses its piezoelectric properties when exposed to temperatures above around 80 degrees Celsius, yet very high temperatures are needed to vaporize and deposit titanium, another biocompatible material, onto the sensor. Wawrzynek worked around this problem by depositing the titanium gradually and employing a heat sink to cool the PVDF.
But developing the sensor was only half the battle — umbo vibrations are so tiny that the team needed to amplify the signal without introducing too much noise. When they couldn’t find a suitable low-noise amplifier that also used very little power, they built their own.
With both prototypes in place, the researchers tested the UmboMic in human ear bones from cadavers and found that it had robust performance within the intensity and frequency range of human speech. The microphone and amplifier together also have a low noise floor, which means they could distinguish very quiet sounds from the overall noise level.
“One thing we saw that was really interesting is that the frequency response of the sensor is influenced by the anatomy of the ear we are experimenting on, because the umbo moves slightly differently in different people’s ears,” Wawrzynek says.
The researchers are preparing to launch live animal studies to further explore this finding. These experiments will also help them determine how the UmboMic responds to being implanted.
In addition, they are studying ways to encapsulate the sensor so it can remain in the body safely for up to 10 years but still be flexible enough to capture vibrations. Implants are often packaged in titanium, which would be too rigid for the UmboMic. They also plan to explore methods for mounting the UmboMic that won’t introduce vibrations.
“The results in this paper show the necessary broad-band response and low noise needed to act as an acoustic sensor. This result is surprising, because the bandwidth and noise floor are so competitive with the commercial hearing aid microphone. This performance shows the promise of the approach, which should inspire others to adopt this concept. I would expect that smaller size sensing elements and lower power electronics would be needed for next generation devices to enhance ease of implantation and battery life issues,” says Karl Grosh, professor of mechanical engineering at the University of Michigan, who was not involved with this work.
This research was funded, in part, by the National Institutes of Health, the National Science Foundation, the Cloetta Foundation in Zurich, Switzerland, and the Research Fund of the University of Basel, Switzerland.