Publisher Health

A Johns Hopkins Children’s Center study of children and youth with diabetes concludes that so-called autonomous artificial intelligence (AI) diabetic eye exams significantly increase completion rates of screenings designed to prevent potentially blinding diabetes eye diseases (DED). During the exam, pictures are taken of the backs of the eyes without the need to dilate them, and AI is used to provide an immediate result.
The study noted that the AI-driven technology used in the exams may close “care gaps” among racial and ethnic minority youth with diabetes, populations with historically higher rates of DED and less access to or adherence with regular screening for eye damage.
In a report on the study published Jan. 11 in Nature Communications, investigators examined diabetic eye exam completion rates in people under age 21 with type 1 and type 2 diabetes, and found that 100% of patients who underwent AI exams completed the eye assessment.
DED primarily refers to diabetic retinopathy, a potentially blinding complication of diabetes that occurs when poorly controlled sugar levels cause the overgrowth of, or damage to, blood vessels and nerve tissues in the light-sensitive retina at the back of the eye. According to the study researchers, retinopathy affects between 4% and 9% of youth with type 1 diabetes, and 4% to 15% of youth with type 2 diabetes. About 238,000 children, adolescents and young adults under age 20 are estimated to have diagnosed diabetes, according to the American Diabetes Association. Frequent screenings for DED facilitate early detection and treatment, and can help prevent progression of DED.
Generally, diabetes specialists and eye doctors recommend annual screenings, which typically require an additional, separate visit to an eye care provider, such as an optometrist or ophthalmologist, and the use of drops to dilate the pupil so that a clear view of the retina is visible through specialized instruments. However, studies show only 35% to 72% of youth with diabetes undergo recommended screenings, with even higher care gap rates among minority and poor youth. Previous studies also show that barriers to screenings include confusion about the need for screenings, inconvenience, and lack of time, access to specialists and transportation.
Previous studies by Risa Wolf, M.D., a pediatric endocrinologist at Johns Hopkins Children’s Center, and her team have found autonomous AI screening that uses cameras produce results that enable accurate DED diagnosis.
In the new study, researchers enrolled 164 participants, ranging in age from 8 to 21 years and all from the Johns Hopkins Pediatric Diabetes Center, between Nov. 24, 2021, and June 6, 2022. Some 58% were female and 41% were from minority groups (35% Black; 6% Hispanic). Some 47% of participants had Medicaid insurance. The subjects were randomly assigned to one of two groups. A group of 83 patients received the standard screening instructions and care, and were referred to either an optometrist or ophthalmologist for an eye exam. A second group of 81 patients underwent a five-to-10-minute autonomous AI system diabetic eye exam during a visit to their endocrinologist (the specialists who typically care for people with diabetes), and received their results at the same visit.

The AI system takes four pictures of the eye without dilation, and runs the images through an algorithm that determines the presence or absence of diabetic retinopathy, Wolf says. If it is present, a referral is made to an eye doctor for further evaluation. If it is absent, “you’re good for the year, and you just saved yourself time,” she adds.
Researchers found that 100% of patients in the group offered the autonomous AI screening completed their eye exam that day, while 22% of patients from the second group followed through within six months to complete an eye exam with an optometrist or ophthalmologist. The researchers found no statistical differences based on race, gender or socioeconomic status for whether participants in the second group scheduled the separate screening with an eye doctor.
The researchers also found that 25 out of 81 participants, or 31%, in the autonomous AI group had a result indicating that DED was present. Sixteen of those participants, or 64%, followed through in scheduling a secondary appointment with an eye care provider. Further analysis showed those who did not schedule the appointment were more likely to be Black and have Medicaid insurance.
“With AI technology, more people can get screened, which could then help identify more people who need follow-up evaluation,” says Wolf. “If we can offer this more conveniently at the point of care with their diabetes doctor, then we can also potentially improve health equity, and prevent the progression of diabetic eye disease.”
The investigators caution that the autonomous AI used in their study is not approved by the U.S. Food and Drug Administration for those under 21 years old. And they say a potential source of bias in the study was that some of the participants were familiar with autonomous AI diabetic eye exams from a prior study, and therefore may have been more willing to participate in the new one.
Along with Wolf, the study authors from Johns Hopkins include Alvin Liu, Anum Zehra, Lee Bromberger, Dhruva Patel, Ajaykarthik Ananthakrishnan, Elizabeth Brown, Laura Prichett and Harold Lehmann. Other authors are Roomasa Channa from University of Wisconsin and Michael D. Abramoff from the University of Iowa.
The study was funded by the National Eye Institute of the National Institutes of Health (Award Number R01EY033233) and the Diabetes Research Connection.
The authors associated with The Johns Hopkins University declared no conflicts of interest related to this press release.

As they grow, children increasingly focus their attention on social elements in their environment, such as faces or social interactions. However, children with autism are often more interested in non-social stimuli, such as textures or geometric shapes. By tracking where children look while viewing a cartoon, a team from the University of Geneva (UNIGE) has revealed that attention in autistic children does not follow the same developmental trajectory as that of typically developing children. Instead, they each gradually develop their own unique attentional preferences. These results, published in eLife, argue in favour of early interventions aimed at enhancing social attention, which could help guide autistic children onto developmental courses more akin to their peers, paving the way for tailored, individualized support.
Right from birth, babies are endowed with innate abilities that are crucial for their survival and adaptation. Among these innate abilities is a complex attentional system, finely tuned to detect the presence of others. Thus, from the very beginning of their lives, newborns show fascination for faces and face-like configurations, especially moving ones. Such preference for biological movement early in life is vital for development, serving as the primary driver of exploration and interaction with the environment, eventually setting the stage for more complex social interactions.
This fundamental, widely shared social attention can, however, be impaired in children with autism spectrum disorders (ASD). This highly diverse neurodevelopmental condition is characterized by repetitive behaviors and specific interests accompanied by significant challenges in communication and social interactions.
Eye-tracking
Are these social challenges expressed in the same way in all children with ASD? Do they vary according to the intensity of the disorder and/or age? Using an eye-tracking device that records eye movements in real time, a UNIGE team analysed the visual preferences of 166 children with ASD and 51 typically developing children (TD) while they freely viewed a short cartoon. The participants, all boys for sample homogeneity, ranged from two to seven years old, and were repeatedly tested as they developed.
”Each child watched a three-minute cartoon featuring a little donkey in various social situations, without any specific instructions. This was not a cartoon specially designed for our study, but rather one that is very popular among children in this age group,” explains Nada Kojovic, a postdoctoral scholar in the Department of Psychiatry at the UNIGE Faculty of Medicine and first author of the study.
Desynchronised attention in ASD
Typically developing children are observed to focus their attention on social interactions between characters, and as they grow older, to increasingly look at the very same social elements in a scene. This phenomenon of ”synchronisation” observed in typically developing children is absent in ASD children. The latter show an interest in other types of stimuli — such as objects or certain irregularities in the cartoon scenery — and over time each ASD child develops his or her own unique visual preferences.

”It is likely that we could identify sub-groups with common preferences among ASD children, but there is no real synchronisation of attention over the course of their development, unlike what is observed in TD children. This is the first time that a study has highlighted this developmental phenomenon,” states Daphné Bavelier, a full professor in the Psychology Section of the UNIGE’s Faculty of Psychology and Educational Sciences, and a co-author of the study.
The researchers also observed that the autistic children whose gaze was most alike that of typically developing ones function better in everyday life and have better cognitive skills. And crucially, the way in which a child views a social scene, such as the cartoon used here, can be used to predict future social difficulties.
In favour of early intervention
”These findings show how important it is for therapeutic interventions to target social attention at a very early stage in ASD children, especially those with the greatest developmental delay. Indeed, this work shows that if autistic children do not show interest in social interactions early on, they will become increasingly disinterested in them,” explains Marie Schaer, associate professor in the Department of Psychiatry at the UNIGE Faculty of Medicine, who led this research.
Moving forward, the UNIGE research team plans to apply its eye-tracking method to evaluate children who have benefited from a behavioural intervention known as the Early Start Denver Model (ESDM). This intensive behavioural intervention, developed in the United States, is designed to enhance communication skills in young autistic children through playful interactions. Since 2012, over a hundred autistic children under the age of three have benefited from this method in Geneva, showing encouraging outcomes. The researchers hope that their innovative eye-tracking technique will shed light on how this behavioural intervention contributes to the progress of ASD children, providing a unique tool to to improve on strategies for supporting their development.

As global life expectancies rise, the World Health Organization projects that by 2050, the global population aged 60 years and older will double to 2.1 billion from 1 billion in 2020 — a trend particularly notable in Japan, which has the highest percentage of people aged 65 years and older. In 2022, 29.1% of the population was 65 years or older (expected to rise to 34.8% by 2040). The increase in the aging population comes with new health challenges, such as the need to assess muscular health.
“The loss of muscle mass and strength could lead to a higher risk of falls, inactivity, confinement to bed, and metabolic problems,” says Professor Ryota Akagi from Shibaura Institute of Technology, who has been researching ways to quickly and non-invasively measure muscle response and coordination.
Now, Prof. Akagi, along with Dr. Kosuke Hirata from the University of Tsukuba; Dr. Yosuke Yamada from the National Institutes of Biomedical Innovation, Health and Nutrition; and Dr. Tsukasa Yoshida from the National Institutes of Biomedical Innovation have shown that bioelectrical impedance analysis (BIA), a technique widely used to assess body composition can also be used for measuring voluntary and evoked muscle contractions, which are integral to our ability to move, maintain stability, and respond to external stimuli. Their study lays the foundations for a convenient muscular health monitoring system; the corresponding findings were published on 23 November 2023 in Volume 14 of the journal Frontiers in Physiology.
BIA involves sending a safe electrical current through the body and measuring the impedance, characterized by resistance and reactance, where higher water and electrolyte concentrations lead to lower resistance and healthy cell membranes show higher reactance; these components are represented as phase angles calculated as a ratio of reactance and resistance [arctangent (reactance/resistance) × (180°/π)], where larger angles indicate higher muscle content.
To explore if the phase angle can serve as an indicator for other neuromuscular factors, the researchers examined its relationship with the neuromuscular properties of the leg, including a rapid force generation ability, intrinsic contractile properties, and overall neuromuscular activity in the plantar flexors of 60 participants aged 21-83 years.
Plantar flexors are a group of muscles located in the calf region and are essential for walking, running, jumping, and maintaining balance. “We aimed to clarify the association of phase angle obtained from the leg using BIA with voluntary muscle strength, twitch contractile properties, and neuromuscular activity,” says Assistant Prof. Hirata.
Muscle strength is the maximum force that muscles can generate during a voluntary contraction, while twitch contractile refers to how a muscle responds to an electrical stimulus. These measurements represent the ability of a muscle to contract, generate force, and contribute to movement. The findings revealed that the leg phase angle could estimate muscle contractile properties. Individuals with larger phase angles had better muscle function and generated more force. However, the researchers did not observe any between phase angle and neuromuscular activity.
These results indicate that the phase angle can be a valuable tool for estimating muscular health among individuals — such a system could find use in weight scales for a quick and easy physical assessment.
“Because phase angle can be measured even by impedance analyzer for home use, such as weighing scales with body composition analyzer, phase angle may be the way to monitor muscular health easily and quickly. If possible, segment-level phase angle measurement can be conducted even by impedance analyzer for home use,” says Prof. Akagi.
As the population ages and conditions like sarcopenia, involving muscle loss, become more prevalent, insights into muscular health will assist individuals in taking proactive measures and enable countries to develop policies prioritizing the muscular health of the older population.

Researchers at The University of Texas at El Paso have identified a novel pharmaceutical compound that successfully kills leukemia and lymphoma cancer cells, potentially paving the way for new forms of therapy.
Renato Aguilera, Ph.D., a professor in the Department of Biological Sciences, is the principal investigator on the project that identified the promising compound, called thiophene F-8. His team’s findings were recently published in the research journal PLOS One.
“The main goal of my research is to discover new anticancer drugs that can eventually treat distinct cancer types,” Aguilera explained. “This research not only had amazing results, it also led to the training of five Ph.D. students who are now working as postdoctoral fellows in research laboratories across the nation.”
Leukemia is a cancer of the blood cells while lymphoma is a cancer of the immune system. As part of their research into potential treatment of these cancers, Aguilera’s lab screened drug compounds to determine their impact on various cancer cell types. Pharmaceutical companies generate millions of compounds and their full range of uses is often unclear or unknown, Aguilera said. Some of these companies sell the generated compounds as chemical libraries, which researchers like Aguilera can then study to determine the precise effect of the compounds on human cells.
“The hardest part of this kind of research is figuring out what exactly a drug does,” said Aguilera who also serves as director of the Research Infrastructure Core of UTEP’s Border Biomedical Research Center.
As part of the project, the UTEP team tested 1,300 different compounds on cultures of human cancer cells. Thiophene F-8 was very successful at inducing programmed cell death in the leukemia and lymphoma cells, essentially sending a message to the cells causing them to kill themselves and inhibiting the growth of new cancer cells.
Mia Swain, Ph.D., helped discover and conduct research on thiophene F-8 as a doctoral student at UTEP. Swain graduated from UTEP in December of 2022 with a doctoral degree in biological sciences and is currently a postdoctoral fellow at Texas Tech University Health Sciences Center El Paso.
“Engaging in such a groundbreaking discovery has been truly fulfilling,” Swain said. “The compound’s potential to work in conjunction with existing therapies could be life-changing for leukemia and lymphoma patients.”
The UTEP team will continue studying the effectiveness of Thiophene F-8. If the drug is successful in further testing, Aguilera said, pharmaceutical companies may one day launch clinical studies to determine the compound’s effect on patients.

Wastewater surveillance is a potent tool in understanding COVID-19 transmission within school settings, according to a ground-breaking study led by epidemiologist David Larsen from Syracuse University.
The research team’s work that was published recently in PLOS Global Public Health establishes the pivotal role of wastewater analysis in managing the public health response to COVID-19 at schools.
The study focused on a middle and high school campus in Jefferson County, New York, serving 600 students and compared results from wastewater surveillance to COVID-19 case trends. The surveillance demonstrated high levels of sensitivity, positive predictive value (PPV), and negative predictive value (NPV) in wastewater surveillance. While the specificity of wastewater surveillance at the school was observed to be lower, the strong correlation between the amount of SARS-CoV-2 RNA recovered in wastewater and COVID-19 cases highlighted its potential in understanding transmission risk within the school.
“By analyzing wastewater samples, we observed a robust correlation between SARS-CoV-2 RNA levels and the number of confirmed COVID-19 cases within the school, providing critical insights into potential transmission,” says research team member Haley Kappus-Kron, an epidemiologist at the CDC Foundation.
The published study acknowledges the limitations of a one-day lead time of wastewater surveillance to predict clinical COVID-19 cases.
“The practicality of wastewater surveillance as an early warning tool heavily relies on timely reporting and swift actions following a positive sample,” says Kappus-Kron. “Nevertheless, in the absence of mass asymptomatic testing, wastewater surveillance presents an appealing and cost-effective approach to understand disease trends within school environments.”
While wastewater surveillance would not prevent all transmission, its role in understanding the extent of transmission could be critical in ensuring schools stay open as much as possible during a public health emergency due to an infectious disease. Applying wastewater surveillance in schools could potentially prevent unnecessary school closures and keep children in school longer.
“Wastewater surveillance will probably work for most infectious diseases, including the next public health emergency threat. With wastewater surveillance in schools, we may be able to keep the schools open longer and respond specifically to outbreaks rather than implement broad closures,” says Larsen, Professor and Chair of the Department of Public Health at Syracuse University’s Falk College of Sport and Human Dynamics who at outset of COVID in 2020 led an interdisciplinary team of experts in coordination with the New York State Department of Health to create a wastewater surveillance system throughout New York State.
As the world moves beyond the COVID-19 pandemic, schools may consider integrating wastewater surveillance into their emergency preparedness plans. The study advocates for school-specific plans that include access points, laboratory contacts, and protocols for effective wastewater sampling and analysis, especially during public health emergencies.

A newly developed PET imaging agent has been found to be effective in identifying medullary thyroid cancer (MTC) in preclinical and clinical studies, according to research published in the January issue of The Journal of Nuclear Medicine. The results of the studies indicate that the PET imaging agent may be a promising theranostic candidate for clinical use.
MTC is one of the rarest forms of thyroid cancer and accounts for approximately three percent of all cases. Since MTC originates from different cells than most thyroid cancers, different imaging and therapy targets are needed for these patients.
“The cholecystokinin-2 receptor (CCK-2R) is overexpressed on most MTC cells and various compounds targeting CCK-2R have been developed over the past several years. Most of these compounds, however, have low metabolic stability, which is not ideal for radioligand therapy,” noted Thomas Günther, PhD, pharmaceutical radiochemist at Stanford University in Stanford, California. “With a simplistic design modification to tackle instability issues, our team created multiple theranostic agents and sought to evaluate their effectiveness.”
In the study, three compounds (DOTA-CCK-66, DOTA-CCK 66.2, and DOTA-MGS5 external reference]) were each labeled separately with 64Cu, 67Ga, and 177Lu. CCK-2R affinity of each of the radiolabeled compounds was examined on MTC cells. All three compounds exhibited a high affinity, however, due to the more favorable in vitro properties overall of DOTA-CCK-66, DOTA-CCK-66.2 was excluded from further studies.
Next, in vivo stability, biodistribution, imaging, and competition studies were performed on mice bearing a CCK-2R-expressing tumor. 68Ga-DOTA-CCK-66 was selected for proof-of-concept PET/CT application based on its overall in vitro and in vivo properties.
Two MTC patients then underwent 68Ga-DOTA-CCK-66 PET/CT. The compound was well tolerated, showed a favorable biodistribution, and demonstrated high accumulation of activity in tumors.
“Due to increased in vivo stability, our compound reveals favorable tumor uptake as well as an improved activity clearance from off-target tissues. This could result in enhanced lesion detection in PET imaging and additionally enable targeted MTC radioligand therapy,” said Constantin Lapa, MD, director of nuclear medicine at University Hospital Augsburg, in Augsburg, Germany.
Günther and Lapa added, “A significant outcome of our work is the notion that it is possible to optimize pharmacokinetics by chemical design. Analyzing weaknesses of existing compounds and then systematically addressing those to improve imaging and treatment is crucial for future clinical translation.”
This research was published online in November 2023.
The authors of “Preclinical Evaluation of Minigastrin Analogs and Proof-of-Concept [68Ga]Ga-DOTA-CCK-66 PET/CT in 2 Patients with Medullary Thyroid Cancer” include Thomas Günther, Nadine Holzleitner, Roswitha Beck, and Hans-Jürgen Wester, Department of Chemistry, Chair of Pharmaceutical Radiochemistry, TUM School of Natural Sciences, Technical University of Munich, Garching, Germany; and Oliver Viering, Georgine Wienand, Alexander Dierks, Christian H. Pfob, Ralph A. Bundschuh, Malte Kircher, and Constantin Lapa, Nuclear Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany.

The protein HOXA9 is overexpressed in most acute myeloid leukemia (AML) cases and is associated with poor patient outcomes. However, HOXA9 is a difficult protein to target therapeutically, so researchers at St. Jude Children’s Research Hospital looked for ways to extinguish it indirectly. Using CRISPR/Cas9 screening, the researchers identified RBM5, demonstrating a causative link between RBM5 expression and leukemia cell proliferation. This link is driven by a novel dual function of RBM5 as both a DNA and RNA handler in gene expression. The research was published today in Genome Biology.
Overexpression of the protein HOXA9 is a hallmark of AML, present in over 70% of cases, often with poor prognosis. While this would implicate it as a useful drug target, the protein’s role as a transcription factor has left it “undruggable” because a drug that interferes with HOXA9 would likely have numerous other off-target effects. This inspired researchers to approach the problem from a different angle by investigating the proteins HOXA9 works alongside and relies on to function. Chunliang Li, PhD, St. Jude Department of Tumor Cell Biology, co-corresponding author on this paper, is one such researcher. Through his recent work devising an unbiased CRISPR screening strategy to identify targets of HOXA9, he uncovered a network of opportunities.
“This has been a continued effort since my lab was established in 2017,” said Li, “We built up this unique reporter system in early 2019, which is the first reporter authentically representing HOXA9 expression in these leukemia systems.”
The CRISPR/Cas9 screening approach is elegantly simple in design but incredibly effective. It involves attaching a fluorescent tag to the HOXA9 gene and inserting it into leukemia cell lines. This enables researchers to track differences in expression levels by looking at fluorescence in cells.
“We wanted to identify a more targetable or novel regulator. So, we conducted an unbiased whole genome CRISPR screening to target all the genes expressed in cells,” Li stated. This allowed the researchers to examine different pathways where HOXA9 left its fluorescent fingerprint.
To the researchers’ surprise, splicing factors appeared to be the most represented pathway.
“This was quite surprising to us because splicing factors regulate different combinations of the transcript, but not usually the level. Our data suggested these proteins control the HOXA9 expression level,” said Li. “So, we hypothesized maybe the splicing factors have another function, like a dual function.”
The protein that stood out was the RNA-binding protein RBM5. The researchers found that RBM5 is highly expressed in leukemia cells as opposed to other cell types and that both the DNA- and RNA-binding sites are vital to its oncogenic functions. While the RBM family comprises vital RNA splicing factors, their function in DNA transcription was unknown. To address the direct transcriptional regulation of RBM5/HOXA9, the researchers generated a system to allow the acute degradation of RBM5.

“Immediately after RBM5 protein was removed from cells, HOXA9 mRNA levels were significantly reduced,” Li explained, “This reduction happened as early as two hours later but did not impact splicing events of HOXA9.” Additionally, leukemia cells stripped of their ability to produce RBM5 were rescued through overexpression of HOXA9, further demonstrating the link between the two proteins.
These results have Li looking to explore the protein as a drug target to treat AML.
“We think RBM5 is a very good dependency gene, which should be a good target based on our functional assays,” he said. “If we can specifically target the DNA binding affinity of these proteins, we should be able to combine with other existing therapies in synergy to target HOXA9-driven leukemia.”
Authors and funding
The study’s first author is Mengli Zhang, Soochow University. The co-corresponding author is Peng Xu, Soochow University. Other authors include Judith Hyle, Shaela Wright, Zhenling Liu, Wojciech Rosikiewicz, Beisi Xu and Liusheng He of St. Jude; Xiaowen Chen of Shenzhen Children’s Hospital; Ye Xin, Yingcai Jin, Jianxiang Zhang, Xue Yang and Xinfeng Chen of Soochow University; Hong Liu, Nana Ping and Depei Wu of The First Affiliated Hospital of Soochow University; and Feiqiu Wen of Shenzhen Children’s Hospital.
The study was initially supported by grants from ALSAC, the fundraising and awareness organization of St. Jude.

A groundbreaking 3D, three-layer nanomatrix vascular sheet that possesses multiple features of atherosclerosis has been applied for developing a high-throughput functional assay of drug candidates to treat this disease, University of Alabama at Birmingham researchers report in the journal Biomaterials.
“Current in vitro atherosclerosis models have significant limitations, including the lack of three-layer vascular architecture and limited atherosclerotic features,” said Ho-Wook Jun, Ph.D., a professor in the UAB Department of Biomedical Engineering and the corresponding author. “Moreover, no scalable 3D atherosclerosis model is available for the evaluation of potential therapeutics via high-throughput assays.”
Cardiovascular disease — primarily caused by atherosclerosis — is the leading cause of death in the United States. In the development of effective therapies for atherosclerosis, in vitro models are commonly utilized to assess the efficacy and safety of novel therapeutics before proceeding to complex in vivo and clinical studies.
Recently, the United States Food and Drug Agency Modernization Act 2.0 has permitted the use of alternative models other than animals for drug testing before progressing to human trials. This transformative change in regulations serves as a driving force, inspiring the pursuit of advanced in vitro models, such as cell-based assays and organoid- or artificial intelligence-based models that are capable of replacing or reducing animal use in assessing drug efficacy and safety. The goal is to expedite progression from preclinical research to human clinical trials via a more efficient and cost-effective drug development process.
The novel in vitro 3D, three-layer nanomatrix vascular sheet with critical atherosclerosis multi-features, or VSA, includes endothelial cell dysfunction, monocyte recruitment, presence of macrophages, extracellular matrix remodeling, smooth muscle cell phenotype transition, inflammatory cytokine secretion, foam cells and calcification initiation. The VSA thus provides a human atherosclerosis-mimicking environment for drug evaluation.
The three layers of the robust vascular sheet, or VS, structure are composed of: 1) human aortic endothelial cells, 2) human aortic smooth muscle cells and 3) human aortic adventitial fibroblasts layers. These mimic the layered structure of the native vascular wall, which, from inside out, is composed of the tunica intima, tunica media and tunica adventitia tissues. The researchers created the critical atherosclerosis multi-features by adding monocytes and various pro-atherosclerotic cytokines, colony-stimulating factors and oxidized low-density lipoprotein to stimulate atherogenesis on the 3D, layered nanomatrix vascular sheet.
Co-first author Jun Chen, Ph.D., and colleagues used this VSA system to create high-throughput functional assays by fabricating multiple VSAs in 48-well plates. The VSAs were subjected to drug treatments and then were comprehensively characterized, with a focus on evaluating foam cells, inflammation and atherosclerosis-associated genes.

High-throughput functional assays were validated using two classic atherosclerosis drugs, rosuvastatin and sirolimus, and were used to evaluate two drug candidates, curcumin and colchicine, and a potential gene therapy candidate, microRNA-146a-loaded liposomes, for treating atherosclerosis. The researchers found that the VSAs replicated a number of results seen by others in in vivo tests of these treatments. “The high efficiency and scalability of the VSA-evaluated functional assays should facilitate drug discovery and development for atherosclerosis,” Chen said.
“Our study focuses on demonstrating the use of VSAs as a cost-effective and efficient way to investigate therapeutic effectiveness,” Jun said. “The VSAs offer a high-throughput methodology and allow for a relatively large number of biological replicates, also making them ideal for mechanistic research. For instance, VSAs can be customized to induce atherosclerosis on single-, double- or three-layer structures, which provides insights into the effect of discrete layers on atherogenesis, particularly the fibroblast layer. Furthermore, the vascular sheets can be scaled up to develop high-throughput assays for drug safety testing, helping determine pharmacological and toxicological parameters for use in animal models.”
The Birmingham-based Endomimetics, LLC, has licensed the new 3D, three-layer nanomatrix vascular sheet atherosclerosis model technology through UAB’s Bill L. Harbert Institute for Innovation and Entrepreneurship, which manages university intellectual property.
“The atherosclerosis drug market is a large and growing segment of the pharmaceutical industry,” said Joseph Garner, Ph.D., CEO of Endomimetics. “This market is experiencing significant growth due to the rising prevalence of cardiovascular diseases, advancements in pharmaceutical research and the development of innovative atherosclerosis treatments. By 2032, this market is projected to reach $26.9 billion with a 2.8 percent compound annual growth rate from 2023 to 2032. North America currently holds the dominant market share at more than 41 percent.”
Brigitta Brott, M.D., a co-author and an interventional cardiologist and professor in the UAB Department of Medicine Division of Cardiovascular Disease, said, “Endomimetics and UAB will collaborate with pharmaceutical companies to evaluate potential candidates for atherosclerosis treatment, utilizing our VSA-based efficacy and safety assays. This approach can also be extended to assess other drugs for conditions such as diabetes, obesity and liver-related diseases, where atherosclerosis is prevalent among many patients.”
Endomimetics anticipates providing this innovative atherosclerosis model this spring for evaluating various types of potential therapeutics. “Our atherosclerosis assays will pave the way for therapeutic candidates directly targeting human plaque and the atherosclerotic artery wall, and they will generate extensive predictive data on their responses, which is crucial for defining the therapeutic window of these candidates and providing essential groundwork for future studies,” Jun said.

At Endomimetics, Jun is chief scientific officer and Brott is chief medical officer.
Co-authors with Jun, Chen and Brott in the study, “Atherosclerotic three-layer nanomatrix vascular sheets for high-throughput therapeutic evaluation,” are Xixi Zhang, Robbie Cross Jr., Yujin Aha, Gillian Huskin, UAB Department of Biomedical Engineering; Will Evans, Augusta University/University of Georgia Medical Partnership, Athens, Georgia; Patrick Taejoon Hwang, Endomimetics; Jeong-a Kim, UAB Department of Medicine Division of Endocrinology and Metabolism; Hanjoong Jo, Georgia Institute of Technology and Emory University, Atlanta, Georgia; and Young-sup Yoon, School of Medicine, Emory University. Zhang is a co-first author.
Support came from National Institutes of Health grant HL163802.
“The successful private-public collaboration between Endomimetics and UAB demonstrates how UAB provides potential collaborators a great environment to research and develop innovative ideas to tackle clinically significant problems,” Jun said. “The Endomimetics team appreciates the excellent working relationship that exists among the company, the UAB School of Engineering, the Marnix E. Heersink School of Medicine, and the Bill L. Harbert Institute for Innovation and Entrepreneurship at UAB.”
At UAB, Medicine is a department in the Heersink School of Medicine, and Biomedical Engineering is a joint department in the schools of Engineering and Medicine.

In women living with HIV, preventive treatment with DHA-PPQ is a safe and effective strategy to prevent malaria during pregnancy, according to the final results of MAMAH, a clinical trial funded by the European & Developing Countries Clinical Trials Partnership (EDCTP) and coordinated by the Barcelona Institute for Global Health (ISGlobal), an institution supported by “la Caixa” Foundation. The study, published in the Lancet Infectious Diseases, could help protect the health of the estimated one million pregnant women who suffer from a double infection with malaria and HIV every year.
Pregnant women are particularly vulnerable to malaria infection. Hence the recommendation to offer preventive treatment (IPTp) based on sulphadoxine and pyrimethamine (SP) to pregnant women living in malaria-endemic areas. The problem is that these drugs are incompatible with co-trimoxazole (CTX), an antibiotic given to people with HIV to prevent bacterial infections.
“This means that the population most vulnerable to malaria infection and its consequences, namely pregnant women living with HIV, are also the least protected,” explains ISGlobal researcher Raquel González, technical coordinator of the MAMAH project, led by Clara Menéndez, director of ISGlobal’s Maternal, Child and Reproductive Health Initiative.
The aim of the project was to evaluate the safety and efficacy of two other drugs: dihydroartemisinin and piperaquine (DHA-PPQ) to prevent malaria during pregnancy in women living with HIV. The research team conducted the trial in Gabon and Mozambique with more than 600 pregnant women taking CTX in addition to antiretroviral treatment for HIV. One group of pregnant women received DHA-PPQ and the other group received a placebo.
Lower risk of malaria infection and disease
Although there was no significant difference in malaria infection at the time of delivery, women in the DHA-PPQ group had a significantly lower risk of developing clinical malaria throughout pregnancy (almost eight times lower than the placebo group) and also a lower risk (almost half) of becoming infected. DHA-PPQ was effective in women taking different antiretroviral treatments. No serious side effects were observed, and DHA-PPQ had no effect on mother-to-child transmission of HIV.
“We show that preventive treatment with DHA-PPQ is effective even in low malaria transmission settings,” says Gonzalez. “Adding this strategy to malaria control tools could significantly improve the health of thousands of mothers and their babies, especially in sub-Saharan Africa, a region where an estimated one million women living with HIV are infected with malaria during pregnancy every year,” she adds.
“We congratulate the MAMAH team on these important results in the field of malaria research, and, in particular, in providing better health to pregnant women living with HIV in malaria-endemic areas,” says Montserrat Blázquez-Domingo, EDCTP Senior Project Officer. “This study underlines the value of collaborative research that EDCTP supports and our focus on priority infectious disease affecting sub-Saharan Africa in populations often excluded from clinical trials — such as pregnant women.”
The MAMAH study is part of the EDCTP2 Programme supported by the European Union (grant number RIA2016MC-1613-MAMAH).

Published18 hours agoShareclose panelShare pageCopy linkAbout sharingThis video can not be playedTo play this video you need to enable JavaScript in your browser.By Glenn CampbellPolitical editor, BBC ScotlandIt was a beautiful day for a summer cycle through East Lothian. The sort of day where nothing could go wrong.Until it did.I was moving fast down a steep hill heading towards the village of Gifford for breakfast when I took a tumble. The road surface was broken and I clipped a rough edge and skidded. There was a split second of clarity. I could see exactly what was about to happen and that I was powerless to prevent it. The bike went one way and I went the other. I fell hard, bounced and rolled across the tarmac. I came to a halt face down on the road, too injured to move to safety. I knew the biggest danger I faced was being run over. I kept thinking: “If the next vehicle comes down the hill, the driver will struggle to see me and I will be a goner.”I was lucky. The first car on the scene came up the hill. The former police officer behind the wheel did spot me, stopped the traffic and called an ambulance. I owe him and the others who came to my aid my sincere thanks.I broke 10 ribs in this accident in June and was in the major trauma unit at the Royal Infirmary of Edinburgh for a week, where I received phenomenal care.But little did I know that these injuries would be the least of my health problems.Six weeks later, I was looking forward to getting back to work – but woke on the Saturday night clutching my left arm.It was not painful but I felt a strong burning sensation. I could not walk or talk coherently. It was as if I was drunk, although I had not had a drop of alcohol. Involuntarily, I bit down hard on my tongue and started bleeding from my mouth. At first my wife, Claire, thought I was having a stroke. It turned out I was having an epileptic fit or seizure. I had substantially recovered by the time the paramedics arrived and was making jokes as they bundled me off to hospital for checks. Within a couple of days an MRI scan revealed a tumour on the right hand side of my brain. It was pressing on the part that controls movement on the left hand side of my body. Tumours always seem to be compared in size to pieces of fruit. It is not uncommon to hear about someone having a tumour as big as a peach. Mine was much smaller. Perhaps more akin to a large grape – but no less devastating for what it represents. It’s a real shock to be told that you have a serious life-limiting condition. For about six weeks, the situation looked very bleak. The most likely scenario seemed to be that I had a glioblastoma – a fast growing cancerous tumour for which the average life expectancy after diagnosis is 12 to 18 months.I could hardly believe it. I would probably be dead before I was 50 – assuming I could safely get through surgery to remove as much of the tumour as possible. I had to move quickly to update my will and dig out my life insurance to make everything as easy as possible for my family in case the operation went wrong.The hardest thing was to tell my children Cameron, 20, and Katie, 17, what was happening to me. Getting through that without breaking down was a relief.I was surprised to discover that I am not afraid of dying. It turns out my biggest fear is FOMO – the fear of missing out. Missing out on growing old with my wife. Missing out on seeing my children complete their journeys into adulthood. Missing out on their graduations, weddings and the arrival of any children they might have. I told family and friends that I loved them and hoped for the best. The surgery was a success. My brilliant neurosurgeon at the Royal Infirmary of Edinburgh, Paul Brennan, and his team managed to get almost all of my tumour out, without damaging healthy tissue. When I came round from five hours under general anaesthetic I was euphoric – overwhelmed to be alive and feeling ridiculously well. I celebrated in the high dependency ward that night with a feast of cheese and biscuits.I recovered quickly. They operated on a Thursday and I was home walking my dog on the Saturday – a timeline I would not have imagined possible. The only way to find out exactly what they cut out was to send it for forensic examination.The pathology report took a few weeks. That was actually fairly swift – but it felt like a very long time because every day you wait for a definitive diagnosis is a real strain. When I went in to hear the results from my consultant I was prepared for the worst but hopeful for a better outcome. Once again, I was lucky. About as lucky as someone in my position can be. I do have an incurable brain cancer. It is almost certainly what will kill me, but I am optimistic that need not happen for a long time yet. I have a rare tumour called an oligodendroglioma, which tends to respond better to treatment than many other types.Over the autumn, I had 33 blasts of radiotherapy. I started chemotherapy before Christmas and I should be having the second of six chemo cocktails with my Burns supper. I have remained healthy and active throughout my treatment so far. I have been able to keep working, keep walking my dog and climb a few mountains.I am lucky to have supportive colleagues and management at BBC Scotland.I don’t want to pretend I have not experienced side effects.I found radiotherapy very tiring. Chemotherapy has made me feel nauseous and fatigued. All of this increases my risk of further seizures, which I am very keen to avoid. I manage this with medication and making plenty of time for rest. This is frustrating for someone who likes to keep busy – but the prize for good behaviour is huge.If this phase of my treatment is successful it should be possible to keep my tumour in check for some years to come. Instead of worrying about dying from brain cancer, I can see the potential for it to give me a new lease of life. In some ways that has already begun.I am spending more time with friends and family, who have humbled me with their love and support. I am taking more time to appreciate simple pleasures, especially walking in Scotland’s breathtaking landscapes. I have decided to share my story in the hope that it might offer encouragement to others. The cancer club is one that no-one wants to join but I have found its membership to be very supportive. I have drawn strength from those who have shared their experiences with me along the way. I have also started a fundraising community called Brain Power to raise money for the charity, Brain Tumour Research. It is working to establish its fifth UK research centre in Scotland – to scale up the work scientists are already doing at Edinburgh and Glasgow universities and help them progress promising new therapies into clinical trials. This is important because according to Cancer Research UK, only four in 10 of those diagnosed with a cancerous brain tumour survive for a year or more. Both Brain Tumour Research and the Brain Tumour Charity describe brain tumours as the biggest cancer killer in children and adults under the age of 40. I am for defying the odds and for trying to improve them for the brain tumour patients that come after me. Thinking back on my own case, I will never know for sure whether or not my tumour caused me to fall off my bike. I am not convinced that it did but it is still possible the crash helped reveal my tumour earlier than might otherwise have been the case. The accident has also left with me with some unfinished cycling business. When my chemotherapy is finished, I would like to get back on my bike and retrace my route through the hills of East Lothian. That could be a fitting way to celebrate the end of my cycle of cancer treatment, complete my ill-fated bike ride and finally enjoy that feast I promised myself in Gifford. Maybe I’ll have cheese and biscuits. More on this storyBBC’s Glenn Campbell treated for brain tumourPublished9 August 2023