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Taste receptors for bitter substances are not only found on the tongue but also on cells outside the oral cavity. As a new study by the Leibniz Institute for Food Systems Biology at the Technical University of Munich now shows, extraoral bitter taste receptors could also serve as endogenous sensors for bile acids. This discovery suggests that, in addition to food components, endogenous substances may have influenced the evolution of bitter taste receptors. Furthermore, the study provides new approaches to explore the health effects of food constituents in which extraoral bitter taste receptors are involved.
As taste sensors, bitter taste receptors serve to detect and avoid potential toxins in food. Relatively recent findings also indicate that bitter taste receptors are also found on cells of the lung, brain, and gastrointestinal tract, and on blood and sperm cells. A fact that suggests further, less well-studied receptor functions in the body, especially since the human body also produces bitter substances itself.
Based on these findings, the question arises whether bitter taste receptors evolved primarily as taste receptors or rather as endogenous sensors interacting with endogenous bitter substances. The latter, of course, would require that concentrations of endogenous substances in the corresponding body fluids be sufficient to activate endogenous bitter taste receptors on extraoral tissues and cells.
Bile acids are endogenous bitter substances
Bile acids are a good example of endogenous bitter substances and are present in various body fluids. Therefore, a team led by Maik Behrens from the Leibniz Institute in Freising, Germany, investigated which of the approximately 25 human bitter taste receptor types respond to physiologically relevant bile acid concentrations. For this purpose, the team used an established cellular test system and combined functional experiments with molecular modeling approaches. The eight bile acids tested included primary, secondary, tertiary, and conjugated bile acids.
As the team shows, five bitter taste receptor types respond to the bile acids tested. “In this context, the measured activation thresholds of the receptors matched very well the bile acid concentrations reported for human body fluids in the literature,” says Florian Ziegler, a doctoral student at the Leibniz Institute who contributed significantly to the study. “Moreover, we were not only able to characterize the binding of bile acids to the bitter taste receptor TAS2R1 by modeling studies but even reproduced the differences of experimental activity data,” adds Antonella Di Pizio, who heads the Molecular Modeling group at the Leibniz Institute.
Bile acids activate extraoral bitter taste receptors
“Our results suggest that there is indeed a physiological relationship between bile acids and certain extraoral bitter taste receptors and that the latter act as endogenous sensors of bile acid levels. They also support the hypothesis that not only external factors such as bitter food constituents have influenced the evolution of bitter taste receptors, but also endogenous ones,” summarizes principal investigator Maik Behrens. However, further studies are urgently needed to clarify the exact biological functions of the extraoral receptors, the biologist continues. He adds: “Gaining a deeper understanding of these functions could provide valuable insights into the potential health effects of food components when they interact with the extraoral bitter taste receptor ligand systems.”

A new study by investigators from the Institute for Health Metrics and Evaluation (IHME) at the University of Washington and Mass General Brigham found that maternal mortality rates have worsened from 1999 to 2019, hitting some racial and ethnic groups and states harder than others. Their results are published in the Journal of the American Medical Association (JAMA).
“Maternal mortality is a crisis in the United States. These rates have been increasing over the past several decades and were exacerbated by the pandemic,” said co-first author Allison Bryant, MD, MPH, senior medical director for health equity at Mass General Brigham. “Our study sheds light on the wide disparities within maternal mortality rates — the specter of maternal death differentially burdens some ethnic and racial populations.”
Maternal mortality, or maternal death, is a death during or up to one year after the end of pregnancy. According to the Centers for Disease Control and Prevention, common causes of maternal death include mental health conditions — including death by suicide, and overdose related to substance use disorder — excessive bleeding (hemorrhage), cardiac and coronary conditions, infection, thromboembolism (blood clot), cardiomyopathy (a disease of the heart muscle) and hypertensive disorders of pregnancy (relating to high blood pressure). Previous research has found that rates of different causes of maternal mortality vary by race and ethnicity.
Bryant and co-authors used the National Vital Statistics System data on deaths and live births in each state and racial/ethnic group between 1999 and 2019. They then used a modeling process to create estimates of maternal deaths over those periods. This modeling estimated maternal mortality for each state and each race and ethnicity out of every 100,000 live births without potentially breaching any person’s privacy.
“These disparities in maternal mortality are just the tip of the iceberg and tell us a lot about the health risks facing people in the states where these deaths are most likely to occur, ” said Greg Roth, associate professor in the Division of Cardiology and Director of the Program in Cardiovascular Health Metrics at IHME. “In the U.S., maternal deaths are often caused by vascular diseases like severe high blood pressure or blood clots. So maternal deaths share many of the same drivers as heart attacks, strokes, and heart failure. Our state-by-state research emphasizes where we need to focus our prevention efforts and which groups are suffering the most.”
For all ethnic and racial groups, maternal mortality more than doubled over this time period. These rates have been rising most substantially for American Indian and Alaskan Native people. The maternal mortality rates for Black women were the highest of any group, but the average of state-level rates had started to plateau around 2015 (pre-COVID) for Black women. Factors like structural racism and interpersonal racism play into these disparities, Bryant said. Substantial prevention and awareness efforts around maternal mortality may have had an impact for some populations, but not all.
Maternal mortality rates and disparities varied widely across states. The South had high maternal mortality across all race and ethnicity groups, but especially for Black individuals. Black individuals had the highest maternal mortality rates in some states in the Northeast, which tripled over the time of the study. Maternal mortality rates in the Midwest and the Great Plains states were where highest rates were found for American Indian and Alaskan Native women.
“Often, states in the South are called out as having the worst maternal mortality rates in the nation, whereas California and Massachusetts have the best. But that doesn’t tell the whole story,” Bryant said. “It’s essential to look at the disparities between populations that exist even in the ‘best’ states.”
The study had several limitations. The researchers didn’t always have access to information about the causes of maternal death. And the way maternal deaths are recorded on death certificates has changed in the U.S. over the time of this study.
The data used in the study stopped prior to the pandemic in 2019. National data show maternal mortality increased in 2020 and 2021 when it was harder to access health care. The pandemic also hindered some prevention efforts to decrease the deaths of Black women. The pandemic may have widened the disparities seen in this study, Bryant said.
“Our findings provide important insights on maternal mortality rates leading up to the pandemic, and it’s likely that we’ll see a continued increase in the risk of maternal mortality across all populations if we analyze data from subsequent years,” Bryant said. “Black individuals would likely still have the highest rate, but there may be a higher uptick in some of the other groups in the last few years. As we emerge from the pandemic, we must renew our focus on addressing maternal mortality.”
This study was supported in part by grants from the National Heart, Lung, and Blood Institute (R01HL136868), the National Institutes of Health (75N94019C00016), and Gates Ventures LLC.

Artificial intelligence can predict on- and off-target activity of CRISPR tools that target RNA instead of DNA, according to new research published in Nature Biotechnology.
The study by researchers at New York University, Columbia Engineering, and the New York Genome Center, combines a deep learning model with CRISPR screens to control the expression of human genes in different ways — such as flicking a light switch to shut them off completely or by using a dimmer knob to partially turn down their activity. These precise gene controls could be used to develop new CRISPR-based therapies.
CRISPR is a gene editing technology with many uses in biomedicine and beyond, from treating sickle cell anemia to engineering tastier mustard greens. It often works by targeting DNA using an enzyme called Cas9. In recent years, scientists discovered another type of CRISPR that instead targets RNA using an enzyme called Cas13.
RNA-targeting CRISPRs can be used in a wide range of applications, including RNA editing, knocking down RNA to block expression of a particular gene, and high-throughput screening to determine promising drug candidates. Researchers at NYU and the New York Genome Center created a platform for RNA-targeting CRISPR screens using Cas13 to better understand RNA regulation and to identify the function of non-coding RNAs. Because RNA is the main genetic material in viruses including SARS-CoV-2 and flu, RNA-targeting CRISPRs also hold promise for developing new methods to prevent or treat viral infections. Also, in human cells, when a gene is expressed, one of the first steps is the creation of RNA from the DNA in the genome.
A key goal of the study is to maximize the activity of RNA-targeting CRISPRs on the intended target RNA and minimize activity on other RNAs which could have detrimental side effects for the cell. Off-target activity includes both mismatches between the guide and target RNA as well as insertion and deletion mutations. Earlier studies of RNA-targeting CRISPRs focused only on on-target activity and mismatches; predicting off-target activity, particularly insertion and deletion mutations, has not been well-studied. In human populations, about one in five mutations are insertions or deletions, so these are important types of potential off-targets to consider for CRISPR design.
“Similar to DNA-targeting CRISPRs such as Cas9, we anticipate that RNA-targeting CRISPRs such as Cas13 will have an outsized impact in molecular biology and biomedical applications in the coming years,” said Neville Sanjana, associate professor of biology at NYU, associate professor of neuroscience and physiology at NYU Grossman School of Medicine, a core faculty member at New York Genome Center, and the study’s co-senior author. “Accurate guide prediction and off-target identification will be of immense value for this newly developing field and therapeutics.”
In their study in Nature Biotechnology, Sanjana and his colleagues performed a series of pooled RNA-targeting CRISPR screens in human cells. They measured the activity of 200,000 guide RNAs targeting essential genes in human cells, including both “perfect match” guide RNAs and off-target mismatches, insertions, and deletions.

Sanjana’s lab teamed up with the lab of machine learning expert David Knowles to engineer a deep learning model they named TIGER (Targeted Inhibition of Gene Expression via guide RNA design) that was trained on the data from the CRISPR screens. Comparing the predictions generated by the deep learning model and laboratory tests in human cells, TIGER was able to predict both on-target and off-target activity, outperforming previous models developed for Cas13 on-target guide design and providing the first tool for predicting off-target activity of RNA-targeting CRISPRs.
“Machine learning and deep learning are showing their strength in genomics because they can take advantage of the huge datasets that can now be generated by modern high-throughput experiments. Importantly, we were also able to use “interpretable machine learning” to understand why the model predicts that a specific guide will work well,” said Knowles, assistant professor of computer science and systems biology at Columbia Engineering, a core faculty member at New York Genome Center, and the study’s co-senior author.
“Our earlier research demonstrated how to design Cas13 guides that can knock down a particular RNA. With TIGER, we can now design Cas13 guides that strike a balance between on-target knockdown and avoiding off-target activity,” said Hans-Hermann (Harm) Wessels, the study’s co-first author and a senior scientist at the New York Genome Center, who was previously a postdoctoral fellow in Sanjana’s laboratory.
The researchers also demonstrated that TIGER’s off-target predictions can be used to precisely modulate gene dosage — the amount of a particular gene that is expressed — by enabling partial inhibition of gene expression in cells with mismatch guides. This may be useful for diseases in which there are too many copies of a gene, such as Down syndrome, certain forms of schizophrenia, Charcot-Marie-Tooth disease (a hereditary nerve disorder), or in cancers where aberrant gene expression can lead to uncontrolled tumor growth.
“Our deep learning model can tell us not only how to design a guide RNA that knocks down a transcript completely, but can also ‘tune’ it — for instance, having it produce only 70% of the transcript of a specific gene,” said Andrew Stirn, a PhD student at Columbia Engineering and the New York Genome Center, and the study’s co-first author.
By combining artificial intelligence with an RNA-targeting CRISPR screen, the researchers envision that TIGER’s predictions will help avoid undesired off-target CRISPR activity and further spur development of a new generation of RNA-targeting therapies.
“As we collect larger datasets from CRISPR screens, the opportunities to apply sophisticated machine learning models are growing rapidly. We are lucky to have David’s lab next door to ours to facilitate this wonderful, cross-disciplinary collaboration. And, with TIGER, we can predict off-targets and precisely modulate gene dosage which enables many exciting new applications for RNA-targeting CRISPRs for biomedicine,” said Sanjana.
Additional study authors include Alejandro Méndez-Mancilla and Sydney K. Hart of NYU and the New York Genome Center, and Eric J. Kim of Columbia University. The research was supported by grants from the National Institutes of Health (DP2HG010099, R01CA218668, R01GM138635), DARPA (D18AP00053), the Cancer Research Institute, and the Simons Foundation for Autism Research Initiative.

Gene therapy that alters hemoglobin genes may be an answer to curing sickle cell disease (SCD) and beta thalassemia. These two common life-threatening anemias afflict millions of individuals across the globe. Scientists at St. Jude Children’s Research Hospital and the Broad Institute of MIT and Harvard used a next-generation genome editing technology, adenosine base editing, to restart fetal hemoglobin expression in SCD patient cells. The approach raised the expression of fetal hemoglobin to higher, more stable, and more uniform levels than other genome editing technologies that use CRISPR/Cas9 nuclease in human hematopoietic stem cells. The findings were published today in Nature Genetics.
SCD and beta thalassemia are blood disorders affecting millions of people; mutations in the gene that encodes an adult version of the oxygen-carrying molecule hemoglobin cause these disorders. Restoring gene expression of an alternative hemoglobin subunit active in a developing fetus has previously shown therapeutic benefit in SCD and beta thalassemia patients. The researchers wanted to find and optimize genomic technology to edit the fetal hemoglobin gene. One alteration installed by adenosine base editing was particularly potent for restoring fetal hemoglobin expression in post-natal red blood cells.
“We showed base editors meaningfully increase fetal hemoglobin levels,” said lead corresponding author Jonathan Yen, Ph.D., St. Jude Therapeutic Genome Engineering group director. “Now, my Therapeutic Genome Engineering team is already hard at work, starting to optimize base editing to move this technology to the clinic.”
Hemoglobin holds the key
Adult hemoglobin, expressed primarily after birth, contains four protein subunits — two beta-globin and two alpha-globin. Mutations in the beta-globin gene cause sickle cell disease and beta-thalassemia. But humans have another hemoglobin subunit gene (gamma-globin), which is expressed during fetal development instead of beta-globin. Gamma-globin combines with alpha-globin to form fetal hemoglobin. Normally around birth, gamma-globin expression is turned off, and beta-globin is turned on, switching from fetal to adult hemoglobin. Genome editing technologies can introduce mutations that turn the gamma-globin gene back on, thereby increasing fetal hemoglobin production, which can effectively substitute for defective adult hemoglobin production.
“We used a based editor to create a new TAL1 transcription factor binding site that causes particularly strong induction of fetal hemoglobin,” Yen said. “Creating a new transcription factor binding site requires a precise base pair change — something that can’t be done using CRISPR-Cas9 without generating unwanted byproducts and other potential consequences from double-stranded breaks.”
“The gamma-globin [fetal hemoglobin] gene is a good target for base editing because there are very precise mutations that can reactivate its expression to induce expression after birth, which may provide a powerful ‘one-size-fits-all’ treatment for all mutations that cause SCD and beta-thalassemia,” said co-corresponding author Mitchell Weiss, M.D., Ph.D., St. Jude Department of Hematology chair.

Thus, scientists want to restore fetal hemoglobin expression because it is a more universal treatment for major hemoglobin disorders than correcting the SCD mutation or hundreds of mutations that cause beta thalassemia. Increasing fetal hemoglobin expression has the potential to therapeutically benefit most patients with SCD or beta thalassemia, regardless of their causative mutations. Researchers have previously shown proof-of-principle with multiple genome editing approaches, but this study is the first to systematically compare these different strategies’ efficacy.
“We looked closely at the individual DNA sequence outcomes of nucleases and base editors used to make therapeutic edits of fetal hemoglobin genes. Since nucleases often generate complex, uncontrolled mixtures of many different DNA sequence outcomes, we characterized how each nuclease-edited sequence affects fetal hemoglobin expression. Then we did the same for base editing outcomes, which were much more homogeneous,”said co-corresponding author David Liu, Ph.D., Richard Merkin, Professor at Broad Institute of MIT and Harvard, whose lab invented base editing in 2016.
The study discovered that using base editing at the most potent site in the gamma-globin promoter achieved 2- to 4-fold greater HbF levels than Cas9 editing. They further demonstrated that these base edits could be retained in engrafting blood stem cells from healthy donors and SCD patients by putting them into immunocompromised mice.
Addressing safety concerns
“Ultimately, we showed that not all genetic approaches are equal,” Yen said. “Base editors may be able to create more potent and precise edits than other technologies. But we must do more safety testing and optimization.”
When compared for safety, base editing caused fewer genotoxic events, such as p53 activation and large deletions. Base editing was much more consistent in its edits and products — a highly desirable safety property for a clinical therapy. In contrast to conventional Cas9, which generates uncontrolled mixtures of insertion and deletion mutations termed “indels,” base editing generates precise nucleotide changes with few undesired byproducts.

“In our comparison, we found unanticipated problems with conventional Cas9 nucleases,” Weiss said. “We were somewhat surprised that not every Cas9 insertion or deletion raised fetal hemoglobin to the same extent, indicating the potential for heterogeneous biological outcomes with that technology.” The group found that individual red blood cells derived from hematopoietic stem cells treated with the same Cas9 produce a more variable amount of fetal hemoglobin compared to cells treated with base editing. Thus, base editing produced more potent, reliable, and consistent outcomes, which are desirable therapeutic properties.
Though base editing performed well, researchers have yet to determine its safety in patients. Notably, base editing may have some risks not presented by Cas9; for example, some early base editors can cause undesired changes in genomic DNA or RNA at off-target sites. The group showed that these changes are relatively small and not predicted to be harmful, but deeper studies are warranted to evaluate these risks fully.
The future of gene editing therapeutics
Throughout the study, the scientists directly compared the performance of Cas9 nucleases at two different target sites that induce fetal hemoglobin production in different ways and base editing. Base editing uses a distinct editing mechanism that directly converts one DNA base pair to another, rather than cutting the DNA double helix into two pieces.
The Cas9 nuclease approaches create mixtures of deletions and insertions that impair the expression or activity of BCL11A, a well-known gamma-globin gene repressor. In contrast, base editing creates a novel transcription factor binding motif within the gamma-globin promoter. The Cas9 nuclease approaches and a different base editing approach are being tested through clinical trials. St. Jude is participating in some of these studies.
“It is very important to test and compare different genome editing approaches for treating SCD and beta-thalassemia because the best ones are not known,” said Weiss.
John Tisdale, M.D., a study co-author and the Cellular and Molecular Therapeutics Branch chief at the National Heart, Lung, and Blood Institute, agreed. “The science of gene editing is moving quickly, and we are now able to envision multiple different strategies for combating sickle cell disease,” Tisdale said. “These findings bring us a step closer to our goal of broadly available cures.”

“Large Language Models are neural network language models with remarkable conversational skills. They generate human-like responses and engage in interactive conversations. However, they often generate highly convincing statements that are verifiably wrong or provide inappropriate responses. Today there is no way to be certain about the quality, evidence level, or consistency of clinical information or supporting evidence for any response. These chatbots are unsafe tools when it comes to medical advice and it is necessary to develop new frameworks that ensure patient safety,” said Prof. Stephen Gilbert, Professor for Medical Device Regulatory Science at Else Kröner Fresenius Center for Digital Health at TU Dresden.
Challenges in the regulatory approval of large language models
Most people research their symptoms online before seeking medical advice. Search engines play a role in decision-making process. The forthcoming integration of LLM-chatbots into search engines may increase users’ confidence in the answers given by a chatbot that mimics conversation. It has been demonstrated that LLMs can provide profoundly dangerous information when prompted with medical questions.
LLM’s underlying approach has no model of medical “ground truth,” which is inherently dangerous. Chat interfaced LLMs have already provided harmful medical responses and have already been used unethically in ‘experiments’ on patients without consent. Almost every medical LLM use case requires regulatory control in the EU and US. In the US their lack of explainability disqualifies them from being ‘non devices’. LLMs with explainability, low bias, predictability, correctness, and verifiable outputs do not currently exist and they are not exempted from current (or future) governance approaches.
In this paper the authors describe the limited scenarios in which LLMs could find application under current frameworks, they describe how developers can seek to create LLM-based tools that could be approved as medical devices, and they explore the development of new frameworks that preserve patient safety. “Current LLM-chatbots do not meet key principles for AI in healthcare, like bias control, explainability, systems of oversight, validation and transparency. To earn their place in medical armamentarium, chatbots must be designed for better accuracy, with safety and clinical efficacy demonstrated and approved by regulators,” concludes Prof. Gilbert.

The Health Insurance Review & Assessment Service revealed that over the last year, more than 370,000 Koreans sought medical help for infertility or difficulties in conceiving. This represents a 4.7 percent increase in infertility-related treatments and a 16 percent rise in subfertility-related treatments compared to the 2018 data. Korea’s birth rate may be declining, but an increasing number of people are seeking medical attention for these issues. These conditions may stem from numerous factors, so an accurate determination of the cause is crucial. Both the individual’s gender and the nature of the problem must be taken into account before deciding on the appropriate treatment.
A healthy endometrium plays a pivotal role in successful pregnancies. A thin endometrium reduces the likelihood of effective embryo implantation, with a high chance of subsequent miscarriage — a significant contributing factor to female infertility. Current treatment approaches, such as hormone therapy and endometrial injections, have shown limited success. A joint research team from Pohang University of Science and Technology (POSTECH, President Moo Hwan Kim) and CHA University, took one step closer to personalized treatment by developing a gel that mimics the environment of uterine cells, inducing endometrial regeneration and elucidating its mechanism.
The team, led by Professor Dong-Woo Cho from Department of Mechanical Engineering, Professor Jinah Jang from the Department of Mechanical Engineering and the Department of Convergence IT Engineering, PhD student Tugce Sen from the Department of Mechanical Engineering at POSTECH in collaboration with Professor Youn-Jung Kang and Dr. Jungho Ahn from the Department of Biochemistry at the School of Medicine and PhD student Danbi Lee from the Department of Biomedical Science at the School of Life Science, CHA University, developed a hydrogel using a uterus-derived decellularized extracellular matrix (UdECM). Their study demonstrated that this hydrogel could regenerate the endometrium, and for the first time, revealed the mechanism controlling this process. The research has been published in Advanced Functional Materials.
Decellularized extracellular matrices (dECMs) are assemblies of biomolecules, with cellular components such as the nucleus and cell membranes removed. These matrices closely resemble the in vivo environment, so they are used in regeneration and transplantation of tissue and organs such as the heart and kidneys. They are also employed in tissue fabrication through 3D printing.
The team developed a hydrogel based on UdECMs, with characteristics from two different tissues: the entire uterine tissue and a specific layer of the endometrium. The protein composition of the hydrogel closely resembled the actual endometrial components and was tested in animal models to verify its effectiveness. When injected, the hydrogel was found to induce the recovery of the endometrial thickness in mice, creating a favorable environment for embryo implantation. As a biomaterial, the hydrogel has low cytotoxicity, ensuring a 90% survival rate of implanted embryos.
The research team further discovered the involvement of insulin-like growth factor (IGF1) and insulin growth factor-binding protein (IGFBP3) in endometrial regeneration. This discovery provides a platform for research on endometrial regeneration going forward. In addition, depending on the tissue from which the hydrogel is made, such as the endometrium and muscles, the team confirmed therapeutic effects against various conditions such as intrauterine adhesions and repeated implantation failures. This opens the way for personalized treatments based on the state of the patient’s endometrium.
Professor Dong-Woo Cho, who led the research, is optimistic about their research potential, stating “We have successfully developed a uterine tissue-specific hydrogel for endometrial regeneration and successful pregnancy. I am hopeful that further research into its clinical application can bring hope to patients grappling with infertility.”
This research was conducted with the support of the Mid-Career Research Program of the National Research Foundation of Korea and the Korean Fund for Regenerative Medicine funded by the Ministry of Science and ICT and the Ministry of Health and Welfare.

Pregnant women may be better supported by trained dietitians to control weight gain during pregnancy, a new analysis of almost 100 studies shows.
The meta-analysis of almost 35,000 participants across 99 studies published in JAMA Network Open found that interventions from allied health professionals such as dietitians were the most beneficial for controlling gestational weight gain (GWG).
Spanning 30 years of international evidence, the research team including maternal health expert Professor Shakila Thangaratinam from the University of Birmingham identified that between 6 and 20 sessions on a one-to-one basis were most effective. Those sessions need to consider practical elements of pregnancy including nausea which may affect food and vegetable consumption, as well as cravings and fatigue.
The team also found less evidence for the exercise component of weight management during pregnancy and plans to manage weight gain that include exercise need to be carried out over a longer period of time over 20 weeks.
Professor Shakila Thangaratinam, Dame Hilda Lloyd Chair of Maternal and Perinatal Health at the University of Birmingham and co-author of the paper said:
“Weight gain during pregnancy is a normal process but the old adage that expectant mums are ‘eating for two’ and don’t need to worry about weight gain can lead to health consequences for mum and baby. We know that excessive gestational weight gain increasing the risks of the development diabetes and other complications.
“This study set about to encapsulate 30 years of evidence on what works well and not, and we found that experts in their fields such as dietitians were most effective at supporting healthy weight gain. Other interventions were also found to have some success but need to be started soon into the journey of pregnancy.”
Cheryce L. Harrison, BBNSc, PhD, senior research fellow and co-lead of the Healthy Lifestyle Stream at the Monash Centre for Health Research and Implementation at the School of Public Health and Preventive Medicine, Monash University in Melbourne, Australia, and colleagues said:
“In a secondary analysis of our 2022 systematic review reporting on the association of lifestyle interventions with efficacy in optimizing gestational weight gain, this meta-analysis aims to elucidate and describe components of antenatal lifestyle interventions that are associated with optimized gestational weight gain within published randomized clinical trials, providing critical and pragmatic information for implementations of trials in antenatal care settings.”

A group led by researchers at Nagoya University in Japan has developed a technology to capture and release cell-free DNA (cfDNA) on nanowire surfaces from urine. By extracting this DNA, they were able to successfully detect IDH1 mutation, a characteristic genetic mutation of gliomas, a type of brain tumor. Their findings increase the effectiveness of cancer detection tests using urine. They published their results in the journal Biosensors and Bioelectronics.
Brain tumors are often examined only after the appearance of symptoms, such as paralysis of the limbs. But even when they are detected, they are often so advanced that it is difficult to remove them by surgery. Among these tumors, some of the deadliest are gliomas. These tumors have an average survival time as low as 12-18 months. Therefore, for the patient to have a chance of survival, early detection is necessary.
As many patients have routine physicals in which they give urine samples, these samples could be effectively used to look for evidence of brain tumors. One characteristic of brain tumors is the presence of cfDNA, which are small DNA particles released as the tumor rejuvenates its cells and disposes of old damaged ones. Usually, the host’s cfDNA is cleared up by macrophages, but in the case of cancer cells, the cells divide so quickly that there is excess leftover cfDNA, which is excreted in the urine.
“The detection of these cells as a non-invasive way to check for cancer has been approved by the U.S. Food and Drug Administration for cancer screening, diagnosis, prognosis, and monitoring of cancer progression and treatment response,” Professor Takao Yasui, a member of the research group, said. “However, a major bottleneck is the lack of techniques to isolate cfDNA efficiently from urine, as the excreted cfDNA may be short, fragmented, and low concentration.”
To overcome this problem, a team consisting of Professor Takao Yasui, Professor Yoshinobu Baba, and Researcher Hiromi Takahashi from the Graduate School of Engineering, along with Professor Atsushi Natsume from the Institutes of Innovation for Future Society, Nagoya University, in collaboration with Professor Takeshi Yanagida from the University of Tokyo, and Associate Professor Sakon Rahong from King Mongkut’s Institute of Technology Ladkrabang, Thailand, used a catch-and-release method on zinc oxide (ZnO) nanowire surfaces to capture cfDNA and extracellular vesicles from gliomas.
ZnO was chosen because water molecules adsorb on the surface of ZnO nanowires. These water molecules then form hydrogen bonds with any cfDNA in the urine sample. The bonded cfDNA can then be washed out, allowing researchers to isolate trace amounts of it in a sample.
Their technique was a resounding success. “We succeeded in isolating urinary cfDNA, which was exceptionally difficult with conventional methods,” Yasui said. “Although in a previous experiment, we showed that our nanowire could capture cancer extracellular vesicles, which we found in this sample too; the surprising thing was the capture of cfDNA using a similar technique. When we extracted the cfDNA, we detected the IDH1 mutation, which is a characteristic genetic mutation found in gliomas. This was exciting for us, as this is the first report of the detection of the IDH1 mutation from a urine sample as small as 0.5 ml.”
“This research overcomes the shortcomings of currently used methods by using chemical, biological, medical and nanotechnological techniques to provide a state-of-the-art method for the clinical use of urinary cfDNA, especially as an analytical tool to facilitate the early diagnosis of cancer.” Yasui said. “Although we tested gliomas, this method opens new possibilities for the detection of tumor mutations. If we know the type of mutation to look for, we can easily apply our technique to detect other types of tumors, especially the detection of those that cannot be isolated by conventional methods.”

Published22 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesSmartwatches might help diagnose Parkinson’s disease up to seven years ahead of symptoms, a study suggests.The UK Dementia Research Institute team at Cardiff University used artificial intelligence to analyse data from 103,712 smartwatch wearers.And by tracking their speed of movement over a single week, between 2013 and 2016, they were able to predict which would go on to develop Parkinson’s.It is hoped this could ultimately be used as a screening tool.But more studies, comparing these findings with other data gathered around the world, are needed to check how accurate it will be, the researchers say, in the journal Nature Medicine. The brains of people with Parkinson’s disease become damaged over many years.Symptoms include:involuntary shaking or tremorsslow movement stiff and inflexible musclesBut often by the time a diagnosis has been made, there has already been too much irreversible damage to brain cells. And since about 30% of the UK population wore smartwatches, study leader Dr Cynthia Sandor said, they might offer a cheap and reliable way to identify early-stage Parkinson’s.”We have shown here that a single week of data captured can predict events up to seven years in the future,” she said.”With these results, we could develop a valuable screening tool to aid in the early detection of Parkinson’s. “This has implications both for research, in improving recruitment into clinical trials, and in clinical practice, in allowing patients to access treatments at an earlier stage, in future, when such treatments become available.”The study used data from the UK Biobank, an in-depth health database of more than half a million people.Parkinson’s disease device trialled at hospitalResearch could reveal early causes of Parkinson’sDementia risk higher for footballers than keepersDr Kathryn Peall, who worked on the study, told BBC News it appeared to be accurate and distinguish Parkinson’s from other things that might affect movement, such as old age or frailty.”We compared our model across a number of different disorders, including other types of neurodegenerative disorders, individuals with osteoarthritis, and other movement disorders, amongst others, an advantage of being able to work with a dataset such as the UK Biobank,” she said.”The results from individuals diagnosed with Parkinson’s disease were distinct.”But whether people should be told they had Parkinson’s, years before symptoms developed, “will always remain an individual and personal choice”.”Where this work is potentially important to the field is that we ultimately hope that new therapies that allow us to slow disease progression will become available,” Dr Peall added.More on this storyParkinson’s disease device trialled at hospitalPublished11 AprilResearch could reveal early causes of Parkinson’sPublished11 MayDementia risk higher for footballers than keepersPublished17 March

Published2 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Hannah DugdaleBy Andy GiddingsBBC News, West MidlandsAn appeal for a million pounds has been launched to pay for leukaemia treatment for a 20-month-old girl.Hallie, from Coventry, was diagnosed at Birmingham Children’s Hospital when she was eight months old.But when her last stem cell transplant failed to work, her family said they were told their best option might be to pay for treatment in the United States.”It seems a very big mountain to climb,” Hallie’s aunt, Hannah Dugdale, said.Hallie was first diagnosed in the summer of 2022 while on a family holiday in Spain and was flown home for treatment.She has a rare form of leukaemia known as JMML and has undergone chemotherapy, blood transfusions and two stem cell transplants.Ms Dugdale said they discovered on Thursday the latest transplant had not worked and a consultant at the Birmingham hospital suggested their only remaining option was CAR T-cell therapy.Image source, Hannah DugdaleCAR-T works by removing a type of immune system cell, called a T cell, from the patient’s blood.Those cells are then genetically modified in the lab to make them more effective at targeting cancer cells, multiplied, and infused back into the patient drop by drop.A trial is due to start at Great Ormond Street Hospital in the coming months but Hallie’s aunt said they would prefer not to wait that long and were hoping to take her to America instead.It will require a third transplant, which the family said the NHS will not fund.Ms Dugdale said she and her sister had talked about having children for a long time and said Hallie is “the sweetest little girl, she’s is so gentle and kind-natured”.Her niece “deserves to be given every chance at a long and happy life”, she added.She said her sister, Kim, was “devastated as any mother would be” but also overwhelmed by the support she received and the appeal had already passed £180,000.Ms Dugdale said she hoped they would be able to start the treatment before they raised the full amount.Birmingham Children’s Hospital and NHS England have been contacted for a response.Follow BBC West Midlands on Facebook, Twitter and Instagram. Send your story ideas to: newsonline.westmidlands@bbc.co.ukMore on this story’Umbilical cord blood transplant saved my daughter’Published20 JuneDonor needed for four-year-old girl with leukaemiaPublished25 AprilFriends rally round to help mum with cancerPublished1 July 2022’I was very lucky to get trial cancer therapy’Published7 January 2022More than £1m raised for baby’s cancer treatmentPublished29 March 2021Related Internet LinksBirmingham Children’s HospitalThe BBC is not responsible for the content of external sites.