Metabolic dysfunction-associated steatotic liver disease, or MASLD, is a condition in which excess fat builds up in the liver and can lead to serious health problems. While abnormal lipid levels, also known as dyslipidemia, are known risk factors for MASLD, most research has focused on cholesterol and triglyceride levels measured in midlife. It is less clear whether long-term exposure to unhealthy lipid levels during young adulthood increases the risk of developing MASLD later in life.

In this study, researchers followed 2,577 participants in the Coronary Artery Risk Development in Young Adults study for 25 years. They calculated time-weighted average (TWA) lipid levels from ages 18 to 39 using up to seven repeated measurements, providing a measure of cumulative exposure over time rather than relying on a single test. At midlife, around age 50, participants underwent non-contrast abdominal CT scans to measure liver fat. The researchers also analyzed blood DNA methylation (DNAm), an epigenetic modification that can influence gene activity, at more than 840,000 sites across the genome. A total of 492 participants developed MASLD.

The results showed that higher long-term levels of triglycerides, low high-density lipoprotein (HDL) cholesterol, high non-HDL cholesterol, elevated apolipoprotein B, high low-density lipoprotein (LDL) cholesterol, and higher total cholesterol during young adulthood were all associated with a significantly increased risk of MASLD in midlife. These associations were consistent across sex, race, alcohol intake, and genetic risk groups. In addition, DNA methylation changes in the CPT1A, ABCG1, and DHCR24 genes explained between about 3 percent and 15 percent of these associations, suggesting that epigenetic mechanisms may partly link long-term lipid exposure to liver disease.

Overall, the findings show that cumulative exposure to abnormal lipid levels in young adulthood strongly predicts MASLD risk decades later, more effectively than single measurements. They also suggest that lipid-related DNA methylation changes may partially mediate this relationship, highlighting potential biological pathways and prevention targets.

Fig. 1��

Flow chart for selecting the Coronary Artery Risk Development in Young Adults study participants for analysis.

“One Paleopathology” is a new concept in the study of ancient diseases that applies the One Health approach—linking human, animal, and environmental health—to historical populations. A workshop at the University of Durham, UK, held before the 2024 International Society for Evolution, Medicine, and Public Health meeting, aimed to both define and expand this concept and encourage cross-disciplinary research and outreach. Two surveys—one immediately after the workshop and another a year later—measured both tangible outcomes, such as new research projects, and changes in participants’ understanding and use of transdisciplinary approaches.

The workshop successfully met its goals. Participants embraced the One Paleopathology framework, and eight new research projects were launched as a result. Over the following year, participants reported applying cross-disciplinary methods in their ongoing research, demonstrating a lasting impact. Overall, the workshop sparked new collaborations and research agendas and encouraged the integration of transdisciplinary thinking into long-term work, showing that it had a meaningful and sustained influence on the field.

Figure 1

The logic model used for the One Paleopathology workshop with specific goals, we were able to evaluate the outputs (direct products) as well as outcomes (the changes in attitude or knowledge that reflected the accomplishment of those goals.

Advances in imaging now allow us to study bone and dental diseases in both living patients and ancient remains. In archaeological studies, dental conditions like cavities (caries) and gum disease (periodontal disease) are common and can give clues about overall health, including risks for conditions such as heart disease. Studying mummies provides a unique window into the health of past populations and the relationship between oral and systemic health over time.

Using CT scans of Egyptian mummies, we examined dental problems, including cavities, periapical lesions (infections at the tooth root), and the distance from the tooth to the jawbone. We also looked at whether oral health problems were linked to hardened arteries. We found that severe cavities and gum disease were very common in this group. Oral health issues were associated with the number of calcified blood vessels, although age and sex also influenced these patterns.

These findings show that dental disease, including cavities and gum disease, existed in ancient populations and that poor oral health may have been connected to cardiovascular disease. Understanding these historical patterns highlights the importance of oral health across the lifespan and offers context for modern dental care, emphasizing how cultural and lifestyle factors shape oral health challenges.

Figure 1��Computed tomographic scans of Hatiay, a mummy included in the original Horus work,��with evidence of both carotid calcifications (blue arrow) and poor dental health (red arrows).

In brain imaging research, small changes in functional MRI (fMRI) signals caused by breathing and heart rate have often been dismissed as “noise.” However, these fluctuations actually contain important information about how blood vessels in the brain and the body’s autonomic functions (like heart and breathing control) work.

In this study, we used these physiological signals to examine how brain function changes with age, using data from the large Lifespan Human Connectome Project Aging study. We found that as people get older, their fMRI signals show slower responses linked to breathing, faster responses linked to the heartbeat, and stronger connections between brain and heart signals. Importantly, these changes become especially noticeable after the age of 60, suggesting that declining vascular health and changes in autonomic function play a key role in aging.

We also tested whether these fMRI patterns might be influenced by age-related changes in brain structure, blood flow, or alertness during scans. Overall, our findings highlight major age effects in fMRI signals tied to heart and breathing activity. This work shows that resting-state fMRI can be used not only to study brain connectivity but also to reveal new markers of brain physiology that could help track vascular and autonomic changes with aging.

Fig. 1: Age effects on the spatiotemporal patterns of RV-coupled fMRI dynamics.

a��The cross correlation between the global cortical fMRI signal and RV (positive lag values suggest that fMRI signals lag RV) for different age groups, with shade denoting the standard errors across subjects.��b��Intra-cortical distributions of region-specific fMRI signal lag relative to RV (based on the Schaefer 300-parcel atlas). Regions exhibiting statistically significant between-group temporal lag differences were displayed at the bottom (“Aging II > I”, FDR < 0.05).��c��Tissue-type specific temporal lags relative to RV for each age group. Error bars indicate the standard errors of RV-fMRI temporal lags across subjects, and the shaded gray area highlights ROIs that exhibited statistically significant between-group differences (FDR < 0.05). ROI labels are shown at the bottom.

]]> /valiant/2025/08/25/no-evidence-of-metabolomic-disruptions-from-real-world-intakes-of-aspartame-or-saccharin-the-coronary-artery-risk-development-in-young-adults-study/ Mon, 25 Aug 2025 19:28:26 +0000 /valiant/?p=5001 Steffen, Brian T., Lusczek, Elizabeth R., Jacobs, Prof David R., Chen, Chi, Murthy, Venkatesh L., van Horn, Linda V., Terry, James G., Carr, John Jeffrey, & Steffen, Lyn M. (2025). “.” Journal of Diabetes, 17(8), e70138.

Artificial sweeteners, like aspartame and saccharin, are common in the food supply, but there is ongoing debate about whether consuming them regularly is safe. This study looked at whether eating these sweeteners is linked to changes in blood metabolites—small molecules in the blood that indicate how the body is processing nutrients and energy.

The study included 2,160 adults, with an average age of 32 years. Researchers measured 549 different blood metabolites using advanced laboratory techniques. Participants reported their diet using a validated questionnaire, which allowed researchers to estimate how much aspartame and saccharin each person consumed. Statistical models were used to examine associations between sweetener intake and blood metabolites while accounting for other factors that could influence the results. Additional analyses were conducted to confirm the findings.

Results showed that heavy aspartame consumption (five or more servings per day) was associated with higher blood levels of saccharin, caffeine, myo-inositol, and several caffeine-related metabolites. Saccharin intake was only associated with higher blood saccharin levels. Importantly, neither aspartame nor saccharin was linked to changes in sugars, carbohydrates, fats, amino acids, or other metabolites that would suggest metabolic problems. These findings were supported by multiple sensitivity tests.

In conclusion, this is the largest study of its kind, and it found no evidence that aspartame or saccharin disrupt metabolism. However, the study cannot rule out the possibility that extremely high intakes of these sweeteners might have metabolic effects.

FIGURE 1

Volcano plots of plasma metabolites associated with intakes of (A) heavy aspartame (≥ 5 servings/day); and (B) saccharin (> 0 servings/day).

Tecovirimat is a medication approved in the U.S. and Europe to treat��mpox��(formerly called monkeypox), based on animal studies and safety tests in healthy people. However, there hasn’t been clear proof from large, controlled studies in people who actually have mpox—until now.

In this study, researchers ran a carefully controlled clinical trial in the��Democratic Republic of Congo (DRC)��to test how well tecovirimat works and how safe it is for people infected with��clade I mpox virus (MPXV), a version of the virus found in Central Africa. A total of��597 patients��with mpox were randomly given either tecovirimat or a placebo (a lookalike pill with no active medicine), and everyone received supportive care.

The main thing the researchers looked at was how long it took for skin lesions (the sores caused by mpox) to heal. They found that people taking tecovirimat recovered in about��7 days, while those taking the placebo recovered in��8 days—a very small difference that was��not statistically significant, meaning it could have happened by chance.

Other measures, like how quickly the virus disappeared from the body and how many people experienced side effects, were also similar between the two groups. About��1.7% of all patients died, which is lower than the��4.6% death ratereported for mpox in the DRC in 2023. Side effects occurred in about��71–73%��of people in both groups, and serious side effects were rare.

In this study, tecovirimat��did not significantly speed up recovery��in patients with mpox caused by the clade I virus. However, it was found to be��safe, with no major concerns about side effects. Further studies may still be needed to explore its use in different types of mpox or stages of illness.

Fig 2.

Longitudinal PCR Results According to Trial Group and Symptom Onset in the Intention-to-Treat Population.

The percentage of patients testing negative for the virus that causes mpox (MPXV) by polymerase-chain-reaction (PCR) assays of blood samples (Panel A), oropharyngeal swab specimens (Panel B), and skin-lesion specimens (Panel C) is shown according to trial group and the timing of symptom onset (≤7 days vs. >7 days before randomization). Patients with a baseline positive or negative PCR result are included. The last-observation-carried-forward method was applied to valid PCR results from baseline to 14 days after randomization. Patients who have lesion resolution are not expected to have further positive PCR results for skin-lesion specimens, so patients who had lesion resolution on or before a given time point were assumed to be negative for MPXV if no valid PCR data were available. 𝙸 bars indicate 95% confidence intervals.

Scientists study our DNA to understand genetic differences that may affect health or traits. One way to do this is by using a method called “linked-reads,” which helps piece together long stretches of DNA and find changes in the genome. However, analyzing whole genomes with linked-reads usually requires a lot of computer power, which can be a problem for large-scale studies.��

To address this, we developed a new method called RegionIndel. Instead of looking at the entire genome, RegionIndel focuses only on specific smaller sections (usually 50,000 DNA letters at a time). It uses barcodes to group DNA reads from the same region, then puts the pieces together while keeping track of which parent each piece came from. Finally, it compares the assembled sequences to a reference to find large insertions and deletions—types of genetic changes known as structural variants (SVs).��

We tested RegionIndel on a well-known human DNA sample called HG002, using two different types of linked-read data. RegionIndel found more structural variants—and did so more accurately—than several other existing methods. For example, when analyzing one type of data (called 10x linked-reads), it correctly identified about 75% of deletions and 62% of insertions. It also did a good job figuring out whether someone had 0, 1, or 2 copies of a variant, with accuracy over 80%.

�� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� �� Figure 1 ��

Schematic diagram of the RegionIndel pipeline. Input data are the high-quality reference genome and barcoded reads, each with a barcode (not shown). The reads extraction module extracts barcoded reads aligning to the region of interest. The reads with the same barcode (read cloud) form the virtual long fragment molecule. The haplotyping module partitions molecules into different parental haplotypes, and then the corresponding barcoded reads will be partitioned into different haplotypes. The local assembly module takes barcoded reads and performs de novo local assembly independently for each haplotype through SPAdes. Finally, the variant calling module integrates paftools to perform a contig-to-reference comparison to detect all variants��

The way health information is presented—especially numbers about risks and benefits—can have a big impact on how people understand and respond to it. To explore this, the Making Numbers Meaningful team reviewed over 100 studies to see how different presentation formats affect people’s reactions when comparing probabilities, like how much a treatment lowers the chance of a disease coming back. They found that people were more influenced by numbers shown as relative differences (for example, saying a treatment “cuts the risk in half”) than absolute differences (like saying it “reduces risk by 2%”). People also responded more strongly to charts that focused only on the number affected, rather than showing the full picture, and were more persuaded when messages included personal stories or information about what other people chose. Bar charts were generally preferred over icon-style graphics, especially when they included labels showing exact numbers. Overall, the review showed that the format used to present health statistics can shape how effective people think a treatment is, how much they trust the information, what choices they intend to make, and which formats they prefer. This means that clear and thoughtful presentation of numbers is essential for helping people make informed health decisions.��

Table A��

This standardized numbering system has been used for results subheadings in this article and across all Making Numbers Meaningful results articles to ensure that readers can find comparable information in all articles. Gray cells represent combinations that are not possible according to the definitions presented in Ancker et al.��

Colorectal cancer (CRC) causes over 900,000 deaths each year around the world. New research suggests that certain harmful bacteria in the colon might help promote or even cause CRC. In earlier studies, we found that a bacteria called Clostridioides difficile (C. difficile), which is commonly found in the gut of people with CRC, can speed up the development of tumors in mice. To better understand how these bacteria interact with the body during tumor growth, we used advanced techniques to study the genes and proteins in the colon. We discovered that a gene called DMBT1 behaves very differently in inflamed versus tumor-affected areas of the colon. When we looked at the gene expression in healthy colon cells exposed to C. difficile, we found that the bacteria caused DMBT1 to be more active. However, in areas where tumors were developing, this gene was almost completely turned off. We confirmed these findings with various experiments and found that DMBT1 was also turned off in tumor samples from both mice and humans. Further tests showed that a cell signaling process called WNT might be responsible for this change in the gene’s activity. Overall, our research suggests that the DMBT1 gene could be a key link between bacteria and the development of colon cancer.��

Figure 1��

Cell type identification and analysis of scRNA-seq from colonic epithelial cells in C. difficile-colonised ApcMin/+mice demonstrated unique cell states.��

(A) Schematic of experimental design: 8-week-old germ-free ApcMin/+ mice were gavaged with C. difficile-containing bacterial consortium or control consortium as previously published [], and mice were euthanized at 10 weeks. (B) Epithelial crypts were dissociated from the colonic tissue for scRNA-seq; n = 3 mice/group. Spatial transcriptomics was performed on formalin-fixed, paraffin-embedded whole colon; separate experiment with n = 3 mice/group. (C) UMAP plot with cell type assignments for clusters based on canonical mouse gene markers (supplementary material, Figure ). (D–F) UMAP plots colored by inoculation (C. difficile or control), mouse, or cell cycle phase. (G–K) UMAP plots colored by scaled gene expression (a.u. = arbitrary units) of canonical gene markers for different cell states: fetal reversion (Marcksl1), autophagy (Sqstm1), senescence (Cdkn1), intestinal plasticity (Prom1), and regenerative stemness (Anxa1).

Bhatt, Neel S.; Harris, Andrew C.; Gorfinkel, Lev; Ibanez, Katarzyna; Tkaczyk, Eric R.; Mitchell, Sandra A.; Albuquerque, Stacey; Schechter, Tal; Pavletic, Steven; Duncan, Christine N.; Rotz, Seth J.; Williams, Kirsten; Carpenter, Paul A.; Cuvelier, Geoffrey D.E. ��Transplantation and Cellular Therapy, 2025,��.��

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Chronic graft-versus-host disease (cGVHD) is a major complication that can occur after children and adolescents undergo hematopoietic cell transplantation (HCT), a treatment for certain cancers and blood disorders. However, there is limited information on how cGVHD affects long-term survival and quality of life in pediatric patients. This is an important issue since children who receive HCT have a longer life expectancy compared to adults. To address this gap in knowledge, experts in pediatric cGVHD and late effects of HCT formed a group called RESILIENT, which stands for Research and Education towards Solutions for Late effects to Innovate, Excel, and Nurture after cGVHD. The group aimed to better understand how cGVHD affects children after transplant, improve care for long-term survivors, and develop a research plan for the future.��

The task force split into four working groups, each focusing on a specific area: (1) understanding the stages of cGVHD and how it affects the ability to safely reduce or stop treatment, (2) organ damage and immune system recovery, (3) how cGVHD and its treatments impact growth and development, and (4) the psychological health of patients. These groups met in advance of a large medical conference to discuss their findings and seek feedback. The first manuscript from the group focuses on the challenges clinicians face when trying to determine when to stop or reduce the treatment for cGVHD. One major issue is distinguishing between active cGVHD (which needs treatment) and quiescent cGVHD (which is less active and might not need treatment). To address these challenges, the group recommends new ways to categorize long-term outcomes of cGVHD and offers practical guidance for clinicians on how to monitor and manage these patients over the long term, including when to adjust treatment and how to use supportive care.��

Figure 1.��The long-term goal of pediatric allogeneic HCT is to achieve not only disease eradication but also normal organ function, optimal growth and development, improve functional status, lessen symptom burden and promote high quality of life. Chronic GVHD can be a significant barrier to these goals. The RESILIENT consortium examines various aspects of chronic GVHD and long-term survivorship to achieve resilience for infants, children, and adolescents requiring allogeneic HCT.��