Nevin Manimala

Nat Genet. 2025 Sep 5. doi: 10.1038/s41588-025-02326-8. Online ahead of print.

ABSTRACT

Gene expression is modulated jointly by transcriptional regulation and messenger RNA stability, yet the latter is often overlooked in studies on genetic variants. Here, leveraging metabolic labeling data (Bru/BruChase-seq) and a new computational pipeline, RNAtracker, we categorize genes as allele-specific RNA stability (asRS) or allele-specific RNA transcription events. We identify more than 5,000 asRS variants among 665 genes across a panel of 11 human cell lines. These variants directly overlap conserved microRNA target regions and allele-specific RNA-binding protein sites, illuminating mechanisms through which stability is mediated. Furthermore, we identified causal asRS variants using a massively parallel screen (MapUTR) for variants that affect post-transcriptional mRNA abundance, as well as through CRISPR prime editing approaches. Notably, asRS genes were enriched significantly among a multitude of immune-related pathways and contribute to the risk of several immune system diseases. This work highlights RNA stability as a critical, yet understudied mechanism linking genetic variation and disease.

PMID:40913182 | DOI:10.1038/s41588-025-02326-8

Surg Radiol Anat. 2025 Sep 5;47(1):199. doi: 10.1007/s00276-025-03704-x.

ABSTRACT

INTRODUCTION: Medical students primarily learn anatomy through lectures and atlases. Since mastering anatomy requires spatial visualization, dissection of cadavers has traditionally been regarded as the most effective approach in this discipline. Unfortunately, there are many drawbacks to this method, including accessibility issues. Nowadays, the use of 3D printing and other advanced technologies as educational tools in anatomy courses has been on the rise and they can play an extremely beneficial role in this regard. This study sought to evaluate the effectiveness of 3D printed anatomical models for student education.

MATERIALS & METHODS: The selected anatomical models were scanned using a 3D scanner, taking into account their 3D features and their application in hands-on learning settings. Minor modifications were made to the scanned files with the help of computer software before they were printed. Ultimately, the models were assessed by faculty members and students from different disciplines.

RESULTS: Once the models were prepared, they were given to various groups, including professors, medical students, MSc anatomy students, surgery residents, and BSc radiology students for evaluation. The opinions of these groups were then compared across two sets of models, and their assessments were analyzed in various cases. The feedback from four groups of students i.e. medical students, MSc anatomy students, surgery residents, and BSc radiology students indicated a notable contrast with the feedback from the professors’ group.

CONCLUSION: 3D printed models serve as valuable resources for teaching and learning anatomy from diverse viewpoints, catering to learners at different levels of study. Nevertheless, despite the usefulness of 3D models, anatomy professors believe that natural specimens associated with cadavers remain the most essential teaching resource for anatomy.

PMID:40913166 | DOI:10.1007/s00276-025-03704-x

Eur J Pediatr. 2025 Sep 5;184(9):601. doi: 10.1007/s00431-025-06433-w.

ABSTRACT

Long-term lead exposure damages the central nervous system, with chronic poisoning strongly linked to intellectual developmental disability (IDD) and disproportionately affecting children and adolescents. Using the Global Burden of Disease (GBD) 2021 database, this study analyzed temporal, spatial, and population-specific trends in lead-attributable IDD burden among global children/adolescents (1990-2021) and projected trends to 2040 to inform global public health strategies. GBD 2021 data characterized global, regional, and national distributions of lead-attributable IDD burden. Associations with sex, age, and Socio-Demographic Index (SDI) were evaluated via Years Lived with Disability (YLDs) and Age-Standardized YLD Rate (ASYR). Joinpoint regression quantified annual burden changes, and the Nordpred model projected 2021-2040 trends. Globally, ASYR fell from 58.088 to 38.718 per 100,000 (AAPC = -1.297%, P < 0.001), with high-SDI countries seeing a 54.0% reduction (AAPC = -2.486%) versus 32.8% in low-SDI regions. Paradoxically, low-SDI YLDs rose by 39.7%. In 2021, ASYR peaked in 15-19-year-olds at 39.906 (males) and 41.146 (females). South Asia, led by India (119.30 per 100,000), remained a high-burden hotspot. SDI correlated negatively with ASYR (ρ = -0.76, P < 0.001), with projections showing global YLDs declining to 863,352 person-years by 2040 (ASYR = 33.057).

CONCLUSION: While global progress has been made in reducing lead exposure-induced IDD, South Asia and low-SDI nations bear persistently high burdens. Strengthened international collaboration and targeted lead reduction policies are critical to advancing health equity for young people.

WHAT IS KNOWN: • Trend of the global disease burden of IDD attributed to lead exposure in the total population from 1990 to 2019.

WHAT IS NEW: • Trend of the global disease burden of IDD attributed to lead exposure in children and adolescents from 1990 to 2021, with projections up to 2040.

PMID:40913158 | DOI:10.1007/s00431-025-06433-w

Support Care Cancer. 2025 Sep 6;33(10):836. doi: 10.1007/s00520-025-09886-9.

ABSTRACT

OBJECTIVE: This study examines the effects of preoperative oral carbohydrates on the perioperative period of Fibula Free Flap surgery in oral cancer patients, aiming to enhance postoperative recovery.

METHODS: The study involved 89 patients who underwent fibula flap reconstruction surgery from January to December 2023. Patients were divided into control and experimental groups based on admission time. The control group followed standard fasting guidelines, while the experimental group received 800 mL and 200 mL of carbohydrates solution orally at 10 and 2 h pre-surgery, respectively. Data collected for both groups included comfort levels, blood glucose, surgical duration, intraoperative blood loss, fluid replacement, albumin, prealbumin, hemoglobin, PCT, IL-6, flap crisis, wound infection, bleeding, thrombosis, gastrointestinal reactions, extubation time, hospital stay, and total cost. All data were statistically analyzed.

RESULTS: The experimental group reported significantly lower thirst and hunger one hour pre-surgery (p < 0.0001) and had lower blood glucose levels one day post-surgery (p = 0.0003) compared to the control group. No significant differences were observed in other preoperative or postoperative measures.

CONCLUSIONS: Preoperative oral carbohydrates improve comfort and stabilize blood glucose levels in patients undergoing oral cancer fibula flap surgery, positively influencing perioperative management. This approach is beneficial for patients receiving this type of surgery.

PMID:40913154 | DOI:10.1007/s00520-025-09886-9

Br Dent J. 2025 Sep 5. doi: 10.1038/s41415-025-8719-y. Online ahead of print.

ABSTRACT

Purpose The aim of this study was to assess the effectiveness of a PEEK (polyether-ether-ketone) ultrasonic tip in the cleaning around implant-supported restorations and to evaluate the effect of different cement types on the amount of residual cement at the restoration margins.Materials and methods A master model with an implant analogue placed in the upper left first premolar region was used to create 72 cast models and zirconia crowns were fabricated for each model. A total of 72 zirconia crowns were divided into two main groups based on the cleaning method applied after cementation. In the first group, residual cement was cleaned using only a dental explorer, while in the second group, cleaning was enhanced by using a PEEK ultrasonic tip following the initial use of a dental explorer. Each main group was further divided into three subgroups according to the type of cement used: polycarboxylate cement, glass ionomer cement and resin cement. After cementation and cleaning, the zirconia crowns were detached from the models, and cement residue was digitally photographed from the buccal, lingual, mesial and distal surfaces. The percentage of residual cement was then evaluated using Adobe Photoshop via pixel-based digital analysis. Data were analysed using the Shapiro-Wilk test, Robust ANOVA and Bonferroni method test for multiple comparisons.Results Statistical analyses revealed a significant difference between the cleaning methods regardless of cement type (p = 0.002). The results demonstrated that cleaning with a PEEK ultrasonic tip significantly reduced residual cement compared to using a dental explorer alone. Among the tested cements, resin cement left the least residual cement, while glass ionomer and polycarboxylate cements left significantly more residue (p <0.001).Conclusions The findings emphasise the clinical advantages of the PEEK ultrasonic tip cleaning method. Additionally, resin cement demonstrated the lowest amount of residual cement.

PMID:40913142 | DOI:10.1038/s41415-025-8719-y

Br Dent J. 2025 Sep 5. doi: 10.1038/s41415-025-8716-1. Online ahead of print.

ABSTRACT

Introduction The COVID-19 pandemic significantly disrupted healthcare systems worldwide, including in Germany. This study investigated the impact of the pandemic on the management of dental abscesses and examined the implications for the upcoming German healthcare reform.Aims To assess how the COVID-19 pandemic affected hospitalisation, intensive care unit (ICU) admissions and treatment outcomes for dental abscesses, and to analyse the relationships between these findings and the German healthcare reform.Design Retrospective cohort study.Setting A major metropolitan hospital in Munich.Materials and methods In total, 200 patients (93 in 2019, 107 in 2020) with dental abscesses were studied. Data collected included demographics, pre-hospitalisation antibiotic use, ICU admissions, and length of stay (LOS). Statistical analysis compared the outcomes between the two years.Results ICU LOS significantly decreased in 2020 (3.3 days versus 13.7 days in 2019; p = 0.022). More patients in 2020 received antibiotics before hospitalisation and fewer required surgeries. Overall, hospital resource usage was more efficient in 2020.Discussion The pandemic emphasised the importance of preventive dental care. It highlighted how local dental offices can play a more significant role in managing dental emergencies, with potential implications for the German healthcare system’s future structure and resource allocation.Conclusion The COVID-19 pandemic reshaped dental emergency care and hospital resource usage. This shift has significant implications for the future organisation of healthcare, especially in the context of the German hospital reform.

PMID:40913141 | DOI:10.1038/s41415-025-8716-1

Obes Surg. 2025 Sep 6. doi: 10.1007/s11695-025-08210-y. Online ahead of print.

ABSTRACT

BACKGROUND: Bariatric surgery (BS) is the most effective treatment for severe obesity, but a significant proportion of patients experience insufficient weight loss (IWL) or weight regain. Glucagon-like peptide-1 receptor agonists (arGLP-1) have emerged as a promising adjunctive therapy for managing these suboptimal outcomes. This study evaluates the efficacy and safety of arGLP-1 in patients with IWL or WR after BS.

METHODS: A retrospective analysis was conducted on 100 patients who underwent BS (96 sleeve gastrectomy, 4 gastric bypass) and received arGLP-1 therapy (semaglutide or dulaglutide) for IWL (defined as < 50% excess weight loss (EWL) from baseline), and WR (a ≥ 10 kg increase from the nadir weight post-surgery). Data on weight loss, comorbidities, and adverse events were collected over a median follow-up of 1 year. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and chi-squared tests.

RESULTS: At 1 year, patients achieved significant weight loss with a median total weight loss (%TWL) of 25.5% and a median excess weight loss (%EWL) of 66.3% compared to 16.6% and 40.8%, respectively, at treatment initiation with BMI reduction of 3.7 kg/m². Significant improvements were observed in comorbidities, including reductions in obstructive sleep apnea (- 30%), hypertension (- 40%), and arthralgia (- 56.5%). Glycated hemoglobin levels decreased by 0.8 points. Treatment was well-tolerated, with nausea being the most common side effect (5% discontinuation rate).

CONCLUSION: arGLP-1 are effective and safe for managing IWL or WR after BS, leading to significant weight loss, comorbidity improvement, and sustained %TWL. These findings support their use as a valuable adjunctive obesity management medication (OMMs) in post-bariatric care, though long-term adherence and cost-effectiveness require further investigation.

PMID:40913138 | DOI:10.1007/s11695-025-08210-y

Eur J Appl Physiol. 2025 Sep 6. doi: 10.1007/s00421-025-05969-x. Online ahead of print.

ABSTRACT

BACKGROUND: Musculoskeletal disease (MSD), including osteoarthritis, rheumatoid arthritis, osteoporosis, and sarcopenia, poses a serious social burden. While physical activity (PA) benefits musculoskeletal health, the optimal PA level for MSD prevention remains unclear. Clarifying risk factors and biological mechanisms is essential.

METHODS: This study included 9,113 adults aged 20-60 years from NHANES 2013-2018. Blood and urine specimens were used to analyze metabolic and inflammatory markers. PA was assessed using the Global Physical Activity Questionnaire. Multivariate logistic regression, generalized additive models and mediation analysis were used to evaluate the relationships among PA, biomarkers and MSD.

RESULTS: Among 9113 participants, 2685 (29.5%) had MSD. PA levels of 600-1200 MET-min/week were associated with the greatest MSD risk reduction (24%; 95% CI 0.62-0.93) compared with inactivity after full adjustment. Participants with MSD showed higher levels of metabolic and inflammatory markers and lower PA levels (P < 0.05). Mediation analysis revealed that atherogenic index of plasma (AIP), triglycerides (TG), neutrophils (NEU), total cholesterol (TC), and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) acted as complementary mediators at the highly active PA level only, with mediation proportions of 12.4%, 7.6%, 6.1%, 6.0%, and 5.7%. While, lymphocytes (LYM) served as an indirect-only mediator across both active and highly active PA levels, accounting for 21.8% of the total effect.

CONCLUSION: In individuals aged 20-60 years, 600-1200 MET-min/week most effectively reduces MSD risk, with these associations likely mediated by metabolic and inflammatory markers. This study elucidates underlying biological mechanisms linking PA and MSD, highlighting potential metabolic and inflammatory pathways for prevention strategies.

PMID:40913129 | DOI:10.1007/s00421-025-05969-x

Eur J Hum Genet. 2025 Sep 6. doi: 10.1038/s41431-025-01929-3. Online ahead of print.

ABSTRACT

Congenital Anomalies of Kidney and Urinary Tract (CAKUT) can occur in isolation or in conjunction with one or more non-CAKUT associated congenital anomalies or neurodevelopmental disorders (CAKUT+). A molecular cause is not identified in most individuals with CAKUT+. This is due, in part, to uncertainty regarding the efficacy of genetic testing and an incomplete understanding of the genes that cause CAKUT+. Here, we use data from 515 individuals with CAKUT+ (n = 500) or isolated CAKUT (n = 15) to determine the efficacy of clinical exome sequencing (cES) and to identify new phenotype expansions that involve CAKUT. We determined that cES established a molecular diagnosis in 27.4% (141/515) of individuals in this cohort. No statistically significant difference in efficacy was seen with regards to age, sex, CAKUT phenotype, or associated organ system abnormality. Only 3.5% (5/144) to 14.6% (21/144) of the individual diagnoses made in our cohort could have been identified using one of four clinically available CAKUT gene panels. We then used a machine-learning approach to confirm that PHIP is a CAKUT gene and to implicate ADNP and SETD5 genes associated with an increased risk of CAKUT. These findings lead us to conclude that cES should be considered in individuals with CAKUT+ for whom a molecular diagnosis has not been identified, that cES has the potential to identify many diagnoses in individuals with CAKUT+ that would be missed using a CAKUT gene panel, and that individuals with ADNP-, PHIP-, and SETD5-related disorders may present with CAKUT phenotypes.

PMID:40913078 | DOI:10.1038/s41431-025-01929-3

Sci Rep. 2025 Sep 5;15(1):28716. doi: 10.1038/s41598-025-11890-2.

ABSTRACT

The processing-transportation composite robots, with their dual functions of processing and transportation, as well as comprehensive robot-machine interactions, have been widely and efficiently applied in the manufacturing industry, leading to a continuous increase in energy consumption. Hence, this work focuses on investigating robot-machine integrated energy-efficient scheduling in flexible job shop environments. To address the new problem, an innovative mixed-integer linear programming model and a novel dual-self-learning co-evolutionary algorithm are proposed, aimed at minimizing the total energy consumption and makespan. In the proposed algorithm, a three-dimensional vector is first used to comprehensively express the solution, and then a greedy decoding strategy is designed to reduce the idle time and energy consumption simultaneously. A hybrid initialization method with adaptive random selection and chaos mapping is developed to ensure the diversity and high quality of the initial solutions. A dual-self-learning mechanism, including a self-learning evolutionary mechanism and a self-learning cooperation mechanism, is designed to select suitable evolutionary operators and enhance interactions between populations, respectively. Finally, multiple sets of experiments are conducted to demonstrate the effectiveness of the proposed mathematical model, improved components and algorithm through numerical, statistical, and differential analyses.

PMID:40913072 | DOI:10.1038/s41598-025-11890-2