Single-nucleus multiomic analysis of Beckwith-Wiedemann syndrome liver reveals PPARA signaling enrichment and metabolic dysfunction.

Beckwith-Wiedemann Syndrome (BWS) is an epigenetic overgrowth syndrome caused by methylation changes in the human 11p15 chromosomal locus. Patients with BWS exhibit tissue overgrowth, as well as an increased risk of childhood neoplasms in the liver and kidney. To understand the impact of these 11p15 changes, specifically in the liver, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) to generate paired, cell-type-specific transcriptional and chromatin accessibility profiles of both BWS-liver and nonBWS-liver nontumorous tissue. Our integrated RNA+ATACseq multiomic approach uncovered hepatocyte-specific enrichment and activation of the peroxisome proliferator-activated receptor α (PPARA) - a liver metabolic regulator. To confirm our findings, we utilized a BWS-induced pluripotent stem cell (iPSC) model, where cells were differentiated into hepatocytes. Our data demonstrates the dysregulation of lipid metabolism in BWS-liver, which coincided with observed upregulation of PPARA during hepatocyte differentiation. BWS liver cells exhibited decreased neutral lipids and increased fatty acid ß-oxidation, relative to controls. We also observed increased reactive oxygen species (ROS) byproducts in the form of peroxidated lipids in BWS hepatocytes, which coincided with increased oxidative DNA damage. This study proposes a putative mechanism for overgrowth and cancer predisposition in BWS liver due to perturbed metabolism.

Tracing the Scientific Legacy: Bibliometric Analysis of LATAM Research in Bariatric Surgery for 33 Years.

INTRODUCTION: Metabolic and bariatric surgery (MBS) has experienced considerable growth, addressing the challenges of obesity and its complications. The lack of a comprehensive bibliometric analysis in Latin America motivates this study, highlighting the need to understand the evolution of research in this area and its impact on clinical decision-making and health policies. METHODOLOGY: A cross-sectional bibliometric study was carried out using the Scopus database. A structured search strategy was designed to identify articles related to bariatric surgery with authors affiliated with Latin American countries. Inclusion and exclusion criteria were applied, followed by a descriptive and bibliometric analysis of the scientific production found. RESULTS: A total of 3553 documents published between 1991 and 2024 were included. There was an annual growth of 11%, with an average age of documents of 7.5 years. A concentration was observed in some countries, notably Brazil, Mexico, and Chile. Although scientific output increased, the average number of citations per article showed a downward trend since 2003. DISCUSSION: Despite the growth in scientific production, the quality and relevance of research is questioned, especially given the decrease in the impact received. It highlights the lack of meaningful regional collaboration, which could limit the sharing of knowledge and resources. Questions are raised about gaps in research capacity and the economic and development implications are discussed. CONCLUSIONS: This study provides valuable information to strengthen future research in bariatric surgery in Latin America. It highlights the importance of promoting regional and international collaboration and improving research training in countries with less participation. Clinical intervention strategies can benefit from better understanding research trends and adopting evidence-based practices in a more informed manner.

Impact of nutrient warning labels on Colombian consumers' selection and identification of food and drinks high in sugar, sodium, and saturated fat: A randomized controlled trial.

OBJECTIVE: This study assessed the impact of nutrient warnings on product selection and ability to identify food products high in nutrients of concern in Colombia. METHODS: In an online experiment (May-June 2023), Colombian adults were randomized to a nutrient warning, guideline daily amounts (GDA), Nutri-Score, or no-label condition (n = 8,004). Participants completed selection tasks between two fruit drinks labeled according to their condition, one high in sugar and one not. Next, participants answered questions about products high in sugar, sodium, and/or saturated fat ("high-in" product). Finally, they selected which label would most discourage them from consuming a high-in product. RESULTS: Fewer participants (17%) exposed to the nutrient warning indicated they would purchase the high-sugar fruit drink compared to Nutri-Score (27%, Holm-adjusted (adj) p<0.001) and no label conditions (31%, adj p<0.001); there were no differences between the nutrient warning and GDA label (14%, adj p = 0.087). Compared to the nutrient warning, the GDA label was slightly more effective at helping consumers identify which drink was high in sugar (89% versus 92%, adj p<0.001), while the Nutri-Score and no-label conditions were less effective. Compared to all other conditions, nutrient warnings were more effective at helping participants identify that products were high in nutrients of concern, were more effective at decreasing intentions to purchase these high-in products and were perceived as more effective. Nutrient warnings were most often selected as the label that most discouraged consumption. CONCLUSIONS: Nutrient warnings are a promising policy to help consumers identify and discourage consumption of products high in nutrients of concern. TRIAL REGISTRATION: Trial Registration: NCT05783726.

A boundary element method of bidomain modeling for predicting cellular responses to electromagnetic fields.

Objective.Commonly used cable equation approaches for simulating the effects of electromagnetic fields on excitable cells make several simplifying assumptions that could limit their predictive power. Bidomain or 'whole' finite element methods have been developed to fully couple cells and electric fields for more realistic neuron modeling. Here, we introduce a novel bidomain integral equation designed for determining the full electromagnetic coupling between stimulation devices and the intracellular, membrane, and extracellular regions of neurons.Approach.Our proposed boundary element formulation offers a solution to an integral equation that connects the device, tissue inhomogeneity, and cell membrane-induced E-fields. We solve this integral equation using first-order nodal elements and an unconditionally stable Crank-Nicholson time-stepping scheme. To validate and demonstrate our approach, we simulated cylindrical Hodgkin-Huxley axons and spherical cells in multiple brain stimulation scenarios.Main Results.Comparison studies show that a boundary element approach produces accurate results for both electric and magnetic stimulation. Unlike bidomain finite element methods, the bidomain boundary element method does not require volume meshes containing features at multiple scales. As a result, modeling cells, or tightly packed populations of cells, with microscale features embedded in a macroscale head model, is simplified, and the relative placement of devices and cells can be varied without the need to generate a new mesh.Significance.Device-induced electromagnetic fields are commonly used to modulate brain activity for research and therapeutic applications. Bidomain solvers allow for the full incorporation of realistic cell geometries, device E-fields, and neuron populations. Thus, multi-cell studies of advanced neuronal mechanisms would greatly benefit from the development of fast-bidomain solvers to ensure scalability and the practical execution of neural network simulations with realistic neuron morphologies.

LINC00662 Promotes Aggressive Traits by Modulating OCT4 Expression through miR-335-5p in Gallbladder Cancer Cells.

Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133+/CD44+ cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.

Influence of Polymeric Microparticle Size and Loading Concentration on 3D Printing Accuracy and Degradation Behavior of Composite Scaffolds.

Successful employment of 3D printing for delivery of therapeutic biomolecules requires protection of their bioactivity on exposure to potentially inactivating conditions. Although intermediary encapsulation of the biomolecules in polymeric particulate delivery vehicles is a promising strategy for this objective, the inclusion of such particles in 3D printing formulations may critically impact the accuracy or precision of 3D printed scaffolds relative to their intended designed architectures, as well as the degradation behavior of both the scaffolds and the included particles. The present work aimed to elucidate the effect of poly(d,l-lactic-co-glycolic acid) particle size and loading concentration on material accuracy, machine precision, and degradation of 3D printed poly(ɛ-caprolactone)-based scaffolds. Using a main effects analysis, the sizes and loading concentrations of particle delivery vehicles investigated were found to have neither a beneficial nor disadvantageous influence on the metrics of printing quality such as material accuracy and machine precision. Meanwhile, particle loading concentration was determined to influence degradation rate, whereas printing temperature affected the trends in composite weight-average molecular weight. Neither of the two particle-related parameters (concentration nor diameter) was found to exhibit a significant effect on intra-fiber nor inter-fiber porosity. These findings evidence the capacity for controlled loading of particulate delivery vehicles in 3D printed scaffolds while preserving construct accuracy and precision, and with predictable dictation of composite degradation behavior for potential controlled release of encapsulated biomolecules.

Influence of Alternative Prey on the Functional Response of a Predator in Two Contexts: With and without Intraguild Predation.

In biological control, joint releases of predators and parasitoids are standard. However, intraguild predation (IGP) can occur when a predator attacks a parasitoid, potentially affecting pest control dynamics. In addition to the focal prey (FP), Trialeurodes vaporariorum, the intraguild predator (IG-predator) Geocoris punctipes can consume the parasitoid Eretmocerus eremicus (IG-prey). In this IGP context with multiple prey, an alternative prey (AP), like the aphid Myzus persicae, may influence interactions. Theory predicts that, in simple interactions, a predator's functional response (FR) to the FP changes with the presence of an AP. However, whether this holds in an IGP context is unknown. In this study, we empirically tested that prediction. Our results show that without IGP, G. punctipes exhibits a generalized FR with and without AP. Nevertheless, with IGP, the predator exhibited a Type II FR at low and high AP densities, increasing pressure on the FP and potentially favoring short-term biological control strategies. However, when 25 AP were offered, the predator's response shifted, underscoring the importance of monitoring AP densities to prevent potential disruptions in FP control. In both contexts, the increase in AP produced a handling time increase and a decrease in consumption rate. These results indicate that the theoretical prediction of the effect of AP on the FR is met only under specific conditions, and the complexity of multitrophic interactions must be considered.

Editorial for the Special Issue on Biomaterials, Biodevices and Tissue Engineering.

Biomaterials, biodevices, and tissue engineering represent the cutting edge of medical science, promising revolutionary solutions to some of humanity's most pressing health challenges (Figure 1) [...].

A semi-automated pipeline for finite element modeling of electric field induced in nonhuman primates by transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) is used to treat a range of brain disorders by inducing an electric field (E-field) in the brain. However, the precise neural effects of TMS are not well understood. Nonhuman primates (NHPs) are used to model the impact of TMS on neural activity, but a systematic method of quantifying the induced E-field in the cortex of NHPs has not been developed. NEW METHOD: The pipeline uses statistical parametric mapping (SPM) to automatically segment a structural MRI image of a rhesus macaque into five tissue compartments. Manual corrections are necessary around implants. The segmented tissues are tessellated into 3D meshes used in finite element method (FEM) software to compute the TMS induced E-field in the brain. The gray matter can be further segmented into cortical laminae using a volume preserving method for defining layers. RESULTS: Models of three NHPs were generated with TMS coils placed over the precentral gyrus. Two coil configurations, active and sham, were simulated and compared. The results demonstrated a large difference in E-fields at the target. Additionally, the simulations were calculated using two different E-field solvers and were found to not significantly differ. COMPARISON WITH EXISTING METHODS: Current methods segment NHP tissues manually or use automated methods for only the brain tissue. Existing methods also do not stratify the gray matter into layers. CONCLUSION: The pipeline calculates the induced E-field in NHP models by TMS and can be used to plan implant surgeries and determine approximate E-field values around neuron recording sites.

Brain tumor detection using proper orthogonal decomposition integrated with deep learning networks.

BACKGROUND AND OBJECTIVE: The central organ of the human nervous system is the brain, which receives and sends stimuli to the various parts of the body to engage in daily activities. Uncontrolled growth of brain cells can result in tumors which affect the normal functions of healthy brain cells. An automatic reliable technique for detecting tumors is imperative to assist medical practitioners in the timely diagnosis of patients. Although machine learning models are being used, with minimal data availability to train, development of low-order based models integrated with machine learning are a tool for reliable detection. METHODS: In this study, we focus on comparing a low-order model such as proper orthogonal decomposition (POD) coupled with convolutional neural network (CNN) on 2D images from magnetic resonance imaging (MRI) scans to effectively identify brain tumors. The explainability of the coupled POD-CNN prediction output as well as the state-of-the-art pre-trained transfer learning models such as MobileNetV2, Inception-v3, ResNet101, and VGG-19 were explored. RESULTS: The results showed that CNN predicted tumors with an accuracy of 99.21% whereas POD-CNN performed better with about 1/3rd of computational time at an accuracy of 95.88%. Explainable AI with SHAP showed MobileNetV2 has better prediction in identifying the tumor boundaries. CONCLUSIONS: Integration of POD with CNN is carried for the first time to detect brain tumor detection with minimal MRI scan data. This study facilitates low-model approaches in machine learning to improve the accuracy and performance of tumor detection.

Machine learning classification based on k-Nearest Neighbors for PolSAR data.

In this work, we focus on obtaining insights of the performances of some well-known machine learning image classification techniques (k-NN, Support Vector Machine, randomized decision tree and one based on stochastic distances) for PolSAR (Polarimetric Synthetic Aperture Radar) imagery. We test the classifiers methods on a set of actual PolSAR data and provide some conclusions. The aim of this work is to show that suitable adapted standard machine learning methods offer excellent performances vs. computational complexity trade-off for PolSAR image classification. In this work, we evaluate well-known machine learning techniques for PolSAR (Polarimetric Synthetic Aperture Radar) image classification, including K-Nearest Neighbors (KNN), Support Vector Machine (SVM), randomized decision tree, and a method based on the Kullback-Leibler stochastic distance. Our experiments with real PolSAR data show that standard machine learning methods, when adapted appropriately, offer a favourable trade-off between performance and computational complexity. The KNN and SVM perform poorly on these data, likely due to their failure to account for the inherent speckle presence and properties of the studied reliefs. Overall, our findings highlight the potential of the Kullback-Leibler stochastic distance method for PolSAR image classification.

Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

Microsurgical management of radicular cyst using guided tissue regeneration technique: A case report.

BACKGROUND: Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic pulps. The therapeutic management of radicular cysts is controversial. There is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy, but without the use of the guided tissue regeneration (GTR) technique in the same surgical procedure. The present clinical case describes the management of a radicular cyst with microsurgical approach, performance of an apicoectomy of the tooth associated with the entity, application of GTR technique, use of a resorbable membrane of type I bovine collagen, and bovine xenograft. CASE SUMMARY: A 68-year-old patient presented with a radicular cyst from an upper lateral incisor. The microsurgical management used was aimed at enucleating the chemical membrane, performing apicoectomy of the tooth along with careful and precise retrograde filling, and implementing GTR technique using a resorbable collagen membrane and bovine xenograft. The diagnosis of radicular cyst was confirmed using histopathological analysis. The patient underwent follow-up evaluations at 10 and 30 d postoperatively. At 4 months postoperative evaluation, she remained asymptomatic, and radiographs showed significant periapical healing with adequate bone formation. CONCLUSION: These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft, contributes to bone regeneration.

Duration of biophysical profile in periviable and very preterm low-risk pregnancies.

BACKGROUND: In recent years, perinatal viability has shifted from 24 to 22 weeks of gestation at many institutions after improvements in survival in neonates delivered at the limit of viability. Monitoring these fetuses is essential because antenatal interventions with resuscitation efforts are available for patients at risk of delivery at the limit of viability. However, fetal monitoring using biophysical profiles has not been extensively studied in very preterm pregnancies, particularly in the periviable period (20 weeks 0 days to 23 weeks 6 days). OBJECTIVE: This study aimed to (1) investigate whether the completion of biophysical profiles within 30 minutes is feasible in very preterm pregnancies, and (2) determine the average observation time required to achieve a score of 8 out of 8 in very preterm pregnancies from 20 weeks 0 days to 31 weeks 6 days. STUDY DESIGN: This study prospectively evaluated biophysical scores in singleton pregnancies undergoing routine ultrasonography at or near viability from 20 weeks 0 days to 23 weeks 6 days (periviable or group I), 24 weeks 0 days to 27 weeks 6 days (group II), and 28 weeks 0 days to 31 weeks 6 days (group III). The results and duration of biophysical profiles were compared with those of a control group (32 weeks 0 days to 35 weeks 6 days) undergoing indicated fetal surveillance. Biophysical profiles were performed for all studied pregnancies until a score of 8 out of 8 was obtained. When >1 biophysical profile was obtained during pregnancy, each was analyzed individually. Pregnancies with fetal anomalies or obstetrical/medical indications for fetal well-being surveillance were excluded. Analysis of variance and post hoc Tukey tests were used for comparisons. RESULTS: Data were collected for 123 participants, yielding 79, 75, and 72 studies for groups I, II, and III, respectively. The control group included 42 patients, yielding 140 studies. At 30 minutes, 80% (63/79) of the studies in the periviable group had a score of 8 out of 8, as opposed to 100% (140/140) in the control group (P<.001). The mean±standard deviation time in minutes to achieve a biophysical score of 8 out of 8 was 23.3±10.1 in the periviable group, as opposed to 9.4±6.5 in controls (P<.001). Extending the study to +2 standard deviations (43.6 minutes) in the periviable group resulted in 97% (77/79) of the scans scoring 8 out of 8 in the absence of adverse outcomes. In the other groups, a biophysical score of 8 out of 8 within 30 minutes was obtained in 97% (73/75) and 100% (72/72) in groups II and III, respectively; the mean±standard deviation times were 17.1±8.4 minutes (group II) and 13.1±7.3 minutes (group III). No adverse outcomes developed during the study participation in groups I to III. CONCLUSION: Biophysical scores of 8 out of 8 can be successfully achieved in low-risk periviable pregnancies (20 weeks 0 days to 23 weeks 6 days) within an observation time longer than the standard 30-minute duration. The time required to reach a score of 8 out of 8 decreases as gestation progresses. We suggest adjusting the observation time for biophysical profile completion according to the gestational age.

Complex control of seed germination timing by ERF50 involves RGL2 antagonism and negative feedback regulation of DOG1.

Seed dormancy governs germination timing, with both evolutionary and applied consequences. Despite extensive studies on the hormonal and genetic control of these processes, molecular mechanisms directly linking dormancy and germination remain poorly understood. By screening a collection of lines overexpressing Arabidopsis transcription factors, we identified ERF50 as a key gene to control dormancy and germination. To study its regulation, we measured seed-related physiological parameters in loss-of-function mutants and carried out transactivation, protein interaction and ChIP-PCR analyses. We found direct ERF50-mediated repression of DOG1 and activation of EXPA2 transcription, which results in enhanced seed germination. Although ERF50 expression is increased by DOG1 in dormant seeds, ERF50 germination-promoting activity is blocked by RGL2. The physiological, genetic and molecular evidence gathered here supports that ERF50 controls germination timing by regulating DOG1 levels to leverage its role as enhancer of seed germination, via RGL2 antagonism on EXPA2 expression. Our results highlight the central role of ERF50 as a feedback regulator to couple and fine-tune seed dormancy and germination.

Does intradialytic oral nutrition impact hemodialysis patients' quality of life, appetite, and safety? A pilot study of a crossover clinical trial.

Introduction: Introduction: due to the catabolic characteristics of hemodialysis (HD), patients should consume foods or supplements during this treatment to meet their energy requirements and maintain a neutral nitrogen balance; however, there are some outcomes in which the effect of intradialytic oral nutrition (ION) is scarcely known. Objectives: this study aims to evaluate the effect of two types of ION (liquid and solid) on Quality of Life (QoL), appetite, and safety in HD patients. Methods: a pilot randomized, crossover clinical trial was performed in 18 patients on chronic HD. One group received ION for 18 HD sessions, after the crossover continued for 18 more sessions in the control group, and vice versa. We recorded QoL, appetite, systolic blood pressure (SBP), and intradialytic hypotension (IH) events. Results: clinical improvement was observed for most QoL components. Regardless of the consistency of supplementation, SBP increased to 4.10 mmHg. Both study groups reported a "very good-to-good" appetite. Conclusion: favorable clinical changes were observed in QoL scores during the study. Five of six IH events were reported for patients in the ION group, and SBP increased within the safe range (≤ 10 mmHg); appetite remained stable in both groups. Therefore, we concluded that this strategy, regardless of implementation consistency, is safe to be used in stable patients.

Introducción: Introducción: debido a las características catabólicas de la hemodiálisis (HD), los pacientes deben consumir alimentos o suplementos durante este tratamiento para cubrir sus requerimientos energéticos y mantener un balance nitrogenado neutro; sin embargo, existen algunos desenlaces en los que el efecto de la nutrición oral intradialítica (NOID) es poco conocido. Objetivo: este estudio tiene como objetivo evaluar el efecto de dos tipos de NOID (líquido y sólido) sobre la calidad de vida, el apetito y la seguridad en pacientes en HD. Métodos: se realizó un estudio piloto en forma de ensayo clínico aleatorizado y cruzado con 18 pacientes en HD crónica. Un grupo recibió NOID durante 18 sesiones de HD, después del cruzamiento continuaron durante 18 sesiones más en el grupo de control, y viceversa. Se registraron la calidad de vida, el apetito, la presión arterial sistólica (PAS) y la hipotensión intradialítica (HI). Resultados: se observó mejoría clínica en la mayoría de los componentes de la calidad de vida. Independientemente de la consistencia de la suplementación, la PAS aumentó hasta 4,10 mmHg. Ambos grupos de estudio informaron de un apetito "muy bueno-bueno". Conclusiones: se observaron cambios clínicos favorables en las puntuaciones de calidad de vida durante el estudio. Cinco de seis eventos de HI se reportaron en pacientes del grupo de NOID y la PAS aumentó dentro del rango seguro (≤ 10 mmHg); el apetito se mantuvo estable en ambos grupos. Por lo tanto, se puede concluir que esta estrategia, independientemente de la consistencia implementada, es segura para ser utilizada en pacientes estables.