Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Maternal Fish Oil and/or 5-Methyl-Tetrahydrofolate Supplementation during Pregnancy on Offspring Brain Resting-State at 10 Years Old: A Follow-Up Study from the NUHEAL Randomized Controlled Trial

Recent studies have shown that maternal supplementation with folate and long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy may affect children’s brain development. We aimed at examining the potential long-term effect of maternal supplementation with fish oil (FO) and/or 5-methyl-tetrahydrofolate (5-MTHF) on the brain functionality of offspring at the age of 9.5–10 years. The current study was conducted as a follow-up of the Spanish participants belonging to the Nutraceuticals for a Healthier Life (NUHEAL) project; 57 children were divided into groups according to mother’s supplementation and assessed through functional magnetic resonance imaging (fMRI) scanning and neurodevelopment testing. Independent component analysis and double regression methods were implemented to investigate plausible associations. Children born to mothers supplemented with FO (FO and FO + 5-MTHF groups, n = 33) showed weaker functional connectivity in the default mode (DM) (angular gyrus), the sensorimotor (SM) (motor and somatosensory cortices) and the fronto-parietal (FP) (angular gyrus) networks compared to the No-FO group (placebo and 5-MTHF groups, n = 24) (PFWE < 0.05). Furthermore, no differences were found regarding the neuropsychological tests, except for a trend of better results in an object recall (memory) test. Considering the No-FO group, the aforementioned networks were associated negatively with attention and speed-processing functions. Mother’s FO supplementation during pregnancy seems to be able to shape resting-state network functioning in their children at school age and appears to produce long-term effects on children´s cognitive processing.
Dynamic changes in DICER levels in adipose tissue control metabolic adaptations to exercise

Significance Aerobic exercise elicits an integrated metabolic response that involves multiple tissues and confers beneficial effects to metabolic health. Here we found that this integrative response involves energy-sensing pathways in muscle and fat and circulating factors that lead to the upregulation of the type III endoribonuclease DICER in adipose tissue and the consequent increase of microRNAs. Upon upregulation, DICER and the microRNA-203-3p inhibit glucose utilization by fat cells and favor oxidative metabolism. In turn, this supports the exercised muscle with adequate substrate availability. When this pathway is disrupted, whole-body metabolism is affected, and exercise performance is impaired. Thus, adipose tissue DICER integrates signals from the exercising muscle to allow a proper metabolic response to exercise training. DICER is a key enzyme in microRNA (miRNA) biogenesis. Here we show that aerobic exercise training up-regulates DICER in adipose tissue of mice and humans. This can be mimicked by infusion of serum from exercised mice into sedentary mice and depends on AMPK-mediated signaling in both muscle and adipocytes. Adipocyte DICER is required for whole-body metabolic adaptations to aerobic exercise training, in part, by allowing controlled substrate utilization in adipose tissue, which, in turn, supports skeletal muscle function. Exercise training increases overall miRNA expression in adipose tissue, and up-regulation of miR-203-3p limits glycolysis in adipose under conditions of metabolic stress. We propose that exercise training-induced DICER-miR-203-3p up-regulation in adipocytes is a key adaptive response that coordinates signals from working muscle to promote whole-body metabolic adaptations.
Immune-checkpoint inhibitors plus chemotherapy versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer

We performed a meta-analysis to comprehensively investigate the efficacy and safety of immune-checkpoint inhibitors (ICIs) plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and ≥grade 3 adverse events (AEs). A total of six studies involving 2905 patients were identified, including 469 patients receiving program death ligand 1 (PD-L1) inhibitor plus chemotherapy, 308 receiving PD-1 inhibitors plus chemotherapy, 563 receiving CTLA-4 inhibitors plus chemotherapy, 268 receiving PD-L1/CTLA-4 inhibitors plus chemotherapy, and 1297 receiving chemotherapy alone. 10.8% (283/2615) patients had baseline brain metastases (BMs). Notably, ICIs plus chemotherapy was associated with significantly improved OS (HR, 0.82; 95% CI, 0.75 to 0.89). Subgroup analyses revealed that PD-1 inhibitors (HR, 0.77; 95% CI, 0.64 to 0.92) and PD-L1 inhibitors (HR, 0.73; 95% CI, 0.63 to 0.85) plus chemotherapy yielded a statistically significant improvement in OS while CTLA-4 inhibitors did not (HR, 0.92; 95% CI, 0.81 to 1.06). In patients with baseline BMs, ICIs plus chemotherapy showed no survival benefits over chemotherapy alone (HR, 1.23; 95% CI, 0.92 to 1.64). ICIs plus chemotherapy also significantly prolonged PFS (HR, 0.81; 95% CI, 0.75 to 0.87) while the pooled ORRs were comparable between ICIs plus chemotherapy and chemotherapy alone (RR, 1.04; 95% CI, 0.99 to 1.10). Patients treated with CTLA-4 inhibitors (relative risk (RR), 1.12; 95% CI, 0.99 to 1.28) experienced more≥grade 3 AEs than those treated with PD-1/PD-L1 inhibitors (RR, 1.03; 95% CI, 0.96 to 1.11). The addition of PD-1/PD-L1 inhibitors to chemotherapy resulted in significant improvements in both PFS and OS for patients with treatment-naïve ES-SCLC, not at the cost of increased AEs.
Optimization and Communication in UAV Networks

Nowadays, Unmanned Aerial Vehicles (UAVs) have received growing popularity in the Internet-of-Things (IoT) which often deploys many sensors in a relatively wide region. Current trends focus on deployment of a single UAV or a swarm of it to generally map an area, perform surveillance, monitoring or rescue operations, collect data from ground sensors or various communicating devices, provide additional computing services close to data producers, etc. Applications are very diverse and call for different features or requirements. But UAV remain low-power battery powered devices that in addition to their mission, must fly and communicate. Thanks to wireless communications, they participate to mobile dynamic networks composed of UAV and ground sensors and thus many challenges have to be addressed to make UAV very efficient. And behind any UAV application, hides an optimization problem. There is still a criterion or multiple ones to optimize such as flying time, energy consumption, number of UAV, quantity of data to send/receive, etc.
Managing Rhizoctonia Damping-Off of Rocket (Eruca sativa) Seedlings by Drench Application of Bioactive Potato Leaf Phytochemical Extracts

Plants produce a huge array of secondary metabolites that play a key role in defense mechanisms against detrimental microorganisms and herbivores, and represent a suitable alternative to synthetic fungicides in sustainable agriculture. In this work, twelve crude hydroethanolic extracts derived from leaves of different potato cultivars were chemically characterized by LC/MS and their antioxidant properties were investigated in vitro. Furthermore, the biological activity against the fungal pathogen Rhizoctonia solani was evaluated both in vitro and in vivo. Extracts showed the ability to inhibit R. solani growth in vitro and significantly reduced damping-off incidence in in vivo experiments. Furthermore, R. solani mycelia exposed to the extracts showed an altered morphology (low translucency, irregular silhouette, and cytoplasmatic content coagulation) compared to the untreated control in light microscopy examination. Principal component analysis conducted on identified chemical compounds highlighted significant metabolic variations across the different extracts. In particular, those that inhibited most of the growth of the pathogen were found to be enriched in α-chaconine or α-solanine content, indicating that their biological activity is affected by the abundance of these metabolites. These results clearly indicated that plant-derived compounds represent a suitable alternative to chemicals and could lead to the development of new formulates for sustainable control of plant diseases.
Roles of dispersal and predation in determining seedling recruitment patterns in a foundational marine angiosperm

Seed dispersal and seed predation are 2 important processes in the early life history of plants. These mechanisms have been described extensively in terrestrial plants and have resulted in the creation of various models to describe seedling recruitment with increasing distance from the parent plant. However, it is unclear whether theoretical models derived from terrestrial studies apply to marine angiosperms. We performed observational and experimental tests of seed dispersal mechanisms in a marine environment to elucidate patterns of seed dispersal and predation in a foundational marine angiosperm, eelgrass Zostera marina. We also modeled seed dispersal and predation to explore how recruitment varies under different scenarios of predator activity and abundance. We found that seed densities were highest within and adjacent to vegetated areas. Predation pressure was low overall, and there was no significant difference in predation pressure between vegetated and unvegetated areas. Seedling densities were highly correlated with seed densities from the previous year, suggesting that seed predation had a limited impact on population recruitment. These results are consistent with the invariant survival model, which states that seed survivorship has no spatial trend. The theoretical scenarios we generated suggest that a low abundance of highly mobile, generalist predators may explain the patterns observed in our system. Therefore, seedling establishment rates are almost solely attributable and inversely proportional to distance from the parent plant. The results from this study have important implications for the recovery and restoration of these highly threatened coastal ecosystems.
Pyrazole-Based Lactate Dehydrogenase Inhibitors with Optimized Cell Activity and Pharmacokinetic Properties

Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate to lactate, with concomitant oxidation of reduced nicotinamide adenine dinucleotide as the final step in the glycolytic pathway. Glycolysis plays an important role in the metabolic plasticity of cancer cells and has long been recognized as a potential therapeutic target. Thus, potent, selective inhibitors of LDH represent an attractive therapeutic approach. However, to date, pharmacological agents have failed to achieve significant target engagement in vivo, possibly because the protein is present in cells at very high concentrations. We report herein a lead optimization campaign focused on a pyrazole-based series of compounds, using structure-based design concepts, coupled with optimization of cellular potency, in vitro drug–target residence times, and in vivo PK properties, to identify first-in-class inhibitors that demonstrate LDH inhibition in vivo. The lead compounds, named NCATS-SM1440 (43) and NCATS-SM1441 (52), possess desirable attributes for further studying the effect of in vivo LDH inhibition.
The relationship between hyperglycemia and the infection of COVID-19 in diabetic patients

Abstract Background: DM is a common chronic metabolic disease. COVID-19 is an infectious disease infected by enveloped single-stranded RNA coronavirus. Meanwhile, DM is a common comorbidity of SARS-CoV-2 infection. The virus can directly or indirectly damage the pancreatic islets and cause stress hyperglycemia by causing cytokine storms, acute inflammatory reactions, binding to the ACE2 receptor, etc. At the same time, hyperglycemia is a risk factor for severe infection and an independent risk factor for mild to severe disease. However, there is no evidence-based medicine to confirm the relationship between hyperglycemia and the infection of COVID-19 in diabetic patients. Therefore, we will conduct a systematic review and meta-analysis to synthesize the existing clinical evidence. Methods and analysis: We will retrieve each database from December 2019 to July 2020. Chinese literature comes from CNKI, Wanfang, VIP, CBM databases. English literature mainly searches Cochrane Library, PubMed, Web of Science, EMBASE. At the same time, we will look for clinical trial registration and gray literature. This study only included clinical randomized controlled trials. The reviewers independently conduct literature selection, data analysis, bias risk assessment, subgroup and sensitivity analysis. The primary outcomes include fasting blood glucose, 2-hour postprandial blood glucose, glycated hemoglobin, fasting insulin, adverse effects, etc. Finally, we will conduct a meta-analysis through Review Manager software version 5.3. Results: The results will be published in peer-reviewed journals. Conclusion: This study will explore the relationship between hyperglycemia and COVID-19 infection in diabetic patients. It will provide evidence-based support for clinical regulation of blood glucose and combating the COVID-19 epidemic. Registration number: INPLASY202060114
Broadband Lumped-Element Parameter Extraction Method of Two-Port 3D MEMS In-Chip Solenoid Inductors Based on a Physics-Based Equivalent Circuit Model

Integrated 2D spiral inductors possess low inductance per unit area, which limits their application range. However, the state of investigation into the lumped-element parameter extraction method for integrated 3D in-chip multi-turn solenoid inductors, which possess higher inductance per unit area, is inadequate. This type of inductor can thus not be incorporated into fast computer-aided design (CAD)-assisted circuit design. In this study, we propose a broadband two-port physics-based equivalent circuit model for 3D microelectromechanical system (MEMS) in-chip solenoid inductors that are embedded in silicon substrates. The circuit model was composed of lumped elements with specific physical meanings and incorporated complicated parasitics resulting from eddy currents, skin effects, and proximity effects. Based on this model, we presented a lumped-element parameter extraction method using the electronic design automation software package, Agilent Advanced Design System (ADS). This method proved to be consistent with the results of two-port testing at low to self-resonant frequencies and could thus be used in CAD-assisted circuit design. The lumped element value variations were analyzed based on the physical meaning of the elements with respect to variations in structures and the substrate resistivity of inductors. This provided a novel perspective in terms of the design of integrated in-chip solenoid inductors.
Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA

Hybrid nanoparticles from lipidic and polymeric components were assembled to serve as vehicles for the transfection of messenger RNA (mRNA) using different portions of the cationic lipid DOTAP (1,2-Dioleoyl-3-trimethylammonium-propane) and the cationic biopolymer protamine as model systems. Two different sequential assembly approaches in comparison with a direct single-step protocol were applied, and molecular organization in correlation with biological activity of the resulting nanoparticle systems was investigated. Differences in the structure of the nanoparticles were revealed by thorough physicochemical characterization including small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). All hybrid systems, combining lipid and polymer, displayed significantly increased transfection in comparison to lipid/mRNA and polymer/mRNA particles alone. For the hybrid nanoparticles, characteristic differences regarding the internal organization, release characteristics, and activity were determined depending on the assembly route. The systems with the highest transfection efficacy were characterized by a heterogenous internal organization, accompanied by facilitated release. Such a system could be best obtained by the single step protocol, starting with a lipid and polymer mixture for nanoparticle formation.
Human model of IRX5 mutations reveals key role for this transcription factor in ventricular conduction.

AIM Several inherited arrhythmic diseases have been linked to single gene mutations in cardiac ion channels and interacting proteins. However, the mechanisms underlying most arrhythmias, are thought to involve altered regulation of the expression of multiple effectors. In this study, we aimed to examine the role of a transcription factor belonging to the Iroquois homeobox family, IRX5, in cardiac electrical function. METHODS AND RESULTS Using human cardiac tissues, transcriptomic correlative analyses between IRX5 and genes involved in cardiac electrical activity showed that in human ventricular compartment, IRX5 expression strongly correlated to the expression of major actors of cardiac conduction, including the sodium channel, Nav1.5, and Connexin 40 (Cx40). We then generated human induced pluripotent stem cells (hiPSCs) derived from two Hamamy Syndrome-affected patients carrying distinct homozygous loss-of-function mutations in IRX5 gene. Cardiomyocytes derived from these hiPSCs showed impaired cardiac gene expression program, including misregulation in the control of Nav1.5 and Cx40 expression. In accordance with the prolonged QRS interval observed in Hamamy Syndrome patients, a slower ventricular action potential depolarization due to sodium current reduction was observed on electrophysiological analyses performed on patient-derived cardiomyocytes, confirming the functional role of IRX5 in electrical conduction. Finally, a novel cardiac transcription factor complex was identified, composed by IRX5 and GATA4, in which IRX5 potentiated GATA4-induction of SCN5A expression. CONCLUSIONS Altogether, this work unveils a key role for IRX5 in the regulation of human ventricular depolarization and cardiac electrical conduction, providing therefore new insights into our understanding of cardiac diseases. TRANSLATIONAL PERSPECTIVES Inherited cardiac arrhythmias account for about 20% of sudden cardiac deaths, of which a small portion are monogenic familial diseases with mutations in cardiac ion channels. However, pathogeny of inherited cardiac arrhythmias is increasingly thought to result from complex mechanisms involving altered regulation of multiple effectors expression. Taking advantage of cardiomyocytes derived from Hamamy syndrome patients, carrying loss-of-function mutations in IRX5 transcription factor, we uncovered an important role for IRX5 in the regulation of several major players of ventricular depolarization conduction and in arrhythmogenesis. Thus, this study supports systematic screening for genetic variants in IRX5 in inherited cardiac arrhythmias.
Dental Adhesive Interfaces Reinforced with Magnetic Nanoparticles: Evaluation and Modeling with Micro-CT versus Optical Microscopy

Dental adhesives are used in a wide range of applications, including to place direct composite restorations in frontal or posterior teeth. One of the most frequent causes for the failure of composite resin restorations is microleakages. The first aim of this work is to introduce a new type of self-etched dental adhesive doped with magnetic nanoparticles (MPs) synthetized in the laboratory. The scope is to produce adhesives with a minimized width/thickness to decrease the risk of microleakages. The second aim is to assess the width/thickness of the adhesive layer in all the characteristic areas of the teeth using both the less precise but most common optical microscopy and the more accurate and volumetric micro-Computed Tomography (CT) investigations. Twenty extracted teeth have been divided into four groups: Group 1 includes ‘blank’ samples with adhesives that are not doped with MPs; Group 2 includes samples with adhesives doped with MPs; Groups 3 and 4 include samples with adhesives doped with MPs that are subjected to an active magnetic field for 5 and 10 min, respectively. Microscopy investigations followed by micro-CT and EDAX are performed on the adhesive. While a rather good agreement is obtained between the microscopy and micro-CT results, the capability of the latter to offer a full volumetric reconstruction of the layer is exploited to analyze the adhesion of the four considered dental materials. Thus, from micro-CT results the graphs of the surface areas as functions of the adhesive layer width are modeled mathematically, as well as the volume of sealants, for each of the four groups. To our knowledge, it is the first time that such a methodology is used. Characteristic parameters are extracted and the ascertainment of the optimal parameter that should be utilized for such assessments is discussed. The study demonstrates the adhesion improvement produced for Groups 3 and 4, where MPs are used. It also concludes that the magnetic field should be applied to the adhesive material for the longest possible exposure time (with a trade-off with the clinical duration of the treatment).
Evaluation of In vitro Antioxidant and In vivo Antihyperlipidemic Activities of Methanol Extract of Aerial Part of Crassocephalum crepidioides (Asteraceae) Benth S Moore

Purpose: To evaluate the antioxidant and antihyperlipidemic activities of the methanol extract of aerial part of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore. Methods: The methanol extract of Crassocephalum crepidioides was prepared by organic solvent extraction (Maceration) and assessed for in vitro antioxidant activity using various methods, namely, 2,2 diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, total phenol and flavonoid content and reducing capacity. The extract was also evaluated for antihyperlipidemic activity in high-fat diet and triton WR-100 (iso-octyl polyoxyethylene phenol)-induced hyperlipidemic albino rats by evaluating serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), very low density lipoprotein cholesterol (VLDL-c), low-density lipoprotein cholesterol (LDL-c) level and atherogenic index (AI). Results: The plant extract showed significant antioxidant activity in a dose-dependent manner. In highfat diet hyperlipedemic rats, the extract significantly reduced ( p < 0.01 or 0.001) serum TC, TG, LDL-c and VLDL-c levels, but significantly increased ( p < 0.05) serum HDL c level. In triton-induced hyperlipidemic rats, the extract significantly reduced ( p < 0.05, p < 0.01, p < 0.001) serum TC, TG, LDLc, VLDL-c levels but significantly increased ( p < 0.05) serum HDL-c level. The extract showed significant reduction ( p < 0.01) in AI at 300 mg /kg/day dose in both high fat-induced (1.70 ± 0.25) and tritoninduced (1.5 ± 0.17) hyperlipidemic albino rats. Conclusion: Based on these findings, the extract of Crassocephalum crepidioides aids in lowering hyperlipidemia in rats. This is probably due to its antioxidant activity. Keywords: Antioxidant, Antihyperlipidemic, Crassocephalum crepidioides , Triton WR-100, Atherogenic index