Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatial Patterns of Potentially Hazardous Metals in Soils of Lin’an City, Southeastern China

Urban soils are strongly related to human health. In this study, Lin’an city was chosen as a typical small-scale city with which to study the spatial variation of potentially hazardous metals (PHMs) in urban soils and their potential ecological risks using multivariate analysis, geostatistics and GIS techniques. A total of 62 soil samples were collected from the study area. The results showed that the average concentrations of total soil Mn, Cu, Zn, Pb, Cr, Cd were 439.42, 42.23, 196.80, 62.55, 63.65, 0.22 mg·kg−1, respectively. Compared with the background values and the environmental quality standards, these PHMs were accumulated in urban soils to some extent. The single potential ecological risk indices of PHMs indicated that Pb and Cd had relatively high ecological risks. The pH and most of the PHMs had significant correlations (p < 0.05). The principle components analysis (PCA) showed that Pb, Zn and Cu had similar pollution sources related to the vehicles’ exhaust emission; Mn and Cr were mainly from the parent materials; while Cd was from the emission of industrial manufactories. The spatial structures and distributions of PHMs and their corresponding available fractions had strong/moderate spatial autocorrelation, which were influenced by human activities.
Lipid Peroxidation Drives Renal Cyst Growth In Vitro through Activation of TMEM16A.

BACKGROUND Transepithelial chloride- secretion, through the chloride channels cystic fibrosis transmembrane conductance regulator (CFTR) and TMEM16A (anoctamin 1), drives cyst enlargement in polycystic kidney disease (PKD). Polycystic kidneys are hypoxic, and oxidative stress activates TMEM16A. However, mechanisms for channel activation in PKD remain obscure. METHODS Using tissue samples from patients with autosomal dominant PKD, embryonic kidney cultures, and an MDCK in vitro cyst model, we assessed peroxidation of plasma membrane phospholipids in human and mouse polycystic kidneys. We also used electrophysiologic Ussing chamber and patch clamp experiments to analyze activation of TMEM16A and growth of renal cysts. RESULTS Peroxidation of phospholipids in human and mouse kidneys as well as MDCK cysts in vitro is probably due to enhanced levels of reactive oxygen species. Lipid peroxidation correlated with increased cyst volume as shown in renal cultures and MDCK cysts in three-dimensional cultures. Reactive oxygen species and lipid peroxidation strongly activated TMEM16A, leading to depletion of calcium ion stores and store-operated calcium influx. Activation of TMEM16A- and CFTR-dependent chloride secretion strongly augmented cyst growth. Exposure to scavengers of reactive oxygen species, such as glutathione, coenzyme Q10, or idebenone (a synthetic coenzyme Q10 homolog), as well as inhibition of oxidative lipid damage by ferrostatin-1 largely reduced activation of TMEM16A. Inhibition of TMEM16A reduced proliferation and fluid secretion in vitro. CONCLUSIONS These findings indicate that activation of TMEM16A by lipid peroxidation drives growth of renal cysts. We propose direct inhibition of TMEM16A or inhibition of lipid peroxidation as potentially powerful therapeutic approaches to delay cyst development in PKD.
Using Moderator Analysis to Identify the First-Grade Children Who Benefit More and Less From a Reading Comprehension Program: A Step Toward Aptitude-by-Treatment Interaction

Because of the importance of teaching reading comprehension to struggling young readers and the infrequency with which it has been implemented and evaluated, we designed a comprehensive first-grade reading comprehension program. We conducted a component analysis of the program’s decoding/fluency and reading comprehension dimensions (DF and COMP), creating DF and DF+COMP treatments to parse the value of COMP. Students (N = 125) were randomly assigned to the two active treatments and controls. Treatment children were tutored three times per week for 21 weeks in 45-min sessions. Children in DF and DF+COMP together performed more strongly than controls on word reading and comprehension. However, pretreatment word reading appeared to moderate these results such that children with weaker beginning word reading across the treatments outperformed similarly low-performing controls to a significantly greater extent than treatment children with stronger beginning word reading outperformed comparable controls. DF+COMP children did not perform better than DF children. Study limitations and implications for research and practice are discussed.
A large nested association mapping population for breeding and quantitative trait locus mapping in Ethiopian durum wheat

Summary The Ethiopian plateau hosts thousands of durum wheat (Triticum turgidum subsp. durum) farmer varieties (FV) with high adaptability and breeding potential. To harness their unique allelic diversity, we produced a large nested association mapping (NAM) population intercrossing fifty Ethiopian FVs with an international elite durum wheat variety (Asassa). The Ethiopian NAM population (EtNAM) is composed of fifty interconnected bi‐parental families, totalling 6280 recombinant inbred lines (RILs) that represent both a powerful quantitative trait loci (QTL) mapping tool, and a large pre‐breeding panel. Here, we discuss the molecular and phenotypic diversity of the EtNAM founder lines, then we use an array featuring 13 000 single nucleotide polymorphisms (SNPs) to characterize a subset of 1200 EtNAM RILs from 12 families. Finally, we test the usefulness of the population by mapping phenology traits and plant height using a genome wide association (GWA) approach. EtNAM RILs showed high allelic variation and a genetic makeup combining genetic diversity from Ethiopian FVs with the international durum wheat allele pool. EtNAM SNP data were projected on the fully sequenced AB genome of wild emmer wheat, and were used to estimate pairwise linkage disequilibrium (LD) measures that reported an LD decay distance of 7.4 Mb on average, and balanced founder contributions across EtNAM families. GWA analyses identified 11 genomic loci individually affecting up to 3 days in flowering time and more than 1.6 cm in height. We argue that the EtNAM is a powerful tool to support the production of new durum wheat varieties targeting local and global agriculture.
LGM2605 Reduces Space Radiation-Induced NLRP3 Inflammasome Activation and Damage in In Vitro Lung Vascular Networks

Updated measurements of charged particle fluxes during the transit from Earth to Mars as well as on site measurements by Curiosity of Martian surface radiation fluxes identified potential health hazards associated with radiation exposure for human space missions. Designing mitigation strategies of radiation risks to astronauts is critical. We investigated radiation-induced endothelial cell damage and its mitigation by LGM2605, a radioprotector with antioxidant and free radical scavenging properties. We used an in vitro model of lung vascular networks (flow-adapted endothelial cells; FAECs), exposed to gamma rays, low/higher linear energy transfer (LET) protons (3–4 or 8–10 keV/µm, respectively), and mixed field radiation sources (gamma and protons), given at mission-relevant doses (0.25 gray (Gy)–1 Gy). We evaluated endothelial inflammatory phenotype, NLRP3 inflammasome activation, and oxidative cell injury. LGM2605 (100 µM) was added 30 min post radiation exposure and gene expression changes evaluated 24 h later. Radiation induced a robust increase in mRNA levels of antioxidant enzymes post 0.25 Gy and 0.5 Gy gamma radiation, which was significantly decreased by LGM2605. Intercellular cell adhesion molecule-1 (ICAM-1) and NOD-like receptor protein 3 (NLRP3) induction by individual or mixed-field exposures were also significantly blunted by LGM2605. We conclude that LGM2605 is a likely candidate to reduce tissue damage from space-relevant radiation exposure.
Comparison Between Continuous and Intermittent Administration of Hydrocortisone During Septic Shock: A Randomized Controlled Clinical Trial.

OBJECTIVES the best modality of administration of hydrocortisone during septic shock has been poorly evaluated and the guidelines remain unclear in this respect. This study aimed to compare bolus of hydrocortisone to a continuous infusion during septic shock. DESIGN randomized controlled, open-label trial. SETTING medical ICU of a university hospital. PATIENTS adult patients with septic shock requiring more than 2 mg/h (approximately 33.3 μg/mn) of norepinephrine after adequate fluid administration were eligible.Patients already receiving corticosteroids or who have a contraindication to corticosteroids, patients who died within 24 hours and those with a decision of not to resuscitate were excluded. INTERVENTIONS Patients were randomized either to receive hydrocortisone 200 mg/day by continuous infusion or by boluses of 50 mg every 6 hours for a maximum of 7 days or whenever vasoactive drugs are stopped. RESULTS Twenty nine patients were included in each group. Shock reversal was significantly higher in the HC bolus group (75% Vs. 44%, p = 0.01). The median time to shock reversal was 6 days (95% CI, 4.5 - 7.49) in the HC bolus group compared to 9 days (95% CI, 2.06 - 15.93) in the HC continuous infusion group with no significant difference (log Rank = 0.133). The number of hours spent with blood glucose ≥ 180 mg/dl was higher in the HC continuous infusion group with a median of 64 hours [IQR (2-100)] versus 48 hours [IQR (14-107)] in the HC bolus group, (p = 0.60), and daily insulin requirements were similar between the two groups, (p = 0.63). The occurrence of other side effects, mortality and ICU LOS were similar between the study groups. CONCLUSION Hydrocortisone administered by intermittent bolus was associated with higher shock reversal at day 7 compared with a continuous infusion.
The human RNA helicase DHX37 is required for release of the U3 snoRNP from pre-ribosomal particles

ABSTRACT Ribosome synthesis is an essential cellular process, and perturbation of human ribosome production is linked to cancer and genetic diseases termed ribosomopathies. During their assembly, pre-ribosomal particles undergo numerous structural rearrangements, which establish the architecture present in mature complexes and serve as key checkpoints, ensuring the fidelity of ribosome biogenesis. RNA helicases are essential mediators of such remodelling events and here, we demonstrate that the DEAH-box RNA helicase DHX37 is required for maturation of the small ribosomal subunit in human cells. Our data reveal that the presence of DHX37 in early pre-ribosomal particles is monitored by a quality control pathway and that failure to recruit DHX37 leads to pre-rRNA degradation. Using an in vivo crosslinking approach, we show that DHX37 binds directly to the U3 small nucleolar RNA (snoRNA) and demonstrate that the catalytic activity of the helicase is required for dissociation of the U3 snoRNA from pre-ribosomal complexes. This is an important event during ribosome assembly as it enables formation of the central pseudoknot structure of the small ribosomal subunit. We identify UTP14A as a direct interaction partner of DHX37 and our data suggest that UTP14A can act as a cofactor that stimulates the activity of the helicase in the context of U3 snoRNA release.
Identification of differentially expressed genes and biological characteristics of colorectal cancer by integrated bioinformatics analysis

Colorectal cancer (CRC) ranks as one of the most common malignant tumors worldwide. Its mortality rate has remained high in recent years. Therefore, the aim of this study was to identify significant differentially expressed genes (DEGs) involved in its pathogenesis, which may be used as novel biomarkers or potential therapeutic targets for CRC. The gene expression profiles of GSE21510, GSE32323, GSE89076, and GSE113513 were downloaded from the Gene Expression Omnibus (GEO) database. After screening DEGs in each GEO data set, we further used the robust rank aggregation method to identify 494 significant DEGs including 212 upregulated and 282 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by DAVID and the KOBAS online database, respectively. These DEGs were shown to be significantly enriched in different cancer‐related functions and pathways. Then, the STRING database was used to construct the protein–protein interaction network. The module analysis was performed by the MCODE plug‐in of Cytoscape based on the whole network. We finally filtered out seven hub genes by the cytoHubba plug‐in, including PPBP, CCL28, CXCL12, INSL5, CXCL3, CXCL10, and CXCL11. The expression validation and survival analysis of these hub genes were analyzed based on The Cancer Genome Atlas database. In conclusion, the robust DEGs associated with the carcinogenesis of CRC were screened through the GEO database, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for CRC.
Neutrophil Extracellular Traps in Arterial and Venous Thrombosis

Abstract Thrombotic complications are still a major health risk worldwide. Our view on the pathophysiology of thrombosis has significantly changed since the discovery of neutrophil extracellular traps (NETs) and their prothrombotic characteristics. Generated by neutrophils that release their decondensed chromatin as a network of extracellular fibers, NETs promote thrombus formation by serving as a scaffold that activates platelets and coagulation. The thrombogenic involvement of NETs has been described in various settings of thrombosis, including stroke, myocardial infarction, and deep vein thrombosis. The aim of this review is to summarize existing evidence showing the presence of NETs in human thrombus material. Following an introduction on NETs and their role in thrombus formation, the authors address studies showing the presence of NETs in arterial or venous thrombi. In addition, they focus on potential novel therapeutic opportunities to resolve or prevent thrombosis by targeting NETs.
Efficiency distribution and expected efficiencies in DEA with imprecise data

Several methods have been proposed for ranking the decision-making units (DMUs) in data envelopment analysis (DEA) with imprecise data. Some methods have only used the upper bound efficiencies to rank DMUs. However, some other methods have considered both of the lower and upper bound efficiencies to rank DMUs. The current paper shows that these methods did not consider the DEA axioms and may be unable to produce a rational ranking. We show that considering the imprecise data as stochastic and using the expected efficiencies to rank DMUs give better results. Indeed, we propose a new ranking approach, based on considering the DEA axioms for imprecise data that removes the existing drawbacks. Some numerical examples are provided to explain the content of the paper.
Age-Dependent Expression of MyHC Isoforms and Lipid Metabolism-Related Genes in the Longissimus Dorsi Muscle of Wild and Domestic Pigs

Simple Summary This comparative study found that postnatal myofiber differentiation in the longissimus dorsi muscle of wild pigs was accelerated and directed toward oxidative myofibers in which the MyHC-I, -IIa and -IIx genes were well expressed. In domestic pigs, the transformation was directed toward glycolytic myofibers in which the MyHC-IIb gene transcript was abundant. The myofiber succinate dehydrogenase (SDH) activity and lipid content reflected expression patterns of the MyHCs and not genes involved in lipid uptake and utilization (PGC-1α, PPARγ, LPL, and CPT-1B). MyHC myofiber characteristics reflect the effects of selection pressure and rearing conditions on the growth and lean meat content and may be valuable for establishing a balanced breeding scheme focused on improving meat quality traits. Abstract This study aimed to compare age-dependent changes in the relative expression of genes encoding myosin heavy chain (MyHC) isoforms and selected lipid metabolism-related genes in the longissimus dorsi muscle of wild pigs (WPs) and domestic pigs (DPs). Muscles sampled from postnatal day one as well as three-week-old and two-year-old animals were used in quantitative polymerase chain reaction (qPCR) assays, histological evaluations of succinate dehydrogenase (SDH) activity, and intra-myofiber lipid (IMFL) assessment. Expression of the MyHC isoforms displayed the most extensive age- and breed-dependent changes within the first three postnatal weeks. The MyHCembry level decreased significantly faster in the WPs than in the DPs. The relative MyHC-I and -IIa expression was significantly higher in the WPs, and MyHC-IIb was substantially higher in the DPs. The differences in MyHC expression corroborated the number of SDH-positive myofibers and IMFLs. Expression of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) genes displayed only age-related variations. In summary, the evidence is provided for accelerated postnatal myofiber transformation directed towards oxidative myofibers in WPs. The SDH activity/staining intensity largely reflected the expression of MyHCs, and not genes involved in lipid uptake and utilization.
Temporal Modulation of Steady-State Visual Evoked Potentials

Electroencephalographic responses to periodic stimulation are termed steady-state visual evoked potentials (SSVEP). Their characteristics in terms of amplitude, frequency and phase are commonly assumed to be stationary. In this work, we tested this assumption in 30 healthy participants submitted to 50 trials of 60 s flicker stimulation at 15 Hz frequency. We showed that the amplitude of the first and second harmonic frequency components of SSVEP signals were in general not stable over time. The power (squared amplitude) of the fundamental component was stationary only in 30% the subjects, while the power at the second harmonic frequency was stationary in 66.7% of the group. The phases of both SSVEP frequency components were more stable over time, but could exhibit small drifts. The observed temporal changes were heterogeneous across the subjects, implying that averaging results over participants should be performed carefully. These results may contribute to improved design and analysis of experiments employing prolonged visual stimulation. Our findings offer a novel characterization of the temporal changes of SSVEP that may help to identify their physiological basis.
Pediatric Nasoorbitoethmoid Fractures: Cause, Classification, and Management

Background: Currently, there is a paucity of information on the presentation and proper management of pediatric nasoorbitoethmoid fractures. The purpose of this study was to examine the incidence, cause, associated injuries, and management of these fractures. Furthermore, the authors sought to assess outcomes after transnasal wiring or suture canthopexy for type III nasoorbitoethmoid fractures. Methods: A retrospective cohort review was performed of all patients with nasoorbitoethmoid fractures who presented to a Level I trauma center from 1990 to 2010. Charts and computed tomographic imaging were reviewed, and nasoorbitoethmoid fractures were labeled based on the Markowitz-Manson classification system. Patient fracture patterns, demographics, characteristics, and outcomes were recorded. Univariate and multivariate methods were used to compare groups. Results: A total of 63 pediatric patients were identified in the study period. The sample’s mean age was 8.78 ± 4.08 years, and 28.6 percent were girls. The sample included 18 type I injuries, 28 type II injuries, and 17 type III injuries. No significant demographic differences were found between patients with type I, II, and III fractures (p > 0.05). Operative intervention was pursued in 16.7, 46.4, and 82.4 percent of type I, II, and III nasoorbitoethmoid fractures, respectively. In patients with type III nasoorbitoethmoid fractures, no patients with transnasal wiring developed telecanthus. Conclusions: Pediatric nasoorbitoethmoid fractures are uncommon injuries. Type I fracture can often be treated with close observation. However, type II and III injury patterns should be evaluated for operative intervention. Transnasal wiring is an effective method to prevent traumatic telecanthus deformity in type III fracture patterns.
Population Pharmacokinetics and Dosing Optimization of Linezolid in Pediatric Patients

Linezolid is a synthetic antibiotic very effective in the treatment of infections caused by Gram-positive pathogens. Although the clinical application of linezolid in children has increased progressively, data on linezolid pharmacokinetics in pediatric patients are very limited. ABSTRACT Linezolid is a synthetic antibiotic very effective in the treatment of infections caused by Gram-positive pathogens. Although the clinical application of linezolid in children has increased progressively, data on linezolid pharmacokinetics in pediatric patients are very limited. The aim of this study was to develop a population pharmacokinetic model for linezolid in children and optimize the dosing strategy in order to improve therapeutic efficacy. We performed a prospective pharmacokinetic study of pediatric patients aged 0 to 12 years. The population pharmacokinetic model was developed using the NONMEM program. Goodness-of-fit plots, nonparametric bootstrap analysis, normalized prediction distribution errors, and a visual predictive check were employed to evaluate the final model. The dosing regimen was optimized based on the final model. The pharmacokinetic data from 112 pediatric patients ages 0.03 to 11.9 years were analyzed. The pharmacokinetics could best be described by a one-compartment model with first-order elimination along with body weight and the estimated glomerular filtration rate as significant covariates. Simulations demonstrated that the currently approved dosage of 10 mg/kg of body weight every 8 h (q8h) would lead to a high risk of underdosing for children in the presence of bacteria with MICs of ≥2 mg/liter. To reach the pharmacokinetic target, an elevated dosage of 15 or 20 mg/kg q8h may be required for them. The population pharmacokinetics of linezolid were characterized in pediatric patients, and simulations provide an evidence-based approach for linezolid dosage individualization.
Managing the middle: A shift in conservation priorities based on the global human modification gradient

An increasing number of international initiatives aim to reconcile development with conservation. Crucial to successful implementation of these initiatives is a comprehensive understanding of the current ecological condition of landscapes and their spatial distributions. Here, we provide a cumulative measure of human modification of terrestrial lands based on modeling the physical extents of 13 anthropogenic stressors and their estimated impacts using spatially explicit global datasets with a median year of 2016. We quantified the degree of land modification and the amount and spatial configuration of low modified lands (i.e., natural areas relatively free from human alteration) across all ecoregions and biomes. We identified that fewer unmodified lands remain than previously reported and that most of the world is in a state of intermediate modification, with 52% of ecoregions classified as moderately modified. Given that these moderately modified ecoregions fall within critical land use thresholds, we propose that they warrant elevated attention and require proactive spatial planning to maintain biodiversity and ecosystem function before important environmental values are lost.