Miracle-dz/UniFAR-FTUs huggingface dataset:
Relative bioavailability and pharmacokinetic comparison of a fixed‐dose combination tablet of mosapride, pancreatin, and simethicone relative to single‐component mosapride tablets in healthy Mexican subjects

Abbott Laboratories de México S.A. de C.V. developed a new fixed‐dose combination of mosapride 5 mg, pancreatin 170 mg, and simethicone 125 mg as an alternative to the mosapride monotherapy to improve overall satisfaction and adequate relief of gastrointestinal disorders symptoms and to reduce multiple pill burden. As a part of the fixed‐dose combination registration process in Mexico, a pharmacokinetic and relative bioavailability study was carried out to demonstrate nonexistence of pharmacokinetic interaction when mosapride is administered alone or in combination with pancreatin and simethicone using DOSIER® (mosapride) 5‐mg tablets as a reference product. Tolerability of the fixed‐dose combination tablet was assessed. In this open‐label, randomized, oral single‐dose, two‐way crossover study, 65 healthy male and female subjects received either the fixed‐dose combination tablet or the reference product during each study period. The two study periods were separated by a 7‐day washout period. Mosapride concentrations in plasma samples were determined using a validated ultra‐performance liquid chromatography coupled with tandem mass spectrometry (UPLC‐MS/MS) method. Blood samples were collected for up to 16 h post dose. The primary evaluation criteria were Cmax and AUC0–t for mosapride. The 90% confidence intervals for the ratio of geometric means for Cmax (96.12% to 110.90%) and AUC0–t (99.07% to 108.06%) were within the defined acceptance limits of 75% to 133% and 80% to 125% for Cmax and AUC0–t, respectively, indicating bioequivalence between the two products. Both products were safe and well tolerated. Therefore, mosapride in combination with pancreatin and simethicone tablet is bioequivalent to mosapride alone, and no new safety signals emerged.
Nitrate‐inducible MdBT2 acts as a restriction factor to limit apple necrotic mosaic virus genome replication in Malus domestica

Abstract Apple necrotic mosaic virus (ApNMV) is highly associated with the occurrence of apple mosaic disease in China. However, ApNMV–host interactions and defence mechanisms of host plants against this virus are poorly studied. Here, we report that nitrate treatment restrains ApNMV genomic RNA accumulation by destabilizing viral replication protein 1a through the MdBT2‐mediated ubiquitin‐proteasome pathway. MdBT2, a nitrate‐responsive BTB/TAZ domain‐containing protein, was identified in a yeast two‐hybrid screen of an apple cDNA library using viral protein 1a as bait, and 1a was further confirmed to interact with MdBT2 both in vivo and in vitro. It was further verified that MdBT2 promoted the ubiquitination and degradation of viral protein 1a through the ubiquitin‐proteasome pathway in an MdCUL3A‐independent manner. Viral genomic RNA accumulation was reduced in MdBT2‐overexpressing transgenic apple leaves but enhanced in MdBT2‐antisense leaves compared to the wild type. Moreover, MdBT2 was found to interfere with the interaction between viral replication proteins 1a and 2apol by competitively interacting with 1a. Taken together, our results demonstrate that nitrate‐inducible MdBT2 functions as a limiting factor in ApNMV viral RNA accumulation by promoting the ubiquitination and degradation of viral protein 1a and interfering with interactions between viral replication proteins.
IMPROVED ESTIMATION OF FLOOR SPECTRA IN RC WALL BUILDINGS

Adequate seismic design of non-structural elements can only be guaranteed if floor seismic demands can be appropriately quantified. To this extent, most international codes currently suggest an equivalent static method where the seismic force acting on a component is computed as a function of the component mass and the peak acceleration that the component experiences throughout the seismic event. However, recent studies have shown that current code approaches are, in most cases, unreliable as they do not adequately address important aspects related to the properties of the elements to be designed as well as characteristics of the supporting structure. This work examines floor accelerations and acceleration response spectra for a 20-storey case study structure consisting of a RC wall system, subjected to a set of ground motions scaled to various levels of intensity. Firstly, the shortcomings of international code approaches are highlighted, showing that floor spectra and peak floor accelerations are generally poorly predicted even for linear supporting systems. Secondly, a discussion of the factors that affect the peak floor accelerations as well as the shape and intensity of acceleration demands on secondary structural and non-structural elements is presented. A new method that addresses aspects such as damping of the secondary system as well as effects of non-linearity and higher modes relative to the primary structure is then reviewed. Finally, the performance of the proposed procedure to estimate acceleration floor spectra is investigated by comparing predicted spectra with those obtained from time-history analyses of the case study building. The results of the research indicate that the newly proposed methodology is very promising, providing considerably improved prediction of floor spectra compared to existing code methods and should therefore be developed further as part of future research.
Counting Motorcycles and Estimating Motorcycle Vehicle Miles of Travel

Recent increases in motorcycle fatalities, in the rate of motorcycle fatalities per vehicle mile of travel (VMT), and in the ratio of estimated motorcycle VMT to motorcycle registrations have resulted in greater attention to motorcycle safety and to related motorcycle statistics. Technologies that are currently used for collecting counts of vehicles by vehicle class or that have been proposed for use in counting motorcycles are reviewed. Available information about the quality of motorcycle counts produced by these technologies is discussed. Several recommendations for improving the quality of motorcycle counts and count-based VMT estimates for Class 1 vehicles are included. Also discussed are some factors that are likely to have contributed to the observed divergence between the growth rates of motorcycle registrations and those of motorcycle VMT estimates. The use of registration or insurance company data, or both, for estimating VMT of these vehicles without the use of count data is briefly discussed.
Global Scientific Research on SARS-CoV-2 Vaccines: A Bibliometric Analysis

Objective We performed this bibliometric analysis to identify global scientific research on the SARS-CoV-2 vaccines. Materials and Methods This bibliometric analysis study inclusive search of English-language publications related to the SARS-CoV-2 vaccines was conducted in the Scopus, PubMed, and Dimensions databases without year limitations. The results of bibliometric analysis comprised a time-dependent citation density trend, the name of the journal, journal impact factor (IF), year of publication, type of article, category, subscription or affiliation, co-authorship, and co- occurrence network. Results A study of the scientific literature from three databases (Scopus, PubMed, Dimensions) shows that investigators have focused more on studying the structure of the coronavirus at different levels (organismic, cellular, and molecular). In addition, the method of virus penetration into the cell and features of the influence of coronavirus on animals are well-studied. Various methods and strategies are being used to develop the vaccines, including both animal-tested methods and computer models. The Dimensions database is the most representative in terms of coverage of research on development of the SARS-CoV-2 vaccines. Conclusion This research is a scientific investigation based on bibliometric analysis of papers related to the SARS-CoV-2 vaccines. The Dimensions database provides the most representative research coverage on the creation of a vaccine against coronavirus. It is characterized by a large number of formed verbose terms (length of more than four words) related to coronavirus, which makes it possible to track trends in the development of methods for creating a vaccine.
Transposable elements mark a repeat‐rich region associated with migratory phenotypes of willow warblers (Phylloscopus trochilus)

The genetic basis of bird migration has been the focus of several studies. Two willow warbler subspecies (Phylloscopus trochilus trochilus and Phylloscopus trochilus acredula) follow different migratory routes to wintering grounds in Africa. Their breeding populations overlap in contact areas or “migratory divides” located in central Scandinavia and in eastern Poland. Earlier analyses demonstrated that the genetic differences between these two migratory phenotypes are few and cluster on chromosomes 1 and 5. In addition, an amplified fragment length polymorphism‐derived biallelic marker (known as WW2) presents steep clines across both migratory divides but failed to be mapped in the genome. Here, we characterize the WW2 marker and describe its two variants (WW2 ancestral and WW2 derived) as portions of long terminal repeat retrotransposons originating from an ancient infection by an endogenous retrovirus. We used quantitative polymerase chain reaction techniques to quantify copy numbers of the WW2 derived variant in the two subspecies and their hybrids. This, together with genome analyses revealed that WW2 derived variants are much more abundant in P. t. acredula and appear embedded in a large repeat‐rich region (>12 Mbp), not associated with the divergent regions of chromosomes 1 or 5. However, it might interact with genetic elements controlling migration direction. Testing this hypothesis further will require knowing the exact location of this region, such as by obtaining more complete genome assemblies preferably in combination with techniques like fluorescence in situ hybridization applied to a willow warbler karyotype, and finally to investigate the copy number of this marker in hybrids with known migratory tracks.
Socio-demographic and familial factors associated with hospital admissions and repeat admission for dental caries in early childhood: A population-based study.

OBJECTIVES Dental caries remains a complex childhood condition often requiring preventable hospital admissions. There are limited population-based epidemiological studies that use large and linked data sets to quantify the clinical, socio-demographic and familial risk factors related to hospital admissions for dental caries. The aim of this study was to describe and quantify the rates, socio-demographic, clinical characteristics and familial factors including repeat admissions associated with young children admitted to hospital for dental caries. METHODS This cohort study (n = 33,438) used longitudinally linked hospital admission data among all children aged <six years in NSW, Australia. Socio-demographic and admission characteristics of children and those with one versus two or more admissions for dental caries were compared. Familial risk factors were analysed for a restricted cohort of families with two or more children (n = 18,174) using multivariable logistic regression to assess the familial factors associated with multiple hospital admissions for dental caries adjusting for other socio-demographic characteristics. RESULTS There were 33,438 children aged <six years who had 34,446 hospital admissions for dental caries between 2001 and 2014. The annual rate of 4.3 per 1000 children remained unchanged over the period. Most admissions required general anaesthesia (96%), and 8.4% of children had repeat admissions. Children living in disadvantaged or in regional and rural areas attending public hospitals were more likely to have dental extractions during the admission. Children from the same family had a 2.7-fold increased odds of admission if the first child admitted was less than three years of age (adjusted odd ratio 2.69; 95% CI: 2.36-3.07), a 1.5 fold increase for socioeconomic disadvantage (aOR 1.45; 1.19 - 1.77) and a 1.9 fold increase of admission if the family had 4 or more children (aOR1.88; 1.47 - 2.42). CONCLUSIONS Findings highlight socio-demographic inequities associated with hospital admission for dental caries. The provision of targeted dental care programs for 'at-risk' families should address these inequalities and presents an opportunity to reduce dental caries related hospitalizations.
A case study in forensic soil comparison

Soil examination can provide useful forensic information about the spatial location and suspect's activities. Many techniques have been applied for soil comparison and provenance determination in criminal investigations. Pollen and diatom identification, which has the potential to provide an independent ecological assessment of soil evidence, is currently underused in forensic soil analysis. This work presents a case study of application of these methods to help criminal investigation in a murder case, which happened in an irrigation ditch in Hunan Province, southern China. Soils from the suspect's clothes, the exact crime scene spot in the irrigation ditch, along the ditch and the reference ditches were collected and analyzed. In addition to the element and mineral analysis, pollen and diatom assemblages were analyzed for further comparison. The statistical methods of hierarchical cluster and cosine similarity analysis were carried out to assist in soil comparison and provenance determination. The results showed that soil on the suspect's clothes had a high probability to share the same source with the soil from the crime scene in the irrigation ditch. The suspect confessed to murder based largely on the soil examination result even without other evidences.
Application of a physiologically based pharmacokinetic model of rivaroxaban to prospective simulations of drug–drug–disease interactions with protein kinase inhibitors in cancer‐associated venous thromboembolism

Rivaroxaban is a viable anticoagulant for the management of cancer‐associated venous thromboembolism (CA‐VTE). A previously verified physiologically‐based pharmacokinetic (PBPK) model of rivaroxaban established how its multiple pathways of elimination via both CYP3A4/2J2‐mediated hepatic metabolism and organic anion transporter 3 (OAT3)/P‐glycoprotein‐mediated renal secretion predisposes rivaroxaban to drug–drug–disease interactions (DDDIs) with clinically relevant protein kinase inhibitors (PKIs). We proposed the application of PBPK modelling to prospectively interrogate clinically significant DDIs between rivaroxaban and PKIs (erlotinib and nilotinib) for dose adjustments in CA‐VTE.
Return of the lysergamides. Part VII: Analytical and behavioural characterization of 1-valeroyl-d-lysergic acid diethylamide (1V-LSD).

The psychopharmacological properties of the psychedelic drug lysergic acid diethylamide (LSD) have attracted the interest of several generations of scientists. Whilst further explorations involving novel LSD-type compounds are needed to assess their potential as medicinal drugs, the emergence of novel derivatives as recreational drugs has also been observed. 1-Valeroyl-LSD (also known as 1-valeryl-LSD, 1-pentanoyl-LSD, 1V-LSD, or "Valerie") is a new N1 -acylated LSD derivative that recently appeared on the online market and it could be viewed as a higher homolog of ALD-52, 1P-LSD, and 1B-LSD. The present study included the analytical characterization and involved various methods of mass spectrometry (MS), gas- and liquid chromatography (GC and LC), nuclear magnetic resonance spectroscopy (NMR), GC solid-state infrared (GC-sIR) analysis and Raman spectroscopy. The in vivo activity of 1V-LSD was assessed using the mouse head twitch response (HTR), a 5-HT2A -mediated head movement that serves as a behavioral proxy in rodents for human hallucinogenic effects. Similar to LSD and other psychedelic drugs, the HTR induced by 1V-LSD was dose-dependent and the median effective dose for 1V-LSD was 373 nmol/kg, which was about a third of the potency of LSD (ED50 = 132.8 nmol/kg). Lysergamides containing the N1 -substituent typically act as weak partial agonists at the 5-HT2A receptor and are believed to serve as prodrugs for LSD. 1V-LSD is also likely to be hydrolyzed to LSD and serve as a prodrug, but studies to assess the biotransformation and receptor pharmacology of 1V-LSD should be performed to fully elucidate its mechanism-of-action.
Pulse‐to‐pulse correlation in satellite radar altimeters

Pulse-to-pulse correlation in satellite radar altimeters is examined to determine if range jitter in future altimeters could be reduced by increasing the pulse repetition frequency (PRF). Data from the Skylab radar altimeter is analyzed and compared with rules of thumb and the results of a Monte Carlo simulation. Altimeter range tracker configurations are reviewed and a simple curve is developed for the PRF below which decorrelation is assured. An adaptive PRF for future altimeters is recommended to conserve mission power while optimizing data collection during high-sea states.
Toll-Like Receptor 4: A Macrophage Cell Surface Receptor Is Activated by Trimethylamine-N-Oxide

Objective Trimethylamine-N-Oxide (TMAO) is considered as a risk factor for atherosclerosis which further leads to inflammation during atherosclerosis. The exact mechanism(s) by which TMAO induces the inflammatory reactions remains to be determined. TMAO can cause the endoplasmic reticulum (ER) stress that triggers activation of Toll-Like Receptors (TLRs). In macrophages, this process stimulates the production of proinflammatory cytokines. This study designed to evaluate the expression level of TLR4 in TMAO-treated macrophages. Materials and Methods In this experimental study, different concentrations of TMAO (37.5, 75, 150, and 300 μM) were exposed to murine macrophage (J774A.1 cell line) for 8, 18, 24, and 48 hours. The cells were also treated with 2.5 mM of 4-phenyl butyric acid as well as 2µg/ml of tunicamycin respectively as negative and positive controls for inducing ER-stress. We measured the viability of treated cells by the MTT test. Besides, the expression levels of TLR4 gene and protein were evaluated using western blotting and reverse transcription- quantitative polymerase chain reaction (RT-qPCR) analysis. One-Way ANOVA was used for statistical analysis. Results No cell death was observed in treated cells. The cells treated with 150 and 300 μM doses of TMAO for 24 hours showed a significant elevation in the protein and/or mRNA levels of TLR4 when compared to normal control or tunicamycin-treated cells. Conclusion Our results may in part elucidate the mechanism by which TMAO induces the macrophage inflammatory reactions in response to the induction of ER stress, similar to what happens during atherosclerosis. It also provides documentation to support the direct contribution of TLR4 in TMAO-induced inflammation.
Nodulating white lupins take advantage of the reciprocal interplay between N and P nutritional responses

Abstract The low bioavailability of nutrients, especially nitrogen (N) and phosphorus (P), is one of the most limiting factors for crop production. In this study, under N‐ and P‐free nutrient solution (−N−P), nodulating white lupin plants developed some nodules and analogous cluster root structures characterized by different morphological, physiological, and molecular responses than those observed upon single nutrient deficiency (strong acidification of external media, a better nutritional status than −N+P and +N−P plants). The multi‐elemental analysis highlighted that the concentrations of nutrients in white lupin plants were mainly affected by P availability. Gene‐expression analyses provided evidence of interconnections between N and P nutritional pathways that are active to promote N and P balance in plants. The root exudome was mainly characterized by N availability in nutrient solution, and, in particular, the absence of N and P in the nutrient solution triggered a high release of phenolic compounds, nucleosides monophosphate and saponines by roots. These morphological, physiological, and molecular responses result from a close interplay between N and P nutritional pathways. They contribute to the good development of nodulating white lupin plants when grown on N‐ and P‐free media. This study provides evidence that limited N and P availability in the nutrient solution can promote white lupin‐Bradyrhizobium symbiosis, which is favourable for the sustainability of legume production.
Effect of Different Preparation Depths for an Inlay-Retained Fixed Partial Denture on the Accuracy of Different Intraoral Scanners: An In Vitro Study.

PURPOSE The aim was to evaluate the effect of different preparation depths for inlay-retained fixed partial dentures on the accuracy of intraoral scanners. MATERIALS AND METHODS Tooth preparations for two inlay-retained fixed partial dentures were done and divided according to depth of the preparation. Group A: 2mm pulpal floor depth, 3mm gingival floor depth and Group B: 3mm pulpal floor depth, 4mm gingival floor depth. The CEREC Omnicam4.4. 4, Omnicam4.6. 2. Trios3 and Medit i500 intraoral scanners were used in this study. Tooth preparations were scanned by each scanner 10 times. The STL files obtained from the intraoral scanners were compared to the reference models (trueness) and within each test group (precision) using a 3D comparison software. Data were then statistically analyzed. RESULTS Regarding trueness, two-way ANOVA revealed significant differences between the different types of scanners (p<0.001) (Omnicam4.4.4: 65.09 ±2.87 Omnicam4.6.1: 52.73 ±3.31 Medit i500: 58.45 ±2.63 Trios 3: 41.79 ±4.42). Preparation depth had no significant influence on the trueness (p = 0.083). For precision two-way ANOVA revealed significant differences between the different types of scanners (p<0.001). Preparation depth had no significant influence on the precision (p = 0.111). Statistically significant interactions were found between the different variables. CONCLUSIONS The depth of preparation did not have an influence on the accuracy of different scanners. However, the type of scanner influenced the accuracy of digital impressions with Trios3 showing the highest accuracy. This article is protected by copyright. All rights reserved.
Grandmothers are part of the parenting network, too! A longitudinal study on coparenting, maternal sensitivity, child attachment and behavior problems in a Chinese sample

Abstract Grandmothers are important in Chinese families. This study explored the early emerging mother‐grandmother‐infant network and its association with child's socioemotional development in multigenerational families in a non‐WEIRD country. The analytic sample included 60 children (T1: M age = 6.5 months) and their caregivers residing in Beijing. Measures used were the Strange Situation Procedure (SSP), the Lausanne Trilogue Play (LTP), the Maternal Behavior Q‐Sort (MBQS), and the Infant‐Toddler Social and Emotional Assessment. Structural equation and path modeling revealed that (1) more grandmaternal neutral/watching coparenting behaviors at the first assessment were related to more secure infant‐mother attachment relationships at the second assessment (T2: M age = 1 year); (2) maternal sensitivity at T2 was a partial mediator between earlier undermining and neutral/watching coparenting behaviors and young children's externalizing problems at the final assessment (T3: M age = 2 years). Findings are discussed in terms of the roles played by mother‐grandmother coparenting network in the children's socioemotional development.