Miracle-dz/UniFAR-FTUs huggingface dataset:
Population pharmacokinetics and pharmacogenomics of tacrolimus in Chinese children receiving a liver transplant: initial dose recommendation

Background In order to improve the precision of treatment with tacrolimus in Chinese patients undergoing pediatric liver transplantation, the optimum initial dose of tacrolimus was determined based on population pharmacokinetics and pharmacogenomics. Methods Demographic data, clinical parameters, drug combinations and pharmacogenomics were integrated to build a population pharmacokinetic model using NONMEM. Additionally, Monte Carlo simulations were used to optimize the recommended initial dose. Results Weight, patient cytochrome 450 3A (CYP3A)5 genotype, and co-administration with wuzhi-capsule (WZ) were incorporated into the final model. For children with a CYP3A5*3/*3 genotype not co-administered WZ, 0.10 mg/kg/day split into two doses was recommended for patients weighing 5–17 kg, and 0.05 mg/kg/day split into two doses was recommended for patients weighing 17–60 kg. For children with a CYP3A5*1 allele not co-administered WZ, 0.25 mg/kg/day for patients weighing 5–10 kg, 0.20 mg/kg/day for patients weighing 10–17 kg, 0.15 mg/kg/day for patients weighing 17–36 kg, and 0.10 mg/kg/day for patients weighing 36–60 kg; all split into two doses was recommended. For children with a CYP3A5*3/*3 genotype co-administered WZ, 0.10 mg/kg/day for patients weighing 5–11 kg, and 0.05 mg/kg/day for patients weighing 11–60 kg; both split into two doses was recommended. For children with a CYP3A5*1 allele who were co-administered WZ, 0.20 mg/kg/day for patients weighing 5–10 kg, 0.15 mg/kg/day for patients weighing 10–22 kg, and 0.10 mg/kg/day for patients weighing 22–60 kg all split into two doses was recommended. Conclusions The optimal initial dose of tacrolimus was determined based on population pharmacokinetics and pharmacogenomics in Chinese patients undergoing pediatric liver transplantation.
In vitro SAFETY EVALUATION OF PALM TOCOTRIENOL-RICH FRACTION NANOEMULSION FOR TOPICAL APPLICATION

The application of nanotechnologies in cosmetics industry has resulted in the introduction of new nanomaterials for topical applications. Nanomaterial overcomes issues of limited penetration and low bioavailability of non-soluble bioactive agents. While there are many advantages of using nanomaterials, recent development in using submicron particles for enhance skin penetration has raised the concern of safety including the increase potential to induce skin irritation and allergic reactions on the skin. The studies on irritation potential of palm tocotrienol-rich fraction (TRF) nanoemulsion using in vitro ocular and dermal irritection assays, reconstructed human epidermis and human corneal epithelium tests were investigated. Palm TRF nanoemulsion did not exhibit any potential skin irritation in the in vitro ocular and dermal irritation assessment. The studies showed that when reconstructed human corneal epithelium and human epidermis models were treated with the tocotrienol macroemulsion and nanoemulsions, no indication of irritancy to the eyes or dermal tissues were observed giving a mean tissue viability of more than 60% and 50%, respectively. The non-irritant category is classified as Category 1 according to United Nations Globally Harmonised System of Classification and Labelling of Chemicals. In vitro studies showed no ocular or dermal irritation potential indicating possible topical application of palm TRF nanoemulsion.
Making city-bases: homeless places, poverty management, and urban change in Pilsen, Czechia

ABSTRACT The article explores how homeless people make places in the public space, while revealing some of the overlooked effects these places may have on the wider city. The article relies on extensive ethnographic research and media coverage analysis of a place called Eskalátory (the Escalators) in Pilsen, a second-order city in Czechia. Eskalátory is part of an underpass with a four-lane road, a tramway, and four outdoor escalators, altogether, forming a specific urban assemblage. The paper describes three specific assemblage enactments of poverty management, homeless placemaking, and socio-materiality, and argues the place played a crucial role in urban change involving the surrounding area. Therefore, it conceptualizes Eskalátory as a “city-base”, an assemblage produced by actors human and non-human that contributes to urban outcome.
Entrepreneurship indicators, policies and their influence on the business environment in West Africa

Background: This article examined the performance of entrepreneurship indicators and their influence on the business environments through economic rankings in selected Anglophone and Francophone countries in West Africa. Aim: An institutional framework for entrepreneurship indicators was adopted as a measure for entrepreneurship in the region focusing on its determinants, impacts and outcomes. Setting: The colonial policy of indirect rule in the Anglophone West Africa focused on economic development and national integration, while the colonial policy of assimilation in the francophone focused on trade and centralisation. Method: This study focused on a comparative evaluation and synthesis. Results: The study found that the Anglophone countries were more entrepreneurship enhancing than the Francophone divide, but the economies in the region were all factor driven. Conclusion: The study recommends private sector partnership in the drive to promote entrepreneurship so that the entrepreneurship drive in the countries aim towards innovative and efficient competitiveness.
Mental Health Issues of International Mainland Chinese College Students in Thailand

This study extends previous research by examining the mental health issues of international mainland Chinese college students in Thailand. The research specifically proposed that mental health issues originate from the relationship between life adaptation and mental health disorders, and this study was conducted to test this assertion. Nine hundred international mainland Chinese college students in Thailand participated in an online survey. The results showed that life adaptation in respect of family relationships, interpersonal relationships, emotions, and learning had a positive effect on mental health disorders and that female and junior students who stayed in Thailand for 1 to 2 years were likely to have significant mental health issues.
Reformed Theology in Modern Europe (Nineteenth and Twentieth Centuries)

The history of nineteenth- and twentieth-century Europe is one of upheaval. How did modern European Reformed theologians and theologies fare as the social, political, cultural, and intellectual ground upon which they stood was shifting? This chapter explores developments in Reformed theology in Scotland, Germany, the Netherlands, Switzerland, France, and Hungary. It argues that the nineteenth century saw Reformed theology coming to terms with the Enlightenment—conforming to it, in the case of classical liberal theology, and challenging it, in the case of the Réveil. In the twentieth century, the two most historically important attempts to reimagine the Reformed faith in a culturally modern Europe were neo-Calvinism (Bavinck and Kuyper) and neo-Orthodoxy (Barth). The story of twentieth-century European Reformed theology, for the most part, was the story of Reformed theologians reorienting themselves in relation to Basel and Amsterdam, as the ground moved beneath their feet.
Twenty years of European mountain permafrost dynamics—the PACE legacy

This paper reviews and analyses the past 20 years of change and variability of European mountain permafrost in response to climate change based on time series of ground temperatures along a south–north transect of deep boreholes from Sierra Nevada in Spain (37°N) to Svalbard (78°N), established between 1998 and 2000 during the EU-funded PACE (Permafrost and Climate in Europe) project. In Sierra Nevada (at the Veleta Peak), no permafrost is encountered. All other boreholes are drilled in permafrost. Results show that permafrost warmed at all sites down to depths of 50 m or more. The warming at a 20 m depth varied between 1.5 °C on Svalbard and 0.4 °C in the Alps. Warming rates tend to be less pronounced in the warm permafrost boreholes, which is partly due to latent heat effects at more ice-rich sites with ground temperatures close to 0 °C. At most sites, the air temperature at 2 m height showed a smaller increase than the near-ground-surface temperature, leading to an increase of surface offsets (SOs). The active layer thickness (ALT) increased at all sites between c. 10% and 200% with respect to the start of the study period, with the largest changes observed in the European Alps. Multi-temporal electrical resistivity tomography (ERT) carried out at six sites showed a decrease in electrical resistivity, independently supporting our conclusion of ground ice degradation and higher unfrozen water content.
The effects of sound therapy in tinnitus are characterized by altered limbic and auditory networks

Abstract To determine the neural mechanism underlying the effects of sound therapy on tinnitus, we hypothesize that sound therapy may be effective by modulating both local neural activity and functional connectivity that is associated with auditory perception, auditory information storage or emotional processing. In this prospective observational study, 30 tinnitus patients underwent resting-state functional magnetic resonance imaging scans at baseline and after 12 weeks of sound therapy. Thirty-two age- and gender-matched healthy controls also underwent two scans over a 12-week interval; 30 of these healthy controls were enrolled for data analysis. The amplitude of low-frequency fluctuation was analysed, and seed-based functional connectivity measures were shown to significantly alter spontaneous local brain activity and its connections to other brain regions. Interaction effects between the two groups and the two scans in local neural activity as assessed by the amplitude of low-frequency fluctuation were observed in the left parahippocampal gyrus and the right Heschl's gyrus. Importantly, local functional activity in the left parahippocampal gyrus in the patient group was significantly higher than that in the healthy controls at baseline and was reduced to relatively normal levels after treatment. Conversely, activity in the right Heschl's gyrus was significantly increased and extended beyond a relatively normal range after sound therapy. These changes were found to be positively correlated with tinnitus relief. The functional connectivity between the left parahippocampal gyrus and the cingulate cortex was higher in tinnitus patients after treatment. The alterations of local activity and functional connectivity in the left parahippocampal gyrus and right Heschl’s gyrus were associated with tinnitus relief. Resting-state functional magnetic resonance imaging can provide functional information to explain and ‘visualize’ the mechanism underlying the effect of sound therapy on the brain.
Identifying the Externally Forced Atlantic Multidecadal Variability Signal Through Florida Rainfall

The North Atlantic experiences basin‐wide, multidecadal changes in sea surface temperature (SST), and this SST variability is linked with regional‐to‐continental scale impacts. These impacts often serve as motivation to study the underlying contributors to Atlantic Multidecadal Variability (AMV). However, these impacts can be more than motivation—they can be tools to study the AMV itself. Herein, we consider the positive correlation between Florida summertime rainfall and the AMV (Enfield et al., 2001, https://doi.org/10.1029/2000GL012745). First, we show that this relationship is apparent in updated observational data sets. Next, we demonstrate that large ensembles of climate models are capable of producing the observed relationship between the AMV and Florida summertime rainfall. Finally, using large ensembles from multiple climate models, we show that historical forcing makes models more likely to capture the observed relationship in summer precipitation. Our findings have implications for our understanding of the AMV and for precipitation projections in at‐risk South Florida.
Revision of the Synechococcales (Cyanobacteria) through recognition of four families including Oculatellaceae fam. nov. and Trichocoleaceae fam. nov. and six new genera containing 14 species

A total of 48 strains of thin, filamentous cyanobacteria in Synechococcales were studied by sequencing 16S rRNA and rpoC1 sequence fragments. We also carefully characterized a subset of these by morphology. Phylogenetic analysis of the 16S rRNA gene data using Bayesian inference of a large Synechococcales alignment (345 OTU’s) was in agreement with the phylogeny based on the rpoC1 gene for 59 OTU’s. Both indicated that the large family-level grouping formerly classified as the Leptolyngbyaceae could be further divided into four family-level clades. Two of these family-level clades have been recognized previously as Leptolyngbyaceae and Prochlorotrichaceae. Oculatellaceae fam. nov. and Trichocoleaceae fam. nov. are proposed for the other two families. The Oculatellaceae was studied in greater detail, and six new genera containing 14 species were characterized and named. These new taxa are: Pegethrix botrychoides, P. olivacea, P. convoluta, P. indistincta, Drouetiella lurida, D. hepatica, D. fasciculata, Cartusia fontana, Tildeniella torsiva, T. nuda, Komarkovaea angustata, Kaiparowitsia implicata, Timaviella obliquedivisa, and T. radians.
Delayed Age at First Breeding and Experimental Removals Show Large Non-Breeding Surplus in Pied Flycatchers

Avian breeding populations have been shown to be regulated by territorial behaviour, often creating a surplus of non-breeding individuals. However, most evidence is of a male non-breeder surplus, whereas for a surplus to actually buffer a population both non-breeding males and females should be present. Here, we provide descriptive and experimental evidence for the existence of a population buffer consisting of mostly male and potentially also female Pied Flycatchers using nest box areas. First we show that local recruits often do not breed in their first year, with 23% of all recruiting males observed breeding in their first year, and 51% of females. When accounting for mortality in the years prior to observed first breeding, we estimate that only 9% of all first-year males breed locally, and 29% of first-year females. Similar percentages of first-year flycatchers skipping breeding have been observed in other study populations. We show that in the year of new establishment of our nest box plots, most known-aged flycatchers were first-year birds (77%), whereas after establishment, recruiting immigrants from the same source population were mostly older (28% first-year birds). An experimental removal of paired flycatchers from one study plot in two years (19 and 58 individuals removed) resulted in complete replacement by males and females. Male but not female replacements were younger than removed individuals. These results imply that a non-breeding surplus is present in Pied Flycatcher populations. The average later age at first-breeding in males compared to females, suggests that this non-breeding surplus is strongly male-biased. Skipping breeding in the first year(s) is not just caused by shortage of suitable nesting sites, as we observed on average 12% of males defending a nest box without pairing up with a female. Using stable isotopes ratios, we show that non-breeding first-year individuals do not stay at their African wintering grounds. Competition for nest sites is one cause for refraining from breeding, as shown by our experiments, but cannot be the sole cause, as many nest boxes remain unused in a season, and up to 20% of territorial males defend a nest box without pairing up with a female. We hypothesize that many young flycatchers arrive too late for breeding and are therefore not seen in their first year. Indeed first-year Pied Flycatchers that do breed/defend a nest box arrive on average later at the breeding grounds, and we argue that the non-observed group arrives even later. The causes of their later arrival could be the need for learning, lower quality wintering sites resulting in later departure, and/or a trade-off between low breeding success and the costs of early arrival. These could be general factors in long-distance migrants, and this pleads for a better understanding of how migration develops during ontogeny.
Climate change increases ecogeographical isolation between closely related plants

Ecogeographical isolation is a fundamental prezygotic barrier to reproduction and a step towards diversification in flowering plants. However, whether ecogeographical isolation acts as a reproductive barrier between species and thus as a mechanism for species divergence is unclear and is expected to change as species distributions shift under climate change. Using a Maxent framework, we quantified the extent of ecogeographical isolation of nine closely related species of the European plant genus Pulmonaria, which lack premating barriers and often form hybrids. We investigated ecogeographical isolation under both current conditions and four climate change scenarios; two unrelated future climate models, each with two predictions of the potential trajectories of climate change. Compared with current climates, under these future climate scenarios, there will be an increase in mean annual temperature, but not in mean annual precipitation in the range of Pulmonaria throughout Europe. This will result in a range contraction in three of the nine Pulmonaria species, a range expansion in two species, and no clear effect of climate change on the ranges of four species. Climate change will result in an overall increase in ecogeographical isolation between these species in future. In particular, species that have low ecogeographical isolation under current conditions are predicted to increase the most in their ecogeographical isolation under climate change. Synthesis. These results highlight that climate change can strongly impact on a major premating barrier of closely related species, therefore potentially affect the evolutionary trajectory of plants in the future.
The perceived influence of the one-on-one instrumental learning environment on tertiary string students’ perceptions of their own playing-related discomfort/pain

Abstract This article draws on qualitative data collected over a five-year period as part of a longitudinal mixed methods research project at a tertiary music institution in Australia. Forty tertiary string students consistently identified factors specific to the one-on-one instrumental teaching environment as influencing their perceptions as to the nature and causes of their playing-related discomfort pain. Student perceptions of individual teacher’s attitudes to pain and injury, experiences with regards to asking and receiving advice and the perceived influence of the first instrumental teacher are discussed using six examples. The paper concludes with several recommendations for instrumental music teachers and music institutions.
A search for variable subdwarf B stars in TESS full frame images – I. Variable objects in the southern ecliptic hemisphere

We report the results of our search for pulsating subdwarf B stars in Full Frame Images, sampled at 30 min cadence and collected during Year 1 of the TESS mission. Year 1 covers most of the southern ecliptic hemisphere. The sample of objects we checked for pulsations was selected from a subdwarf B stars database available to public. Only two positive detections have been achieved, however, as a by-product of our search we found 1807 variable objects, most of them not classified, hence their specific variability class cannot be confirmed at this stage. Our preliminary discoveries include: two new subdwarf B (sdB) pulsators, 26 variables with known sdB spectra, 83 non-classified pulsating stars, 83 eclipsing binaries (detached and semi-detached), a mix of 1535 pulsators and non-eclipsing binaries, two novae, and 77 variables with known (non-sdB) spectral classification. Among eclipsing binaries we identified two known HW Vir systems and four new candidates. The amplitude spectra of the two sdB pulsators are not rich in modes, but we derive estimates of the modal degree for one of them. In addition, we selected five sdBV candidates for mode identification among 83 pulsators and describe our results based on this preliminary analysis. Further progress will require spectral classification of the newly discovered variable stars, which hopefully include more subdwarf B stars.
Polyploidy in Animal Development and Disease

Somatic polyploidization is a developmentally controlled process that can be found in many animal species, including mammals. Polyploidy is utilized as a mechanism to amplify gene expression via an increase in DNA copy number, to drive cellular growth, and to initiate cellular differentiation. Moreover, polyploidy has been implicated in the response to injury or disease. This chapter discusses the processes by which polyploid cells arise and the underlying molecular mechanisms, with a focus on endoreplication in Drosophila and mice. In addition, it summarizes recent progress on the related subjects of endomitosis, ploidy reversal, and gene amplification.
The CDC and State Health Department Facebook Messages: An Examination of Frames and the Extended Parallel Processing Model

ABSTRACT Public health organizations such as the Centers for Disease Control and Prevention (CDC) and state and local health departments are increasingly using social media in health education and promotion. Guided by the Extended Parallel Processing Model and framing theory, this study analyzed the Facebook messages of both the CDC and state health departments in 2017 to examine the extent to which such messages used these theories of social influence. All messages posted by the CDC in 2017 were downloaded. A multi-stage random sampling method was used to identify state-level health departments’ posts. Differences were found in the CDC and state health organizations’ Facebook messages in terms of the four EPPM variables. The CDC’s Facebook posts were more likely to include severity, susceptibility, self-efficacy, and response efficacy than those posted by state health departments. In addition, while the state health departments were more likely to use gain frames, the CDC was more likely to use both gain and loss frames simultaneously.