Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a KLF5-dependent program and drug development for skeletal muscle atrophy

Significance Skeletal muscle atrophy occurs as a result of a variety of conditions including aging, disuse, and cachexia. In this study, we show that the transcription factor KLF5 is transiently up-regulated by metabolic and disuse stimulations and plays a pivotal role in the onset of muscle atrophy in vitro and in vivo. KLF5 physically interacts with Foxo1, and together, they regulate the transcription of Fbxo32, a key atrophy-inducing ubiquitin ligase. A synthetic retinoid, Am80, attenuates muscle atrophy in vitro and in vivo. Moreover, publicly available data sets showed that in humans, KLF5 expression significantly increased with aging and with sarcopenia and correlated positively with expression of the ubiquitin ligase genes FBXO32 and TRIM63. Skeletal muscle atrophy is caused by various conditions, including aging, disuse related to a sedentary lifestyle and lack of physical activity, and cachexia. Our insufficient understanding of the molecular mechanism underlying muscle atrophy limits the targets for the development of effective pharmacologic treatments and preventions. Here, we identified Krüppel-like factor 5 (KLF5), a zinc-finger transcription factor, as a key mediator of the early muscle atrophy program. KLF5 was up-regulated in atrophying myotubes as an early response to dexamethasone or simulated microgravity in vitro. Skeletal muscle–selective deletion of Klf5 significantly attenuated muscle atrophy induced by mechanical unloading in mice. Transcriptome- and genome-wide chromatin accessibility analyses revealed that KLF5 regulates atrophy-related programs, including metabolic changes and E3-ubiquitin ligase-mediated proteolysis, in coordination with Foxo1. The synthetic retinoic acid receptor agonist Am80, a KLF5 inhibitor, suppressed both dexamethasone- and microgravity-induced muscle atrophy in vitro and oral Am80 ameliorated disuse– and dexamethasone-induced atrophy in mice. Moreover, in three independent sets of transcriptomic data from human skeletal muscle, KLF5 expression significantly increased with age and the presence of sarcopenia and correlated positively with the expression of the atrophy-related ubiquitin ligase genes FBXO32 and TRIM63. These findings demonstrate that KLF5 is a key transcriptional regulator mediating muscle atrophy and that pharmacological intervention with Am80 is a potentially preventive treatment.
Metagenome-wide association study revealed disease-specific landscape of the gut microbiome of systemic lupus erythematosus in Japanese

Objective Alteration of the gut microbiome has been linked to the pathogenesis of systemic lupus erythematosus (SLE). However, a comprehensive view of the gut microbiome in SLE and its interaction with the host remains to be revealed. This study aimed to reveal SLE-associated changes in the gut microbiome and its interaction with the host by a comprehensive metagenome-wide association study (MWAS) followed by integrative analysis. Methods We performed a MWAS of SLE based on shotgun sequencing of the gut microbial DNA from Japanese individuals (N case=47, N control=203). We integrated the result of the MWAS with the genome-wide association study (GWAS) data and plasma metabolite data. Results Via species level phylogenetic analysis, we identified and validated increases of Streptococcus intermedius and Streptococcus anginosus in the patients with SLE. Microbial gene analysis revealed increases of Streptococcus-derived genes including one involved in redox reaction. Additionally, microbial pathways related to sulfur metabolism and flagella assembly were altered in the patients with SLE. We identified an overlap in the enriched biological pathways between the metagenome and the germline genome by comparing the result of the MWAS and the GWAS of SLE (ie, MWAS-GWAS interaction). α-diversity and β-diversity analyses provided evidence of dysbiosis in the metagenome of the patients with SLE. Microbiome-metabolome association analysis identified positive dosage correlation of acylcarnitine with Streptococcus intermedius, an SLE-associated taxon. Conclusion Our MWAS followed by integrative analysis revealed SLE-associated changes in the gut microbiome and its interaction with the host, which contribute to our understanding of the relationship between the microbiome and SLE.
Long-term changes in soil properties and microbial 2 communities are continuous cropping obstacles 3 associated with American ginseng ( Panax 4 quinquefolius L . ) cultivation 5

This study aims to verify the time-variant feature of American ginseng (AG) continuous 11 cropping obstacles and to explore the factors impeding continuous cropping. We verified the 12 feature with a plant-soil feedback pot experiment and then investigated the factors by comparing 13 the properties of control soils that had not been previously used for growing ginseng (CS) with those 14 of soils with a 10-year-crop-rotation cycle following the growth of AG (RS). It’s found that the 15 survival rate of AG in RS was lower than that in CS. The RS had lower pH, available potassium 16 content, and urease activity. Additionally, p-coumaric, p-hydroxybenzoic, vanillic, caffeic, and 17 cinnamic acid levels were lower in RS than in CS, but salicylic acid levels showed the opposite 18 pattern. RS had higher Rhodanobacter and lower Acidothermus, Sphingomonas relative abundances in 19 bacterial community. It’s also found that many bacteria were substantially correlated with phenolic 20 acids and soil physiochemical properties. Results indicate that even after 10-year crop rotation, the 21 negative effects of prior continuous cropping of AG has not been eliminated. The growth of AG can 22 be affected negatively with deterioration of soil physicochemical properties and with lower levels 23 of phenolic acids which promote pathogen reproduction. Probiotics reduction also weighs. 24 Moreover, biotic factors are interrelated with abiotic ones. Therefore, it can be inferred that the 25 comprehensive change of soil properties is the main obstacle for continuous cropping. 26
Exploring the role of peer observation of teaching in facilitating cross-institutional professional conversations about teaching and learning

ABSTRACT This paper explores how cross-institutional Peer Observation of Teaching (PoT) provided a stru ctured opportunity for professional conversations by which observers and observees shared and developed their perspectives on teaching experience and skills. Such professional conversations offer opportunities for both parties to gain a perspective on practices that may have been taken for granted. Participants from three Higher Education institutions engaged in cross-disciplinary and cross-institutional PoT, followed by facilitated reflective conversations. This paper captures the factors for success that enabled continuing conversations on teaching and learning and highlights the value of supporting such conversations outside formal, uni-institutional peer observation programmes.
Eulerian‐Lagrangian simulations of settling and agitated dense solid‐liquid suspensions – achieving grid convergence

Submitted to AIChE Journal − July 2017 Revision submitted: October 2017 Accepted: December 2017 Abstract Eulerian-Lagrangian simulations of solid-liquid flo w have been performed. The volume-averaged NavierStokes equations have been solved by a variant of t he la tice-Boltzmann method; the solids dynamics by integrating Newton’s second law for each individual p rticle. Solids and liquid are coupled via mappin g functions. The application is solids suspension in a mixing tank operating in the transitional regime (the impeller-based Reynolds number is 4,000), an overal l solids volume fraction of 10% and a particle-liqu id combination with an Archimedes number of 30. In thi s application, the required grid resolution is dict ated by the liquid flow and we thus need freedom to choo se the particle size independent of the grid spacin g. Preliminary hindered settling simulations show that the proposed Eulerian-Lagrangian mapping strategy indeed offers this independence. The subsequent mix ing tank simulations generate grid-independent results.
Methods for assessing footwear comfort: a systematic review

Abstract Perceived footwear comfort influences wearability and can impact on physical mobility, performance and foot-related complaints. To date, there has been no comprehensive review of the characteristics or methods for measuring perceived footwear comfort. The aims of this systematic review were to identify, appraise and synthesise the literature on methods used to assess perceived footwear comfort, and report their validity and reliability. Electronic databases were systematically searched and the articles screened and appraised for methodological risk of bias using a modified Quality Index checklist. Data on footwear comfort assessment tools (methods, populations, footwear types, reliability/validity) was extracted by two reviewers. A narrative synthesis was undertaken to describe the findings. Ninety-nine articles involving 6980 participants were assessed as eligible for review. Perceived footwear comfort has been assessed by a variety of methods including the visual analogue scale (VAS), Likert-type scales, ranking scales and questionnaires. The studies have covered a range of populations, both healthy and pathological, ranging between ages 8 and 75 years, most commonly adults. Investigations into reliability of perceived footwear comfort scales were limited, and whilst some tools had evidence of moderate to high reliability, findings were population dependent. Developmental or independent validity testing was typically not undertaken. Risk of bias was variable across studies. Perceived footwear comfort assessment has been performed across a wide range of populations and footwear types. Whilst select measures had evidence for their reliability, the results were variable and population dependent. There is scope for further research into the reliability and validity of perceived footwear comfort assessment tools in different populations.
Solving Two Coupled Fuzzy Sylvester Matrix Equations Using Iterative Least-squares Solutions

ABSTRACT In this paper, five iterative methods for solving two coupled fuzzy Sylvester matrix equations are considered. The two coupled fuzzy Sylvester matrix equations are expressed by using the generalized inverse of the coefficient matrix, then iterative solutions are constructed by applying the hierarchical identification principle and by using the block-matrix inner product (the star product for short). A proposed modification to this algorithm to solve the first coupled fuzzy Sylvester matrix equations is suggested. This proposed modification is compared with the first algorithm where our modification exhibits fast convergence behavior. Also, we suggested two least-squares iterative algorithm by applying a hierarchical identification principle to solve the two coupled fuzzy Sylvester matrix equations. The proposed methods are illustrated by numerical examples.
Bullying Victimization and Internalizing Problems of Foreign-Born and U.S.-Born Latino/Hispanic and Asian Adolescents in the United States: The Moderating Role of Parental Monitoring

Objective: Although the association between bullying victimization and internalizing problems is well established, internalizing problems experienced by foreign-born and U.S.-born racial and ethnic minority adolescents in the United States who are victims of bullying are not well understood. This study explores the psychological effects of bullying victimization on foreign-born and U.S.-born Latino/Hispanic and Asian adolescents in the United States and investigates the moderating effects of parental monitoring. Findings may help identify protective factors for bullying victimization. Method: Data were from the 2009–2010 Health Behavior in School-Aged Children study. The study sample comprised 3,349 Latino/Hispanic and 681 Asian American adolescents ages 10–17 from various locations in the United States. Analyses included descriptive statistics, correlation analyses, and hierarchical multivariate regression analyses for foreign-born and U.S.-born adolescents. Results: Foreign-born adolescents were more likely to be bullied than U.S.-born adolescents. For both groups, being bullied increased the likelihood of internalizing problems. Parental monitoring moderated the relationship between bullying victimization and internalizing problems among foreign-born adolescents only. Conclusion: Foreign-born adolescents whose parents monitor their children were less likely to exhibit internalizing problems when bullied. Implications for practitioners working with racial and ethnic minority adolescents in the United States are discussed.
Emerging themes in Population Consequences of Disturbance models

Assessing the non-lethal effects of disturbance from human activities is necessary for wildlife conservation and management. However, linking short-term responses to long-term impacts on individuals and populations is a significant hurdle for evaluating the risks of a proposed activity. The Population Consequences of Disturbance (PCoD) framework conceptually describes how disturbance can lead to changes in population dynamics, and its real-world application has led to a suite of quantitative models that can inform risk assessments. Here, we review PCoD models that forecast the possible consequences of a range of disturbance scenarios for marine mammals. In so doing, we identify common themes and highlight general principles to consider when assessing risk. We find that, when considered holistically, these models provide valuable insights into which contextual factors influence a population's degree of exposure and sensitivity to disturbance. We also discuss model assumptions and limitations, identify data gaps and suggest future research directions to enable PCoD models to better inform risk assessments and conservation and management decisions. The general principles explored can help wildlife managers and practitioners identify and prioritize the populations most vulnerable to disturbance and guide industry in planning activities that avoid or mitigate population-level effects.
Correction to ‘Exact solution to a Liouville equation with Stuart vortex distribution on the surface of a torus’

The constant 8/d in the modified Liouville equation was incorrect. The correct one is 2/d. Hence, the exact solution satisfies the modified Liouville equation, ∇2 TR,r ψ = c edψ + (2/d)κ for c, d ∈ R with cd< 0, where ∇2 TR,r and κ denote the Laplace–Beltrami operator and the Gauss curvature of the toroidal surface TR,r. The results in the original paper are not substantially affected by this correction. In the derivation of the modification term of the Liouville equation in §2, we start with the following ansatz for the exact solution, which was referred to as (2.7) in the original paper:
Modular dynamic biomolecular modelling with bond graphs: the unification of stoichiometry, thermodynamics, kinetics and data

Renewed interest in dynamic simulation models of biomolecular systems has arisen from advances in genome-wide measurement and applications of such models in biotechnology and synthetic biology. In particular, genome-scale models of cellular metabolism beyond the steady state are required in order to represent transient and dynamic regulatory properties of the system. Development of such whole-cell models requires new modelling approaches. Here we propose the energy-based bond graph methodology, which integrates stoichiometric models with thermo-dynamic principles and kinetic modelling. We demonstrate how the bond graph approach intrinsically enforces thermodynamic constraints, provides a modular approach to modelling, and gives a basis for estimation of model parameters leading to dynamic models of biomolecular systems. The approach is illustrated using a well-established stoichiometric model of E. coli and published experimental data.
Revealing problems, pointing fingers, and creating impact A survey of investigative reporters/editors regarding journalistic impact

One measure of success for investigative reporting is impact: Did the story lead to any sort of outcome, from public awareness and dialogue to meaningful policy change? While investigative reporting is historically impact-oriented, there is a dearth of academic scholarship as to what journalists seek and expect when it comes to generating impact. Using data from a national survey of investigative reporters/editors, this research develops a more holistic conceptualization of journalistic impact.
Transfer Reinforcement Learning for Autonomous Driving

Reinforcement learning (RL) is an attractive way to implement high-level decision-making policies for autonomous driving, but learning directly from a real vehicle or a high-fidelity simulator is variously infeasible. We therefore consider the problem of transfer reinforcement learning and study how a policy learned in a simple environment using WiseMove can be transferred to our high-fidelity simulator, WiseMove. WiseMove is a framework to study safety and other aspects of RL for autonomous driving. WiseMove accurately reproduces the dynamics and software stack of our real vehicle. We find that the accurately modelled perception errors in WiseMove contribute the most to the transfer problem. These errors, when even naively modelled in WiseMove, provide an RL policy that performs better in WiseMove than a hand-crafted rule-based policy. Applying domain randomization to the environment in WiseMove yields an even better policy. The final RL policy reduces the failures due to perception errors from 10% to 2.75%. We also observe that the RL policy has significantly less reliance on velocity compared to the rule-based policy, having learned that its measurement is unreliable.
Investigation of Clonal Structure and Self-incompatibility in Japanese Endemic Snow Camellia (Camellia rusticana)

Abstract We investigated the clonal structure, self-incompatibility, and number of seeds per fruit in Camellia rusticana, a Japanese endemic species, in comparison to the closely related C. japonica. Clonal propagation was more vigorous in C. rusticana than in C. japonica and the clonal structure of C. rusticana varied among populations. C. rusticana can maintain genets for extended periods, even in harsh environments such as high-altitude areas with considerable snow accumulation, because even a single surviving genet can propagate clonally. However, sexual reproduction (i.e., reproduction by seed) is advantageous for dispersal to distant suitable habitats. An artificial crossing test revealed high self-incompatibility in C. rusticana, as observed in C. japonica. In addition, the number of seeds per fruit was lower in C. rusticana than in C. japonica. Self-incompatibility in C. rusticana may play a role in production of high-quality seed, despite low seed production.
Exploring the cost-effectiveness of a Dutch collaborative stepped care intervention for the treatment of depression and/or anxiety when adapted to the Australian context: a model-based cost-utility analysis

Abstract Aims Depression and anxiety are among the most common mental health conditions treated in primary care. They frequently co-occur and involve recommended treatments that overlap. Evidence from randomised controlled trials (RCTs) shows specific stepped care interventions to be cost-effective in improving symptom remission. However, most RCTs have focused on either depression or anxiety, which limits their generalisability to routine primary care settings. This study aimed to evaluate the cost-effectiveness of a collaborative stepped care (CSC) intervention to treat depression and/or anxiety among adults in Australian primary care settings. Method A quasi-decision tree model was developed to evaluate the cost-effectiveness of a CSC intervention relative to care-as-usual (CAU). The model adapted a CSC intervention described in a previous Dutch RCT to the Australian context. This 8-month, cluster RCT recruited patients with depression and/or anxiety (n = 158) from 30 primary care clinics in the Netherlands. The CSC intervention involved two steps: (1) guided self-help with a nurse at a primary care clinic; and (2) referral to specialised mental healthcare. The cost-effectiveness model adopted a health sector perspective and synthesised data from two main sources: RCT data on intervention pathways, remission probabilities and healthcare service utilisation; and Australia-specific data on demography, epidemiology and unit costs from external sources. Incremental costs and incremental health outcomes were estimated across a 1-year time horizon. Health outcomes were measured as disability-adjusted life years (DALYs) due to remitted cases of depression and/or anxiety. Incremental cost-effectiveness ratios (ICERs) were measured in 2019 Australian dollars (A$) per DALY averted. Uncertainty and sensitivity analyses were performed to test the robustness of cost-effectiveness findings. Result The CSC intervention had a high probability (99.6%) of being cost-effective relative to CAU. The resulting ICER (A$5207/DALY; 95% uncertainty interval: dominant to 25 345) fell below the willingness-to-pay threshold of A$50 000/DALY. ICERs were robust to changes in model parameters and assumptions. Conclusions This study found that a Dutch CSC intervention, with nurse-delivered guided self-help treatment as a first step, could potentially be cost-effective in treating depression and/or anxiety if transferred to the Australian primary care context. However, adaptations may be required to ensure feasibility and acceptability in the Australian healthcare context. In addition, further evidence is needed to verify the real-world cost-effectiveness of the CSC intervention when implemented in routine practice and to evaluate its effectiveness/cost-effectiveness when compared to other viable stepped care interventions for the treatment of depression and/or anxiety.
Helminth communities in amphibians from Latvia, with an emphasis on their connection to host ecology

Abstract Helminth infracommunities were studied at 174 sites of Latvia in seven hosts from six amphibian taxa of different taxonomical, ontogenic and ecological groups. They were described using a standard set of parasitological parameters, compared by ecological indices and linear discriminant analysis. Their species associations were identified by Kendall's rank correlation, but relationships with host size and waterbody area were analysed by zero-inflated Poisson and zero-inflated negative binomial regressions. The richest communities (25 species) were found in post-metamorphic semi-aquatic Pelophylax spp. frogs, which were dominated by trematode species of both adult and larval stages. Both larval and terrestrial hosts yielded depauperate trematode communities with accession of aquatic and soil-transmitted nematode species, respectively. Nematode loads peaked in terrestrial Bufo bufo. Helminth infracommunities suggested some differences in host microhabitat or food object selection not detected by their ecology studies. Associations were present in 96% of helminth species (on average, 7.3 associations per species) and dominated positive ones. Species richness and abundances, in most cases, were positively correlated with host size, which could be explained by increasing parasite intake rates over host ontogeny (trematode adult stages) or parasite accumulation (larval Alaria alata). Two larval diplostomid species (Strigea strigis, Tylodelphys excavata) had a negative relationship with host size, which could be caused by parasite-induced host mortality. The adult trematode abundances were higher in larger waterbodies, most likely due to their ecosystem richness, while higher larval abundances in smaller waterbodies could be caused by elevated infection rates under high host densities.