Miracle-dz/UniFAR-FTUs huggingface dataset:
The Female Athlete Body project study: 18-month outcomes in eating disorder symptoms and risk factors.

OBJECTIVE To evaluate the efficacy of the Female Athlete Body project (FAB) in reducing eating disorder (ED) symptoms and risk factors. METHOD This study was a community participatory three-site, two-arm, cluster randomized controlled trial (RCT). Female collegiate athletes (N = 481) were randomly assigned by team to the FAB intervention, a behavioral ED risk factor reduction program, or a waitlist control condition. Primary analyses examined 18-month effects for ED pathology. Secondary analyses examined risk factors and correlates (e.g., thin-ideal internalization, negative mood, Female Athlete Triad knowledge, and body mass index [BMI]). RESULTS Linear mixed effects models with team as a cluster level variable and study condition as a between-subjects variable revealed significantly reduced dietary restraint in FAB teams relative to control teams. FAB teams also reported significantly fewer objective and subjective binge episodes than control teams. Finally, FAB teams showed significantly lower thin-ideal internalization and increased BMI at 18-months. No other significant differences were found. DISCUSSION This RCT examined the effects of a short intervention on ED pathology and risk factors in female collegiate athletes through 18-month follow-up. This trial is one of only three trials with female athletes that have shown long-term reductions in any ED symptoms or produced positive effects on ED risk factors. The present study is the first to find such effects with athletes using a brief (i.e., 4 hr) intervention at 18-month follow-up. Although small effects were found, the current trial provides valuable lessons about future design and implementation of similar trials with athletes. TRIAL REGISTRATION Clinical trials NCT01735994.
Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) in Eyes With Pigment Epithelial Detachments Due to Age-Related Macular Degeneration

Purpose To investigate fluorescence lifetime imaging ophthalmoscopy (FLIO) in neovascular AMD and pigment epithelial detachments (PEDs). Methods A total of 46 eyes with PEDs (>350 μm) as well as age-matched healthy controls were included in this study. We found 28 eyes showed neovascular AMD (nvAMD), and 17 had nonneovascular (dry) AMD (dAMD). The Heidelberg Engineering FLIO excited fluorescence at 473 nm. Fluorescence decays were detected in two spectral channels (498–560 nm; 560–720 nm) to determine fluorescence lifetimes of endogenous fluorophores in their specific spectral emission ranges. Mean fluorescence lifetimes (τm) were investigated. Multimodal imaging was reviewed by two ophthalmologists who circumscribed and classified PEDs as either serous (n = 4), hemorrhagic (n = 4), fibrovascular (n = 16), drusenoid (n = 17), or mixed (n = 5). Blood samples from a healthy subject and a patient with PED were investigated in a quartz cuvette. Results Eyes with nvAMD show similar FLIO patterns to dAMD: ring-shaped prolongations of τm 3 to 6 mm from the fovea. Different PED-forms show characteristic τm, while serous and hemorrhagic PEDs exhibit shortened τm, drusenoid PEDs show prolonged τm, and τm in fibrovascular PEDs is variable. Areas corresponding to sub-/intraretinal fluid display shortened τm. Ex vivo studies of blood also show short τm. Conclusions The previously described dAMD-related FLIO pattern is also present in nvAMD. Short τm in serous, fibrovascular, and hemorrhagic PEDs as well as sub/intraretinal fluid may disrupt this pattern. FLIO appears to differentiate between PEDs, hemorrhage, and fluid. Additionally, ex vivo studies of human blood help to better interpret FLIO images.
Economics of Security Working Paper Series

This study aims to identify robust push and pull factors of human trafficking. I test for the robustness of 78 push and 67 pull factors suggested in the literature. By employing an extreme bound analysis, running more than two million regressions with all possible combinations of variables for up to 180 countries during the period of 1995-2010, I show that crime prevalence robustly explains human trafficking prevalence both in destination and origin countries. My finding also implies that a low level of gender equality and development may have constraining effects on human trafficking outflows, contrary to expectations. The linkage between migration and human trafficking is less clear, and institutional quality matters more in origin countries than destinations.
Airborne concentrations and chemical considerations of radioactive ruthenium from an undeclared major nuclear release in 2017

Significance A massive atmospheric release of radioactive 106Ru occurred in Eurasia in 2017, which must have been caused by a sizeable, yet undeclared nuclear accident. This work presents the most compelling monitoring dataset of this release, comprising 1,100 atmospheric and 200 deposition data points from the Eurasian region. The data suggest a release from a nuclear reprocessing facility located in the Southern Urals, possibly from the Mayak nuclear complex. A release from a crashed satellite as well as a release on Romanian territory (despite high activity concentrations) can be excluded. The model age of the radioruthenium supports the hypothesis that fuel was reprocessed ≤2 years after discharge, possibly for the production of a high-specific activity 144Ce source for a neutrino experiment in Italy. In October 2017, most European countries reported unique atmospheric detections of aerosol-bound radioruthenium (106Ru). The range of concentrations varied from some tenths of µBq·m−3 to more than 150 mBq·m−3. The widespread detection at such considerable (yet innocuous) levels suggested a considerable release. To compare activity reports of airborne 106Ru with different sampling periods, concentrations were reconstructed based on the most probable plume presence duration at each location. Based on airborne concentration spreading and chemical considerations, it is possible to assume that the release occurred in the Southern Urals region (Russian Federation). The 106Ru age was estimated to be about 2 years. It exhibited highly soluble and less soluble fractions in aqueous media, high radiopurity (lack of concomitant radionuclides), and volatility between 700 and 1,000 °C, thus suggesting a release at an advanced stage in the reprocessing of nuclear fuel. The amount and isotopic characteristics of the radioruthenium release may indicate a context with the production of a large 144Ce source for a neutrino experiment.
Mapping the Solastalgia Literature: A Scoping Review Study

Solastalgia is a relatively new concept for understanding the links between human and ecosystem health, specifically, the cumulative impacts of climatic and environmental change on mental, emotional, and spiritual health. Given the speed and scale of climate change alongside biodiversity loss, pollution, deforestation, unbridled resource extraction, and other environmental challenges, more and more people will experience solastalgia. This study reviewed 15 years of scholarly literature on solastalgia using a scoping review process. Our goal was to advance conceptual clarity, synthesize the literature, and identify priorities for future research. Four specific questions guided the review process: (1) How is solastalgia conceptualized and applied in the literature? ; (2) How is solastalgia experienced and measured in the literature? ; (3) How is ‘place’ understood in the solastalgia literature? ; and (4) Does the current body of literature on solastalgia engage with Indigenous worldviews and experiences? Overall, we find there is a need for additional research employing diverse methodologies, across a greater diversity of people and places, and conducted in collaboration with affected populations and potential knowledge, alongside greater attention to the practical implications and applications of solastalgia research. We also call for continued efforts to advance conceptual clarity and theoretical foundations. Key outcomes of this study include our use of the landscape construct in relation to solastalgia and a call to better understand Indigenous peoples’ lived experiences of landscape transformation and degradation in the context of historical traumas.
A general protein O-glycosylation machinery conserved in Burkholderia species improves bacterial fitness and elicits glycan immunogenicity in humans

The Burkholderia genus encompasses many Gram-negative bacteria living in the rhizosphere. Some Burkholderia species can cause life-threatening human infections, highlighting the need for clinical interventions targeting specific lipopolysaccharide proteins. Burkholderia cenocepacia O-linked protein glycosylation has been reported, but the chemical structure of the O-glycan and the machinery required for its biosynthesis are unknown and could reveal potential therapeutic targets. Here, using bioinformatics approaches, gene-knockout mutants, purified recombinant proteins, LC-MS–based analyses of O-glycans, and NMR-based structural analyses, we identified a B. cenocepacia O-glycosylation (ogc) gene cluster necessary for synthesis, assembly, and membrane translocation of a lipid-linked O-glycan, as well as its structure, which consists of a β-Gal-(1,3)–α-GalNAc-(1,3)–β-GalNAc trisaccharide. We demonstrate that the ogc cluster is conserved in the Burkholderia genus, and we confirm the production of glycoproteins with similar glycans in the Burkholderia species: B. thailandensis, B. gladioli, and B. pseudomallei. Furthermore, we show that absence of protein O-glycosylation severely affects bacterial fitness and accelerates bacterial clearance in a Galleria mellonella larva infection model. Finally, our experiments revealed that patients infected with B. cenocepacia, Burkholderia multivorans, B. pseudomallei, or Burkholderia mallei develop O-glycan–specific antibodies. Together, these results highlight the importance of general protein O-glycosylation in the biology of the Burkholderia genus and its potential as a target for inhibition or immunotherapy approaches to control Burkholderia infections.
Ergochromes: Heretofore Neglected Side of Ergot Toxicity

Ergot, fungal genus Claviceps, are worldwide distributed grass pathogens known for their production of toxic ergot alkaloids (EAs) and the great agricultural impact they have on both cereal crop and farm animal production. EAs are traditionally considered as the only factor responsible for ergot toxicity. Using broad sampling covering 13 ergot species infecting wild or agricultural grasses (including cereals) across Europe, USA, New Zealand, and South Africa we showed that the content of ergochrome pigments were comparable to the content of EAs in sclerotia. While secalonic acids A–C (SAs), the main ergot ergochromes (ECs), are well known toxins, our study is the first to address the question about their contribution to overall ergot toxicity. Based on our and published data, the importance of SAs in acute intoxication seems to be negligible, but the effect of chronic exposure needs to be evaluated. Nevertheless, they have biological activities at doses corresponding to quantities found in natural conditions. Our study highlights the need for a re-evaluation of ergot toxicity mechanisms and further studies of SAs’ impact on livestock production and food safety.
Heterogeneity and plasticity in healthy and atherosclerotic vasculature explored by single-cell sequencing

Abstract Cellular characteristics and their adjustment to a state of disease have become more evident due to recent advances in imaging, fluorescent reporter mice, and whole genome RNA sequencing. The uncovered cellular heterogeneity and/or plasticity potentially complicates experimental studies and clinical applications, as markers derived from whole tissue ‘bulk’ sequencing is unable to yield a subtype transcriptome and specific markers. Here, we propose definitions on heterogeneity and plasticity, discuss current knowledge thereof in the vasculature and how this may be improved by single-cell sequencing (SCS). SCS is emerging as an emerging technique, enabling researchers to investigate different cell populations in more depth than ever before. Cell selection methods, e.g. flow assisted cell sorting, and the quantity of cells can influence the choice of SCS method. Smart-Seq2 offers sequencing of the complete mRNA molecule on a low quantity of cells, while Drop-seq is possible on large numbers of cells on a more superficial level. SCS has given more insight in heterogeneity in healthy vasculature, where it revealed that zonation is crucial in gene expression profiles among the anatomical axis. In diseased vasculature, this heterogeneity seems even more prominent with discovery of new immune subsets in atherosclerosis as proof. Vascular smooth muscle cells and mesenchymal cells also share these plastic characteristics with the ability to up-regulate markers linked to stem cells, such as Sca-1 or CD34. Current SCS studies show some limitations to the number of replicates, quantity of cells used, or the loss of spatial information. Bioinformatical tools could give some more insight in current datasets, making use of pseudo-time analysis or RNA velocity to investigate cell differentiation or polarization. In this review, we discuss the use of SCS in unravelling heterogeneity in the vasculature, its current limitations and promising future applications.
Efficacy of a plant‐produced virus‐like particle vaccine in chickens challenged with Influenza A H6N2 virus

Summary The efficacy, safety, speed, scalability and cost‐effectiveness of producing hemagglutinin‐based virus‐like particle (VLP) vaccines in plants are well‐established for human influenza, but untested for the massive poultry influenza vaccine market that remains dominated by traditional egg‐grown oil‐emulsion whole inactivated virus vaccines. For optimal efficacy, a vaccine should be closely antigenically matched to the field strain, requiring that influenza A vaccines be updated regularly. In this study, an H6 subtype VLP transiently expressed in Nicotiana benthamiana was formulated into a vaccine and evaluated for efficacy in chickens against challenge with a heterologous H6N2 virus. A single dose of the plant‐produced H6 VLP vaccine elicited an immune response comparable to two doses of a commercial inactivated H6N2 vaccine, with mean hemagglutination inhibition titres of 9.3 log2 and 8.8 log2, respectively. Compared to the non‐vaccinated control, the H6 VLP vaccine significantly reduced the proportion of shedders and the magnitude of viral shedding by >100‐fold in the oropharynx and >6‐fold in the cloaca, and shortened oropharyngeal viral shedding by at least a week. Despite its potency, the cost of the antigenic mismatch between the inactivated H6N2 vaccine and challenge strain was evident not only in this vaccine's failure to reduce viral shedding compared to the non‐vaccinated group, but its apparent exacerbation of oropharyngeal viral shedding until 21 days post‐challenge. We estimate that a kilogram of plant leaf material can produce H6 VLP vaccines sufficient for between 5000 and 30 000 chickens, depending on the effective dose and whether one or two immunizations are administered.
The Role of Muscle Mass Gain Following Protein Supplementation Plus Exercise Therapy in Older Adults with Sarcopenia and Frailty Risks: A Systematic Review and Meta-Regression Analysis of Randomized Trials

Aging and frailty are associated with a high risk of lean mass (LM) loss, which leads to physical disability and can be effectively alleviated by protein supplementation (PS) and muscle strengthening exercise (MSE). In this study, the associations between LM gain and PS + MSE efficacy (measured using physical outcomes) in elderly patients with a high risk of sarcopenia or frailty were identified. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) reporting the efficacy of PS + MSE in elderly patients with sarcopenia or frailty. The included RCTs were analyzed using meta-analysis and risk of bias assessment. We finally included 19 RCTs in this meta-analysis with a median (range/total) Physiotherapy Evidence Database score of 7/10 (5–9/10). The PS + MSE group exhibited significant improvements in the whole-body LM (standard mean difference (SMD) = 0.66; p < 0.00001), appendicular LM (SMD = 0.35; p < 0.00001), leg strength (SMD = 0.65; p < 0.00001), and walking capability (SMD = 0.33; p = 0.0006). Meta-regression analyses showed that changes in appendicular LM were significantly associated with the effect sizes of leg strength (β = 0.08; p = 0.003) and walking capability (β = 0.17; p = 0.04), respectively. Our findings suggest that LM gain after PS + MSE significantly contributes to the efficacy of the intervention in terms of muscle strength and physical mobility in elderly patients with a high risk of sarcopenia or frailty.
A graph representation of functional diversity of brain regions

Modern network science techniques are popularly used to characterize the functional organization of the brain. A major challenge in network neuroscience is to understand how functional characteristics and topological architecture are related in the brain. Previous task‐based functional neuroimaging studies have uncovered a core set of brain regions (e.g., frontal and parietal) supporting diverse cognitive tasks. However, the graph representation of functional diversity of brain regions remains to be understood.
Astragalus polysaccharide (PG2) Ameliorates Cancer Symptom Clusters, as well as Improves Quality of Life in Patients with Metastatic Disease, through Modulation of the Inflammatory Cascade

Background: Improving patients’ quality of life (QoL) is a principal objective of all treatment in any clinical setting, including oncology practices. Cancer-associated inflammation is implicated in disease progression and worsening of patients’ QoL. Conventional anticancer therapeutics while selectively eliminating cancerous cells, are evaded by stem cell-like cells, and associated with varying degrees of adverse effects, thus reducing patients’ QoL. This necessitates novel therapeutic approaches with enhanced efficacy, minimal or no treatment-related adverse effects, and improved QoL in patients with cancer, especially those with metastatic/advance stage disease. Methods: Sequel to our team’s previous publication, the present study explores probable effects of Astragalus polysaccharides (PG2) on cancer-related inflammatory landscape and known determinants of QoL, as well as the probable link between the two to provide mechanistic insight. In an exploratory double blind randomized controlled trial using patients with metastatic disease (n = 23), we comparatively evaluated the therapeutic efficacy of high (500 mg) or low (250 mg) dose PG2 administered intravenously (i.v.), with particular focus on its suggested anti-inflammatory function and the probable effect of same on QoL indices at baseline, then at weeks 4 and 8 post-PG2 treatment. Results: All 23 patients with metastatic disease treated with either low or high PG2 experienced reduced pain, nausea, vomiting, and fatigue, as well as better appetite and sleep, culminating in improved global QoL. This was most apparent in the high dose group, with significant co-suppression of pro-inflammatory interleukin (IL)-1β, IL-4, IL-6, IL-13, IL-17, monocytes chemotactic protein (MCP)1, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), tumor growth factor (TGF)-β1, interferon (IFN)-γ, and immune suppressors IL-10 and IL-12. Univariate and multivariate analyses revealed that IL-1β, IL-13 and GM-CSF are independent prognosticators of improved QoL. Conclusion: This proof-of-concept study provides premier evidence of functional association between PG2 anti-inflammatory effects and improved QoL in patients with advanced stage cancers, laying the groundwork for future larger cohort blinded controlled trials to establish the efficacy of PG2 as adjuvant anticancer therapy in metastatic or advanced stage clinical settings.
Clinical benefit of two-times-per-day aclidinium bromide compared with once-a-day tiotropium bromide hydrate in COPD: a multicentre, open-label, randomised study

Objective Chronic obstructive pulmonary disease (COPD) is mainly treated pharmaceutically with bronchodilators. The purpose of this study was to evaluate the clinical benefits of two-times-per-day aclidinium bromide (Acli-BID) compared with once-a-day tiotropium bromide hydrate (Tio-QD) in patients with COPD. Design This study was a multicentre, open-label, randomised study. Setting Fourcentres in Kagawa prefecture, Japan. Participant Patients who were diagnosed to have COPD Grade 2–3 according to the Global Initiative for Chronic Obstructive Lung Disease 2015 criteria were enrolled. Interventions Patients were randomly assigned to receive Acli-BID or Tio-QD at a 1:1 ratio, and followed for 8 weeks. Acli-BID was administered in the morning and night, and Tio-QD was administered in the night. Primary and secondary outcome measures Primary outcome was forced expiratory volume in one second area under the curve (FEV1AUC0-3), and secondary outcomes were pulmonary function, physical activity, St George’s Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC), the 8-item Short-Form Health Survey (SF-8) and COPD exacerbations. Adverse events were evaluated during the study. Results 44 patients were included in this study. FEV1AUC0-3 at week 8 was 4.62±1.43 L·hour in Acli-BID and 4.73±1.60 L·hour in Tio-QD (mean difference (MD) −0.11 L·hour; 95% CI), −1.04 to 0.83). Significant improvement was observed in activity-related subscales of SGRQ (MD −7.78; 95% CI −14.61 to −0.94) and SF-8 (MD 4.01; 95% CI 0.37 to 7.65), mMRC (MD −0.66; 95% CI −1.19 to −0.13) and rate ratio (0.52, 95% CI 0.27 to 0.99) of exacerbations in the Acli-BID compared with the Tio-QD. Acli-BID and Tio-QD significantly improved sedentary behaviour (MD −35.20 min; 95% CI −67.41 to −2.94 and MD −55.40 min; 95% CI −98.15 to −12.77) within each group, but there was no significant difference between the two groups. Conclusion Acli-BID as with Tio-QD could be one of the therapeutic options for patients with COPD to improve pulmonary function. Also, our results suggest that intervention with bronchodilators enhanced physical activity in patients with COPD. Trial registration number UMIN 000020020.
A difference degree test for comparing brain networks

Recently, there has been a proliferation of methods investigating functional connectivity as a biomarker for mental disorders. Typical approaches include massive univariate testing at each edge or comparisons of network metrics to identify differing topological features. Limitations of these methods include low statistical power due to the large number of comparisons and difficulty attributing overall differences in networks to local variation. We propose a method to capture the difference degree, which is the number of edges incident to each region in the difference network. Our difference degree test (DDT) is a two‐step procedure for identifying brain regions incident to a significant number of differentially weighted edges (DWEs). First, we select a data‐adaptive threshold which identifies the DWEs followed by a statistical test for the number of DWEs incident to each brain region. We achieve this by generating an appropriate set of null networks which are matched on the first and second moments of the observed difference network using the Hirschberger–Qi–Steuer algorithm. This formulation permits separation of the network's true topology from the nuisance topology induced by the correlation measure that alters interregional connectivity in ways unrelated to brain function. In simulations, the proposed approach outperforms competing methods in detecting differentially connected regions of interest. Application of DDT to a major depressive disorder dataset leads to the identification of brain regions in the default mode network commonly implicated in this ruminative disorder.