Miracle-dz/UniFAR-FTUs huggingface dataset:
Welfare Gains and Social Challenges: The Impact of Refugees on the Host Population in Uganda Not in my backyard? Welfare gains and social challenges: the impact of refugees on the host population in Uganda

This study exploits a natural experiment of three sudden Congolese refugee inflows to causally investigate the impact of an increased exposure to refugee presence on the Ugandan host population. We focus on the effects on female employment, household welfare and social cohesion among the host population. Using a repeated cross-section (preand post-treatment) of Demographic and Health Survey (DHS) data covering the years 2001 to 2011, we find that a higher exposure to our treatment variable increases the probability that Ugandan women are active in the labour market. This effect is mainly driven by agricultural employment. We also find that a higher treatment exposure has a positive impact on household wealth and a beneficial effect on nutritional indicators of children below the age of five. Our qualitative investigation suggests that incoming refugees improved labour market opportunities for Ugandan women, for instance, by increasing demand (such as for agricultural produce) and new marketing channels. These effects translated into positive average welfare effects for the host population. Irrespective of these welfare gains, analysing different dimensions of social cohesion using Afrobarometer data covering the years 2000 to 2012, we found that a higher exposure to our treatment variable was negatively associated with social cohesion indicators: a larger refugee presence was associated, for instance, with a rise in perceived inequality, as well as with lower levels of general trust among the host population. While the underlying mechanisms necessitate future research and a more nuanced analysis, we note that economic gains do not necessarily benefit social cohesion.
Effectiveness and safety over 3 years after the 2-year U-Act-Early trial of the strategies initiating tocilizumab and/or methotrexate

Abstract Objectives U-Act-Early was a 2-year, randomized placebo controlled, double-blind trial, in which DMARD-naïve early RA patients were treated to the target of sustained remission (SR). Two strategies initiating tocilizumab (TCZ), with and without methotrexate (MTX), were more effective than a strategy initiating MTX. The aim of the current study was to determine longer-term effectiveness in daily clinical practice. Methods At the end of U-Act-Early, patients were included in a 3-year post-trial follow-up (PTFU), in which treatment was according to standard care and data were collected every 3 months during the first year and every 6 months thereafter. Primary end point was disease activity score assessing 28 joints (DAS28) over time. Mixed effects models were used to compare effectiveness between initial strategy groups, correcting for relevant confounders. Between the groups as randomized, proportions of patients were tested for DMARD use, SR and radiographic progression of joint damage. Results Of patients starting U-Act-Early, 226/317 (71%) participated in the PTFU. Over the total 5 years, mean DAS28 was similar between groups (P > 0.20). During U-Act-Early, biologic DMARD use decreased in both TCZ initiation groups and increased in the MTX initiation group, but during follow-up this trend did not continue. SR was achieved at least once in 99% of patients. Of the 226 patients, only 30% had any radiographic progression over 5 years, without significant differences between the groups. Conclusion Although in the short-term the strategies initiating TCZ yielded the most clinical benefit, in the longer-term differences in important clinical outcomes between the strategies disappeared, probably due to continuation of the treat-to-target principle.
ALTERED RETINAL PERFUSION IN PATIENTS WITH INACTIVE GRAVES' OPHTHALMOPATHY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Objective: The aim of this study was to evaluate retinal and optic nerve head (ONH) perfusion in patients with inactive Graves' ophthalmopathy (GO) and to compare it to healthy controls using optical coherence tomography angiography (OCTA). Design/Measurements: 29 eyes of 29 patients with inactive GO (study group) and 29 eyes of 29 healthy subjects (control group) were included in this study. The vessel density (VD) data in the superficial and deep retinal OCT angiogram of the macula and the radial peripapillary capillary network (RPC) were extracted and analysed. OCTA was performed using RTVue XR Avanti with AngioVue (Optovue, Inc, Fremont, California, USA). Clinical activity was evaluated by using the clinical activity score (CAS), the severity assessment by using the NOSPECS classification. Results: The VD in the superficial OCT angiogram and in the OCT angiogram of the ONH was significantly lower in the GO group when compared to the control group (whole en face: p=0.016; parafovea: p=0.026; RPC peripapillary: p=0.027). There was no significant correlation between the VD and functional parameters or the NOSPECS classification. Conclusions: Macular VD and ONH capillary density measured using OCTA were significantly lower in the study group compared to healthy controls. Non-invasive quantitative analysis of retinal perfusion using OCTA could be useful in monitoring patients with GO.
Neurofilaments in blood is a new promising preclinical biomarker for the screening of natural scrapie in sheep

Scrapie is a fatal neurodegenerative disease of sheep and goats belonging to the group of Transmissible Spongiform Encephalopathy or prion diseases. The EU has adopted mandatory measures for scrapie surveillance to safeguard public and animal health because it is highly contagious and might decimate all genetic susceptible animals in affected flocks. Definite diagnosis of scrapie relies on the detection of the pathological prion protein in brain tissues and there are still no blood biomarkers available for making diagnosis in living animals that can be used for the screening of sheep in scrapie-affected flocks. Neurofilament light (NfL) protein, a valid biomarker for neuronal and axonal damages, can now be easily measured in blood by the ultra-sensitive single molecule array (Simoa) technology. Recent work reported that serum NfL is increased in neurodegenerative diseases, including human prion diseases, but no data are available for scrapie or other animal prion diseases. Here, we found that the median serum NfL concentration in scrapie animals (56.2, IQR 42.2–84.8, n = 9) was more than 15 times higher (p = 0.00084) than that found in control samples (3.4, IQR 3.0–26.3, n = 11). Moreover, serum NfL concentration in scrapie sheep with clinical signs (n = 2; 75.3, 15.7 pg/ml) did not significantly (p = 0.541; t-test) differ from scrapie animals without clinical signs (n = 7; 61.0, 10.7 pg/ml). The receiver operating characteristic (ROC) curve analysis estimated the cut-off value of 31 pg/ml serum NfL for distinguishing scrapie-infected sheep from controls. The application of this cut-off value gives an accuracy of the test of 95% (percent error of 5.23%). These data indicate that the Simoa test for serum NfL might be a useful screening method for detecting preclinical scrapie in living sheep. Finally, the preliminary data reported here need confirmation in large and more structured studies.
Strategies for the delivery of insoluble drugs to the eye

This thesis explored three new strategies for the delivery of poorly water-soluble drugs to the eye. Cyclosporine A and latanoprost are two drugs currently used in clinics for the treatment of highly prevalent ocular conditions (e.g. dry eye, ocular inflammation or glaucoma). These two drugs were selected as models since they are "practically insoluble" and their topical ophthalmic formulations need to be improved in regards to their stability, safety or availability. The three new strategies were based on: i) the use of a cyclosporine A prodrug, ii) the complexation of latanoprost with cyclodextrins and iii) the intraocular implantation of cyclosporine A loaded drug delivery systems. These three new formulations were demonstrated to be successful in overcoming the challenges with ocular delivery of poorly water-soluble drugs while improving drug stability, safety and availability. These new formulations represent promising options for the successful treatment of ocular conditions with minimal side effects.
Soluble levels of sCD40L and s4‐1BB are associated with a poor prognosis in elderly patients with colorectal cancer

The prognosis of colorectal cancer (CRC) has improved in the last decades, however, a lower overall survival persists in the elderly. The understanding of immunity changes in the elderly with CRC will allow the emergence of new treatments with higher response rates. 4‐1BB and CD40L, an immune checkpoint stimulator, play an important role in T‐cell responses and platelets. Our aim was to characterize the soluble levels of CD40L and 4‐1BB in CRC elderly patients.
Maternal employment and child nutritional status in Uganda

Nearly half of all deaths among children under five (U5) years in low- and middle-income countries are a result of under nutrition. This study examined the relationship between maternal employment and nutrition status of U5 children in Uganda using the 2016 Uganda Demographic and Health Survey (UDHS) data. We used a weighted sample of 3531 children U5 years born to working women age 15–49. Chi-squared tests and multivariate logistic regressions were used to examine the relationship between maternal employment and nutritional outcomes while adjusting for other explanatory factors. Results show that children whose mothers had secondary education had lower odds of stunting and underweight compared with children whose mothers had no formal education. Children who had normal birth weight had lower odds of stunting, wasting and being underweight compared with children with low birth weight. Children whose mothers engaged in agriculture and manual work had higher odds of stunting compared with those whose mothers engaged in professional work. Additionally, children whose mothers were employed by nonfamily members had higher odds of wasting and being underweight compared with children whose mothers were employed by family members. Other determinants of child nutritional status included region, age of the mother, and age and sex of the child. Interventions aimed at improving the nutritional status of children of employed women should promote breastfeeding and flexible conditions in workplaces, target those of low socio-economic status and promote feeding programs and mosquito net use for both mothers and children.
Use of rapid diagnostic tests (RDTs) for conclusive diagnosis of chronic Chagas disease – field implementation in the Bolivian Chaco region

Chagas disease, caused by the parasite Trypanosoma cruzi, is the neglected tropical disease with a highest burden in Latin America. Its acute stage is mostly asymptomatic and goes unnoticed. Symptoms appear at the chronic stage, which is when diagnosis is usually made. This is based on the agreement of two conventional serological tests such as Enzyme-Linked Immunosorbent Assays (ELISAs). There are commercial kits with good sensitivity and specificity but their use is impractical in many highly endemic regions with poorly equipped laboratories. Luckily, several rapid diagnostic tests (RDTs) are available for the detection of anti-T. cruzi immunoglobulins. They are easy to operate, require no cold storage, provide fast turnaround of results, and some can work with a tiny volume of whole blood as sample. With the aim to field validate their use we compared an alternative algorithm based on a combination of RDTs with the standard based on ELISAs. In both cases a third test was available in case of discordance. RDTs were implemented by mobile teams in field campaigns to detect chronic T. cruzi-infections in the Chaco region of Bolivia. ELISAs were made in the reference laboratories located in the main hospitals of Yacuiba and Villa Montes, two major cities of the region. We enrolled 685 subjects who voluntarily participated in the study and had not been treated against the disease before. The agreement between the two main RDTs was 93.1% (638/685) (kappa index = 0.86; CI 95% 0.83–0.90). In comparison to the ELISAs algorithm, the combined use of the RDTs provided a sensitivity of 97.7% and a specificity of 96.1%. These results support the use of RDTs for the diagnosis of chronic Chagas disease in the studied region, and encourage their evaluation in other regions of Bolivia and other endemic countries.
Environmental Toxicology and Chemistry

Tritium, a radioactive isotope of hydrogen of natural and anthropogenic origin, is ubiquitously present in the environment. Effluents of nuclear centers of production are significant anthropogenic sources. With the upcoming project of thermonuclear fusion, tritium releases in the environment may increase. It is therefore important to characterize the ecological risk linked to tritium. The effects of tritiated water (HTO) were therefore studied in zebrafish larvae exposed for 10 d to different dose rates, 1.1 × 10, 4.1 × 10, and 3.8 × 10 μGy/h for larvae corresponding, respectively, to a water contamination of 10, 10, and 10 Bq/mL of HTO. Those dose rates were higher than 10 μGy/h, which is the threshold recommended to start monitoring ecosystems where radiological contaminants are present. Mortality, embryo‐larval development, immune toxicity, genotoxicity, neurotoxicity, and alterations of tissues were investigated. The results showed that HTO exposure induced DNA damage and reactive oxygen species production and modulated the expression of genes involved in detoxification processes. Moreover, modifications of the muscular tissues (degradation of myofibrils at 4 d post fertilization and disorganization of mitochondria at later stages) were observed. The results differed with HTO dose rates and with developmental stages. These results will drive future research for the development of new HTO‐sensitive biomarkers and will allow us to progress in the characterization of the modes of action of tritium in fish. Environ Toxicol Chem 2020;39:648–658. © 2019 SETAC
The polarity protein Dlg5 regulates collective cell migration during Drosophila oogenesis

Collective migration plays critical roles in animal development, physiological events, and cancer metastasis. However, the molecular mechanisms of collective cell migration are not well understood. Drosophila border cells represent an excellent in vivo genetic model to study collective cell migration and identify novel regulatory genes for cell migration. Using the Mosaic Analysis with a Repressible Cell Marker (MARCM) system, we screened 240 P-element insertion lines to identify essential genes for border cell migration. Two genes were uncovered, including dlg5 (discs large 5) and CG31689. Further analysis showed that Dlg5 regulates the apical-basal polarity and cluster integrity in border cell clusters. Dlg5 is enriched in lateral surfaces between border cells and central polar cells but also shows punctate localization between border cells. We found that the distribution of Dlg5 in border cell clusters is regulated by Armadillo. Structure-function analysis revealed that the N-terminal Coiled-coil domain and the C-terminal PDZ3-PDZ4-SH3-GUK domains but not the PDZ1-PDZ2 domains of Dlg5 are required for BC migration. The Coiled-coil domain and the PDZ4-SH3-GUK domains are critical for Dlg5’s cell surface localization in border cell clusters.
Implementation of Bayesian Multiple Comparison Correction in the Second-Level Analysis of fMRI Data: With Pilot Analyses of Simulation and Real fMRI Datasets Based on Voxelwise Inference

We developed and tested Bayesian multiple comparison correction method for Bayesian voxelwise second-level fMRI analysis with R. The performance of the developed method was tested with simulation and real image datasets. First, we compared false alarm and hit rates, which were used as proxies for selectivity and sensitivity, respectively, between Bayesian and classical inference were conducted. For the comparison, we created simulated images, added noise to the created images, and analyzed the noise-added images while applying Bayesian and classical multiple comparison correction methods. Second, we analyzed five real image datasets to examine how our Bayesian method worked in realistic settings. When the performance assessment was conducted, Bayesian correction method demonstrated good sensitivity (hit rate ≥ 75%) and acceptable selectivity (false alarm rate < 10%) when N ≤ 8. Furthermore, Bayesian correction method showed better sensitivity compared with classical correction method while maintaining the aforementioned acceptable selectivity.
An interesting increase in immediate and residual efficacy of a trade mark of alcoholic 2% chlorhexidine gluconate, with and without dye, has been demonstrated by an in vitro study with ATCC micro‐organisms and strains isolated from ICU patients

ChloraPrep™ (CHP) is a clear solution of 2% (w/v) chlorhexidine (CHG) in 70% (v/v) isopropyl alcohol (IPA) administered with a specially designed sterile single‐use applicator in which a tinting agent can be added to the CHP solution upon activation of applicator immediately prior to patient skin preparation (CHP+T). This study investigated whether the immediate and residual efficacy of CHP vs CHP+T and a stock solution of 2% CHG in 70% IPA varied, and whether CHP was compromised by the addition of the dye.
Detecting G protein-coupled receptor complexes in postmortem human brain with proximity ligation assay and a Bayesian classifier

Despite the controversy regarding the existence and physiological relevance of class A G protein-coupled receptor dimerization, there is substantial evidence for functional interactions between the dopamine D2 receptor (D2R) and the adenosine A2A receptor (A2AR). A2AR-D2R complexes have been detected in rodent brains by proximity ligation assay; however, their existence in the human brain has not been demonstrated. In this study, we used Brightfield proximity ligation assay, combined with a systematic sampling and a parameter-free naive Bayesian classifier, and demonstrated proximity between the D2R and the A2AR in the adult human ventral striatum, consistent with their colocalization within complexes and the possible existence of D2R-A2AR heteromers. These methods are applicable to the relative quantification of proximity of two proteins, as well as the expression levels of individual proteins.
Polysubstance Use: A Broader Understanding of Substance Use During the Opioid Crisis.

Objectives. To understand important changes in co-occurring opioid and nonopioid drug use (i.e., polysubstance use) within the opioid epidemic in the United States.Methods. We analyzed survey data on the past month co-use of prescription and illicit opioids and 12 nonopioid psychoactive drug classes from a national sample of 15 741 persons entering treatment of opioid use disorder.Results. Past-month illicit opioid use increased from 44.8% in 2011 to 70.1% in 2018, while the use of prescription opioids alone dropped from 55.2% to 29.9%, yet overall remained high (94.5% to 85.2%). Past-month use of at least 1 nonopioid drug occurred in nearly all participants (> 90%), with significant increases in methamphetamine (+85%) and decreases across nonopioid prescription drug classes (range: -40% to -68%). Conclusions. Viewing opioid trends in a "silo" ignores the fact not only that polysubstance use is ubiquitous among those with opioid use disorder but also that significant changes in polysubstance use should be monitored alongside opioid trends.Public Health Implications. Treatment, prevention, and policymaking must address not only the supply and demand of a singular drug class but also the global nature of substance use overall. (Am J Public Health. Published online ahead of print December 19, 2019: e1-e7. doi:10.2105/AJPH.2019.305412).
Developing and using a structured, conversation-based intervention for clarifying values and preferences for end-of-life in the advance care planning-naïve Swedish context: Action research within the DöBra research program

Abstract Sweden has no systematic advance care planning (ACP), nor legal recognition of end-of-life proxies. We describe our experiences and reflections from a participatory action research process, aiming at developing and initially using a conversation-based, structured ACP approach among community-dwelling, older adults in Sweden. Eco-mapping and DöBra cards were used with 65 people to catalyze discussions on preferences for the end-of-life. We found great individual variation in both Eco-map depictions of social networks and prioritization of the 37 DöBra card items. The DöBra cards were concluded to be a viable tool for stimulating person-centered conversations on preferences for future end-of-life care.
A diverse uncultivated microbial community is responsible for organic matter degradation in the Black Sea sulphidic zone

Summary Organic matter degradation in marine environments is essential for the recycling of nutrients, especially under conditions of anoxia where organic matter tends to accumulate. However, little is known about the diversity of the microbial communities responsible for the mineralization of organic matter in the absence of oxygen, as well as the factors controlling their activities. Here, we determined the active heterotrophic prokaryotic community in the sulphidic water column of the Black Sea, an ideal model system, where a tight coupling between carbon, nitrogen and sulphur cycles is expected. Active microorganisms degrading both dissolved organic matter (DOM) and protein extracts were determined using quantitative DNA stable isotope probing incubation experiments. These results were compared with the metabolic potential of metagenome‐assembled genomes obtained from the water column. Organic matter incubations showed that groups like Cloacimonetes and Marinimicrobia are generalists degrading DOM. Based on metagenomic profiles the degradation proceeds in a potential interaction with members of the Deltaproteobacteria and Chloroflexi Dehalococcoidia. On the other hand, microbes with small genomes like the bacterial phyla Parcubacteria, Omnitrophica and of the archaeal phylum Woesearchaeota, were the most active, especially in protein‐amended incubations, revealing the potential advantage of streamlined microorganisms in highly reduced conditions.
Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway 1

Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.