julilili42/papers huggingface dataset:
Therapeutic Iloprost for the treatment of acute respiratory distress syndrome (ARDS) (the ThIlo-Trial): a prospective, randomized, multicenter phase II study
2020-01-23

Abstract Background Acute respiratory distress syndrome (ARDS) is caused by rapid onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of ARDS patients, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS. Methods The Therapeutic Iloprost during ARDS ( ThIIo-Trial) is a multicenter, randomized, clinical phase II trial assessing the efficacy of inhaled Iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index, a health care-related questionnaire and frailty (Vulnerable Elderly Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO 2 /FiO 2 . Secondary endpoints include 90-day all-cause mortality, SOFA scores during the study period up to day 90, the duration of mechanical ventilation, the length of ICU stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness and discharge localization. The study will be conducted in three university ARDS centers in Germany. Discussion The results of the ThIlo-Trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in ARDS patients.
Antigens in water-in-oil emulsion: a simple antigen extraction method for analysis and proof of equal antigen distribution in vaccination syringe after mixture
2020-01-23

Abstract Therapeutic vaccination of antigens in oil emulsions is an approach becoming increasingly popular. Water-in-oil emulsions enable the formation of a depot, a slow passive antigen release and a decelerated antigen degradation. Furthermore, particularly advantageous for peptide vaccinations with a low clinical response rate is the increased immunogenicity and activation of CD8 + and CD4 + T-cells. Therefore, the use of personalized peptide vaccination cocktails in oil emulsions are tested in the treatment of cancer patients. An equal peptide distribution in the emulsion is striking for a successful depot effect to ensure the optimal efficacy and additionally, to enable reliable drug release analytics. First, the stability of the generated peptide-Montanide ISATM51 emulsion was demonstrated with a cocktail of heterogeneous peptides for 24 h in room temperature. Furthermore, we developed a simple peptide extraction method to investigate the equal peptide distribution in a Montanide ISATM51 emulsion in the syringe after mixing. Peptides were successfully extracted from a peptide-Montanide ISATM51 vaccination cocktail in sufficient volume for analysis and an equal peptide distribution in the syringe was verified via HPLC.
Professional mathematicians do not differ from others in the symbolic numerical distance and size effects
2020-01-23

The numerical distance effect (it is easier to compare numbers that are further apart) and size effect (for a constant distance, it is easier to compare smaller numbers) characterize symbolic number processing. However, evidence for a relationship between these two basic phenomena and more complex mathematical skills is mixed. Previously this relationship has only been studied in participants with normal or poor mathematical skills, not in mathematicians. Furthermore, the prevalence of these effects at the individual level is not known. Here we compared professional mathematicians, engineers, social scientists, and a reference group using the symbolic magnitude classification task with single-digit Arabic numbers. The groups did not differ with respect to symbolic numerical distance and size effects in either frequentist or Bayesian analyses. Moreover, we looked at their prevalence at the individual level using the bootstrapping method: while a reliable numerical distance effect was present in almost all participants, the prevalence of a reliable numerical size effect was much lower. Again, prevalence did not differ between groups. In summary, the phenomena were neither more pronounced nor more prevalent in mathematicians, suggesting that extremely high mathematical skills neither rely on nor have special consequences for analogue processing of symbolic numerical magnitudes.
ARF1 dimerization is essential for vesicle trafficking and dependent on activation by ARF-GEF dimers in Arabidopsis
2020-01-23

Abstract Membrane traffic maintains the organization of the eukaryotic cell and delivers cargo proteins to their subcellular destinations such as sites of action or degradation. Membrane vesicle formation requires ARF GTPase activation by the SEC7 domain of ARF guanine-nucleotide exchange factors (ARF-GEFs), resulting in the recruitment of coat proteins by GTP-bound ARFs. In vitro exchange assays were done with monomeric proteins, although ARF-GEFs have been shown to form dimers in vivo . This feature is conserved across the eukaryotes, however its biological significance is unknown. Here we demonstrate ARF1 dimerization in vivo and we show that ARF-GEF dimers mediate ARF1 dimer formation. Mutational disruption of ARF1 dimers interfered with ARF1-dependent trafficking but not coat protein recruitment in Arabidopsis. Mutations disrupting simultaneous binding of two ARF1•GDPs by the two SEC7 domains of GNOM ARF-GEF dimer prevented stable interaction of ARF1 with ARF-GEF and thus, efficient ARF1 activation. Our results suggest a model of activation-dependent dimerization of membrane-inserted ARF1•GTP molecules required for coated membrane vesicle formation. Considering the evolutionary conservation of ARFs and ARF-GEFs, this initial regulatory step of membrane trafficking might well occur in eukaryotes in general.
Tracking complex mixtures of chemicals in our changing environment
2020-01-24

Chemicals have improved our quality of life, but the resulting environmental pollution has the potential to cause detrimental effects on humans and the environment. People and biota are chronically exposed to thousands of chemicals from various environmental sources through multiple pathways. Environmental chemists and toxicologists have moved beyond detecting and quantifying single chemicals to characterizing complex mixtures of chemicals in indoor and outdoor environments and biological matrices. We highlight analytical and bioanalytical approaches to isolating, characterizing, and tracking groups of chemicals of concern in complex matrices. Techniques that combine chemical analysis and bioassays have the potential to facilitate the identification of mixtures of chemicals that pose a combined risk.
Bacterial Immunogenicity Is Critical for the Induction of Regulatory B Cells in Suppressing Inflammatory Immune Responses
2020-01-24

B cells fulfill multifaceted functions that influence immune responses during health and disease. In autoimmune diseases, such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, depletion of functional B cells results in an aggravation of disease in humans and respective mouse models. This could be due to a lack of a pivotal B cell subpopulation: regulatory B cells (Bregs). Although Bregs represent only a small proportion of all immune cells, they exhibit critical properties in regulating immune responses, thus contributing to the maintenance of immune homeostasis in healthy individuals. In this study, we report that the induction of Bregs is differentially triggered by the immunogenicity of the host microbiota. In comparative experiments with low immunogenic <i>Bacteroides vulgatus</i> and strong immunogenic <i>Escherichia coli</i>, we found that the induction and longevity of Bregs depend on strong Toll-like receptor activation mediated by antigens of strong immunogenic commensals. The potent B cell stimulation via <i>E. coli</i> led to a pronounced expression of suppressive molecules on the B cell surface and an increased production of anti-inflammatory cytokines like interleukin-10. These bacteria-primed Bregs were capable of efficiently inhibiting the maturation and function of dendritic cells (DCs), preventing the proliferation and polarization of T helper (Th)1 and Th17 cells while simultaneously promoting Th2 cell differentiation <i>in vitro</i>. In addition, Bregs facilitated the development of regulatory T cells (Tregs) resulting in a possible feedback cooperation to establish immune homeostasis. Moreover, the colonization of germfree wild type mice with <i>E. coli</i> but not <i>B. vulgatus</i> significantly reduced intestinal inflammatory processes in dextran sulfate sodium (DSS)-induced colitis associated with an increase induction of immune suppressive Bregs. The quantity of Bregs directly correlated with the severity of inflammation. These findings may provide new insights and therapeutic approaches for B cell-controlled treatments of microbiota-driven autoimmune disease.
Gut Bacterial Metabolite Urolithin A Decreases Actin Polymerization and Migration in Cancer Cells
2020-01-24

Scope Urolithin A (UA) is a gut‐derived bacterial metabolite from ellagic acid found in pomegranates, berries, and nuts can downregulate cell proliferation and migration. Cell proliferation and cell motility require actin reorganization, which is under control of ras‐related C3 botulinum toxin substrate 1 (Rac1) and p21 protein‐activated kinase 1 (PAK1). The present study explores whether UA can modify actin cytoskeleton in cancer cells. Methods The effect of UA on globular over filamentous actin ratio is determined utilizing Western blotting, immunofluorescence, and flow cytometry. Rac1 and PAK1 levels are measured by quantitative RT‐PCR and immunoblotting. As a result, a 24 h treatment with UA (20 μ m ) significantly decreased Rac1 and PAK1 transcript levels and activity, depolymerized actin and wound healing. The effect of UA on actin polymerization is mimicked by pharmacological inhibition of Rac1 and PAK1. The effect is also mirrored by knock down using siRNA. Conclusion UA leads to disruption of Rac1 and Pak1 activity with subsequent actin depolymerization and migration. Thus, use of dietary UA in cancer prevention or as adjuvant therapy is promising.
EPIFANY: A Method for Efficient High-Confidence Protein Inference
2020-01-24

Accurate protein inference in the presence of shared peptides is still one of the key problems in bottom-up proteomics. Most protein inference tools employing simple heuristic inference strategies are efficient but exhibit reduced accuracy. More advanced probabilistic methods often exhibit better inference quality but tend to be too slow for large data sets. Here, we present a novel protein inference method, EPIFANY, combining a loopy belief propagation algorithm with convolution trees for efficient processing of Bayesian networks. We demonstrate that EPIFANY combines the reliable protein inference of Bayesian methods with significantly shorter runtimes. On the 2016 iPRG protein inference benchmark data, EPIFANY is the only tested method that finds all true-positive proteins at a 5% protein false discovery rate (FDR) without strict prefiltering on the peptide-spectrum match (PSM) level, yielding an increase in identification performance (+10% in the number of true positives and +14% in partial AUC) compared to previous approaches. Even very large data sets with hundreds of thousands of spectra (which are intractable with other Bayesian and some non-Bayesian tools) can be processed with EPIFANY within minutes. The increased inference quality including shared peptides results in better protein inference results and thus increased robustness of the biological hypotheses generated. EPIFANY is available as open-source software for all major platforms at https://OpenMS.de/epifany.
The Systems Biology Graphical Notation: Current Status and Applications in Systems Medicine
2020-01-24

The Systems Biology Graphical Notation (SBGN) is a community standard developed to reduce ambiguity in the visual representation of biomolecular networks by providing a standardized description of sets of symbols to use. SBGN comprises three distinct but complementary languages: Process Description (PD), Entity Relationship (ER), and Activity Flow (AF). SBGN captures distinct levels of details. SBGN PD is well-suited for representing detailed sequential biochemical mechanisms, such as metabolic pathways. SBGN AF shows cascades of influences between the activities carried out by biomolecular entities (e.g., stimulation and inhibition) in signaling pathways and regulatory networks. SBGN ER represents independent interactions between features of biological entities, thereby avoiding the complexity of represented biological states and interactions. SBGN has become a well-established standard in systems biology and systems medicine. Numerous visualization tools support SBGN, which is increasingly used in many popular biological databases as well as in scientific publications. This article aims at providing an overview of SBGN and its current applications in the field of biomedicine.
Nostotrebin 6 Related Cyclopentenediones and δ-Lactones with Broad Activity Spectrum Isolated from the Cultivation Medium of the Cyanobacterium Nostoc sp. CBT1153
2020-01-24

Cyanobacteria are an interesting source of biologically active natural products, especially chemically diverse and potent protease inhibitors. On our search for inhibitors of the trypanosomal cysteine protease rhodesain, we identified the homodimeric cyclopentenedione (CPD) nostotrebin 6 (<b>1</b>) and new related monomeric, dimeric, and higher oligomeric compounds as the active substances in the medium extract of <i>Nostoc</i> sp. CBT1153. The oligomeric compounds are composed of two core monomeric structures, a trisubstituted CPD or a trisubstituted unsaturated δ-lactone. Nostotrebin 6 thus far has been the only known cyanobacterial CPD. It has been found to be active in a broad variety of assays, indicating that it might be a pan-assay interference compound (PAIN). Thus, we compared the antibacterial and cytotoxic activities as well as the rhodesain inhibition of selected compounds. Because a compound with a δ-lactone instead of a CPD core structure was equally active as nostotrebin 6, the bioactivities of these compounds seem to be based on the phenolic substructures rather than the CPD moiety. While the dimers were roughly equally potent, the monomer displayed slightly weaker activity, suggesting that the compounds show unspecific activity depending upon the number of free phenolic hydroxy groups per molecule.
Clinical Management of Squamous Cell Carcinoma of the Conjunctiva
2020-01-24

BACKGROUND Conjunctival squamous cell carcinoma is the most common non-pigmented malignancy of the ocular surface. This report illustrates the clinical management of squamous cell carcinoma of the conjunctiva. CASE REPORT A 33-year-old female was referred to our eye hospital with a tumorous lesion on the nasal bulbar conjunctiva of the right eye. A topical therapy with antibiotic and corticosteroid eye drops did not change the lesion. The conjunctival tumor was widely resected. The histopathological diagnosis suggested a squamous cell carcinoma. After resection, a treatment with topical mitomycin C (MMC) 0.02% eye drops were started 4 times daily for 14 days. Two cycles of treatment were done with a 2-week interval during which only artificial tears eye drops were administered. At the 12-month follow-up, there was no sign of recurrence. CONCLUSIONS This case illustrates the effective and successful clinical management of squamous cell carcinoma of the conjunctiva with excision and postoperative treatment with MMC 0.02% eye drops.
Correction: Single Nucleotide Polymorphisms in Thyroid Hormone Transporter Genes MCT8, MCT10 and Deiodinase DIO2 Contribute to Inter-Individual Variance of Executive Functions and Personality Traits
2020-01-24

Correction to:Single Nucleotide Polymorphisms in Thyroid Hormone Transporter Genes MCT8, MCT10 and Deiodinase DIO2 Contribute to Inter-Individual Variance of Executive Functions and Personality TraitsExp Clin Endocrinol Diabetes 2020; 128(09): 573-581DOI: 10.1055/a-1065-1786
A Short Empathy Paradigm to Assess Empathic Deficits in Schizophrenia
2020-01-24

Empathy is important for successful social interaction and maintaining relationships. Several studies detected impairments in empathic abilities in schizophrenia, with some even indicating a broader deficit in several components, including emotion recognition, perspective taking, and affective responsiveness. The aim of our study was to validate a short version of the previous empathy paradigm as a reliable and easily applicable method to assess empathic deficits in patients with schizophrenia potentially within clinical routine. To do so, we applied the short version to 30 patients (14 females) diagnosed with schizophrenia meeting the DSM-5 criteria and 30 well-matched healthy controls (14 females). The data analysis indicates a significant empathic deficit in patients due to worse performance in all three domains. We managed to replicate most of the findings of our previous study. In contrary to the previous study, significant correlations between performance in the empathy tasks and psychopathology occurred: the severity of negative symptoms was negatively associated with performance in the emotion recognition task and the affective responsiveness task. Gender did not significantly affect performance in the empathy tasks. Regarding the results, our short empathy paradigm appears to be a valid method in assessing empathic impairments in schizophrenia that may be useful in clinical routine.
A rare case of an evolutionary late and ephemeral biomineralization: tunicates with composite calcareous skeletons
2020-01-24

Abstract In contrast to almost all other invertebrate phyla that constructed biomineralized skeletons during the “Cambrian explosion” and maintained them during the entire fossil record, ascidian tunicates evolved this protective and stabilizing advantage only during the Permian, although soft-bodied representatives of this subphylum made their first appearance already in the early Cambrian. It remains enigmatic why these compound calcareous skeletons persisted only until the Late Triassic, subsequently followed by less-rigid internal skeletons from the Lower Jurassic onwards, which consist of scattered isolated spicules only. In addition to recently described aragonitic ascidian exoskeletons from the Permian and Triassic, new discoveries of similar, but colonial ascidian compound endoskeletons in the lower Carnian exhibit a short-living branch of this group, which moreover contain the first indubitable calcareous spicules. The latter are embedded in the solid endoskeleton, which is composed of polygonal aragonitic plates with smooth outer and zigzag lined inner boundaries. They consist of irregular, parallel (orthogonal), or fan-shaped (clinogonal) arrangements of acicular aragonite crystals. The following taxa are described as new: order Cassianomorpha new order with the family Cassianosomidae new family and the genus Toscanisoma new genus with the species T . multipartitum new species and T . triplicatum new species. UUID: http://zoobank.org/03555353-cdab-42e8-8e99-9bfce15fa249
Enhancing CO2-valorization usingClostridium autoethanogenumfor sustainable fuel and chemicals production
2020-01-24

Abstract Acetogenic bacteria can convert waste gases into fuels and chemicals. Design of bioprocesses for waste carbon valorization requires quantification of steady-state carbon flows. Here, steady-state quantification of autotrophic chemostats containing Clostridium autoethanogenum grown on CO 2 and H 2 revealed that captured carbon (460 ± 80 mmol/gDCW/day) had a significant distribution to ethanol (54 ± 3 mol% with a 2.4 ± 0.3 g/L titer). We were impressed with this initial result, but also observed limitations to biomass concentration and growth rate. Metabolic modelling predicted culture performance and indicated significant metabolic adjustments when compared to fermentation with CO as the carbon source. Moreover, modelling highlighted flux to pyruvate, and subsequently reduced ferredoxin, as a target for improving CO 2 and H 2 fermentation. Supplementation with a small amount of CO enabled co-utilisation with CO 2 , and enhanced CO 2 fermentation performance significantly, while maintaining an industrially relevant product profile. Additionally, the highest specific flux through the Wood-Ljungdahl pathway was observed during co-utilization of CO 2 and CO. Furthermore, the addition of CO led to superior CO 2 -valorizing characteristics (9.7 ± 0.4 g/L ethanol with a 66 ± 2 mol% distribution, and 540 ± 20 mmol CO 2 /gDCW/day). Similar industrial processes are commercial or currently being scaled up, indicating CO-supplemented CO 2 and H 2 fermentation has high potential for sustainable fuel and chemical production. This work also provides a reference dataset to advance our understanding of CO 2 gas fermentation, which can contribute to mitigating climate change.
Data for: A multicenter, prospective observational study of intraleukocytic and intraerythrocytic pigment as prognostic features in African children with falciparum malaria
2020-01-24

&lt;p&gt;This data collection was generated by a study of the prognostic significance of circulating pigment conducted by consortium of research units at five sites (Kenya, Ghana, Gabon, Gambia, Malawi). The study was part of a large multicentre prospective observational study of children admitted with falciparum malaria to SMAC (Severe Malaria in African Children clinical network). The prospective study aimed at setting up a core database to determine prognostic features in African children with severe malaria. It was the first study undertaken by the first clinical network devoted to the study of severe malaria in African children. A detailed description of the study design and participating sites was provided by Taylor T, Olola C, Valim C, et al. Standardized data collection for multi-center clinical studies of severe malaria in African children: establishing the SMAC network. Trans R Soc Trop Med Hyg. 2006;100:615–22 and Olola CH, Missinou MA, Issifou S, et al. Medical informatics in medical research—the Severe Malaria in African Children (SMAC) Network's experience. Methods Inf Med. 2006;45:483–91. &lt;/p&gt; &lt;p&gt;From December 2000 through May 2005, all children aged &lt;1 to 180 months who were suspected of having malaria and were sick enough to be hospitalized were screened with a thick blood smear for the presence of P. falciparum parasitemia. Following consent from parents/guardians, children with positive blood smears were recruited into the study. The collection contains data on patient demographics, history of present illness, clinical details at the time of assessment and laboratory investigations. &lt;/p&gt;