julilili42/papers huggingface dataset:
Healthcare professionals’ perspectives on working conditions, leadership, and safety climate: a cross-sectional study
2019-01-21

Background: Promoting patient and occupational safety are two key challenges for hospitals. When aiming to improve these two outcomes synergistically, psychosocial working conditions, leadership by hospital management and supervisors, and perceptions of patient and occupational safety climate have to be considered. Recent studies have shown that these key topics are interrelated and form a critical foundation for promoting patient and occupational safety in hospitals. So far, these topics have mainly been studied independently from each other. The present study investigated hospital staffs’ perceptions of four different topics: (1) psychosocial working conditions, (2) leadership, (3) patient safety climate, and (4) occupational safety climate. We present results from a survey in two German university hospitals aiming to detect differences between nurses and physicians. Methods: We performed a cross-sectional study using a standardized paper-based questionnaire. The survey was conducted with nurses and physicians to assess the four topics. The instruments mainly consisted of scales of the German version of the COPSOQ (Copenhagen Psychosocial Questionnaire), one scale of the Copenhagen Burnout Inventory (CBI), scales to assess leadership and transformational leadership, scales to assess patient safety climate using the Hospital Survey on Patient Safety Culture (HSPSC), and analogous items to assess occupational safety climate. Results: A total of 995 completed questionnaires out of 2512 distributed questionnaires were returned anonymously. The overall response rate was 39.6%. The sample consisted of 381 physicians and 567 nurses. We found various differences with regard to the four topics. In most of the COPSOQ and the HSPSC-scales, physicians rated psychosocial working conditions and patient safety climate more positively than nurses. With regard to occupational safety, nurses indicated higher occupational risks than physicians. Conclusions: The WorkSafeMed study combined the assessment of the four topics psychosocial working conditions, leadership, patient safety climate, and occupational safety climate in hospitals. Looking at the four topics provides an overview of where improvements in hospitals may be needed for nurses and physicians. Based on these results, improvements in working conditions, patient safety climate, and occupational safety climate are required for health care professionals in German university hospitals – especially for nurses.
Structure–Activity and Structure–Toxicity Relationships of Peptoid‐Based Histone Deacetylase Inhibitors with Dual‐Stage Antiplasmodial Activity
2019-01-21

Abstract Novel malaria intervention strategies are of great importance, given the development of drug resistance in malaria‐endemic countries. In this regard, histone deacetylases (HDACs) have emerged as new and promising malaria drug targets. In this work, we present the design, synthesis, and biological evaluation of 20 novel HDAC inhibitors with antiplasmodial activity. Based on a previously discovered peptoid‐based hit compound, we modified all regions of the peptoid scaffold by using a one‐pot multicomponent pathway and submonomer routes to gain a deeper understanding of the structure–activity and structure–toxicity relationships. Most compounds displayed potent activity against asexual blood‐stage P. falciparum parasites, with IC 50 values in the range of 0.0052–0.25 μ m and promising selectivity over mammalian cells (SI Pf 3D7/HepG2 : 170–1483). In addition, several compounds showed encouraging sub‐micromolar activity against P. berghei exo‐erythrocytic forms ( Pb EEF). Our study led to the discovery of the hit compound N ‐(2‐(benzylamino)‐2‐oxoethyl)‐ N ‐(4‐(hydroxycarbamoyl)benzyl)‐4‐isopropylbenzamide ( 2 h ) as a potent and parasite‐specific dual‐stage antiplasmodial HDAC inhibitor (IC 50 Pf 3D7=0.0052 μ m , IC 50 Pb EEF=0.016 μ m ).
Intermittent theta burst stimulation over right somatosensory larynx cortex enhances vocal pitch‐regulation in nonsingers
2019-01-21

Abstract While the significance of auditory cortical regions for the development and maintenance of speech motor coordination is well established, the contribution of somatosensory brain areas to learned vocalizations such as singing is less well understood. To address these mechanisms, we applied intermittent theta burst stimulation (iTBS), a facilitatory repetitive transcranial magnetic stimulation (rTMS) protocol, over right somatosensory larynx cortex (S1) and a nonvocal dorsal S1 control area in participants without singing experience. A pitch‐matching singing task was performed before and after iTBS to assess corresponding effects on vocal pitch regulation. When participants could monitor auditory feedback from their own voice during singing (Experiment I), no difference in pitch‐matching performance was found between iTBS sessions. However, when auditory feedback was masked with noise (Experiment II), only larynx‐S1 iTBS enhanced pitch accuracy (50–250 ms after sound onset) and pitch stability (&gt;250 ms after sound onset until the end). Results indicate that somatosensory feedback plays a dominant role in vocal pitch regulation when acoustic feedback is masked. The acoustic changes moreover suggest that right larynx‐S1 stimulation affected the preparation and involuntary regulation of vocal pitch accuracy, and that kinesthetic‐proprioceptive processes play a role in the voluntary control of pitch stability in nonsingers. Together, these data provide evidence for a causal involvement of right larynx‐S1 in vocal pitch regulation during singing.
Discovery of the Cyclic Lipopeptide Gacamide A by Genome Mining and Repair of the Defective GacA Regulator in Pseudomonas fluorescens Pf0-1
2019-01-22

Genome mining of the Gram-negative bacterium Pseudomonas fluorescens Pf0-1 showed that the strain possesses a silent NRPS-based biosynthetic gene cluster encoding a new lipopeptide; its activation required the repair of the global regulator system. In this paper, we describe the genomics-driven discovery and characterization of the associated secondary metabolite gacamide A, a lipodepsipeptide that forms a new family of Pseudomonas lipopeptides. The compound has a moderate, narrow-spectrum antibiotic activity and facilitates bacterial surface motility.
Phloem Companion Cell-Specific Transcriptomic and Epigenomic Analyses Identify MRF1, a Regulator of Flowering
2019-01-22

The phloem plays essential roles in the source-to-sink relationship and in long-distance communication, and thereby coordinates growth and development throughout the plant. Here we employed isolation of nuclei tagged in specific cell types coupled with low-input, high-throughput sequencing approaches to analyze the changes of the chromatin modifications H3K4me3 and H3K27me3 and their correlation with gene expression in the phloem companion cells (PCCs) of Arabidopsis(<i>Arabidopsis thaliana</i>) shoots in response to changes in photoperiod. We observed a positive correlation between changes in expression and H3K4me3 levels of genes that are involved in essential PCC functions, including regulation of metabolism, circadian rhythm, development, and epigenetic modifications. By contrast, changes in H3K27me3 signal appeared to contribute little to gene expression changes. These genomic data illustrate the complex gene-regulatory networks that integrate plant developmental and physiological processes in the PCCs. Emphasizing the importance of cell-specific analyses, we identified a previously uncharacterized MORN-motif repeat protein, MORN-MOTIF REPEAT PROTEIN REGULATING FLOWERING1 (MRF1), that was strongly up-regulated in the PCCs in response to inductive photoperiod. The <i>mrf1</i> mutation delayed flowering, whereas <i>MRF1</i> overexpression had the opposite effect, indicating that MRF1 acts as a floral promoter.
Between organization and spontaneity of protests: the 2010–2011 Tunisian and Egyptian uprisings
2019-01-22

This paper investigates the role of social groups in mobilizing resources for protests in repressive contexts. In particular, it examines the impact of organizations and informal groups on individual engagement in the protests developed in 2010 in Tunisia and in 2011 in Egypt. The empirical analysis draws on the following data sources: the second wave of the Arab Barometer (2010–2011), two focus groups in Egypt conducted between 2011 and 2015 with members of trade unions and of Popular Committees who had participated in the 2011 protests in Egypt, eight semi-structured interviews conducted in 2017 to workers in Tunisia who had engaged in the 2010–2011 protests, and interviews conducted in January and February 2011 to 100 women in Tunisia within a study tackling police violence against women during the Tunisian uprisings.Findings show that both in Egypt and Tunisia protests were neither spontaneous nor fully organized as formal organizations and informal and spontaneous groups strictly interconnected in sustaining protests. In Egypt, established Islamic charity networks provided the structural basis for Popular Committees to engage in the 2011 protests and the initially spontaneous workers' groups, institutionalized through the legalization of EFITU, were crucial for national wide protests occurred throughout 2011. In Tunisia, the major trade union UGTT was essential for mobilizing workers in the initial stages of protests but was backed by informal and spontaneous groups of workers during the process of protest diffusion.Results remark that the 2010–2011 Tunisian and Egyptian uprisings were therefore well-grounded on intermediate mobilizing structures capable to survive in the interstices of an authoritarian context. Findings suggest to consider that, in repressive context, spontaneous groups and more established and formal organizations continuously switch from one form to another, overlap, and transform themselves faster than they would do in democratic contexts.
The Polycyclic Polyprenylated Acylphloroglucinol Antibiotic PPAP 23 Targets the Membrane and Iron Metabolism in Staphylococcus aureus
2019-01-22

Recently, a series of endo-type B polycyclic polyprenylated acylphloroglucinols (PPAP) derivatives with high antimicrobial activities were chemically synthesized. One of the derivatives, PPAP 23, which showed high antimicrobial activity and low cytotoxicity, was chosen for further investigation of its bactericidal profiles and mode of action. PPAP 23 showed a better efficacy in killing methicillin resistant <i>Staphylococcus aureus</i> (MRSA) and decreasing the metabolic activity of 5-day-old biofilm cells than vancomycin. Moreover, <i>S. aureus</i> did not appear to develop resistance against PPAP 23. The antimicrobial mechanism of PPAP 23 was investigated by RNA-seq combined with phenotypic and biochemical approaches. RNA-seq suggested that PPAP 23 signaled iron overload to the bacterial cells because genes involved in iron transport were downregulated and iron storage gene was upregulated by PPAP 23. PPAP 23 affected the membrane integrity but did not induce pore formation; it inhibited bacterial respiration. PPAP 23 preferentially inhibited Fe-S cluster enzymes; it has a mild iron chelating activity and supplementation of exogenous iron attenuated its antimicrobial activity. PPAP 23 was more effective in inhibiting the growth of <i>S. aureus</i> under iron-restricted condition. The crystal structure of a benzylated analog of PPAP 23 showed a highly defined octahedral coordination of three PPAP ligands around a Fe (3+) core. This suggests that PPAPs are generally capable of iron chelation and are able to form defined stable complexes. PPAP 23 was found to induce reactive oxygen species (ROS) and oxidative stress. Fluorescence microscopic analysis showed that PPAP 23 caused an enlargement of the bacterial cells, perturbed the membrane, and dislocated the nucleoid. Taken together, we postulate that PPAP 23 interacts with the cytoplasmic membrane with its hydrophobic pocket and interferes with the iron metabolism to exert its antimicrobial activity in <i>Staphylococcus aureus</i>.
Altered Processing of Visual Food Stimuli in Adolescents with Loss of Control Eating
2019-01-22

Loss of control eating (LOC) constitutes a common eating pathology in childhood and adolescence. Models developed for adult patients stress a biased processing of food-related stimuli as an important maintaining factor. To our knowledge, however, no EEG study to date investigated the processing of visual food stimuli in children or adolescents with LOC. Adolescents with at least one self-reported episode of LOC in the last four weeks and a matched control group completed a modified Go/NoGo task, with a numerical target or non-target stimulus being presented on one side of the screen and an irrelevant high-calorie food or neutral stimulus being presented on the opposite side. Mean P3 amplitudes were analyzed. In Go trials, the LOC group’s mean P3 amplitudes were comparable irrespective of distractor category, while for NoGo trials, mean P3 amplitudes were significantly higher when the distractor was a high-calorie food stimulus. This pattern was reversed in the control group. Results are interpreted in light of Gray’s reinforcement sensitivity theory. They might reflect altered processes of behavioral inhibition in adolescents with LOC upon confrontation with visual food stimuli.
Nitrogen Supply Drives Senescence-Related Seed Storage Protein Expression in Rapeseed Leaves
2019-01-22

In general, yield and fruit quality strongly rely on efficient nutrient remobilization during plant development and senescence. Transcriptome changes associated with senescence in spring oilseed rape grown under optimal nitrogen supply or mild nitrogen deficiency revealed differences in senescence and nutrient mobilization in old lower canopy leaves and younger higher canopy leaves. Having a closer look at this transcriptome analyses, we identified the major classes of seed storage proteins (SSP) to be expressed in vegetative tissue, namely leaf and stem tissue. Expression of SSPs was not only dependent on the nitrogen supply but transcripts appeared to correlate with intracellular H2O2 contents, which functions as well-known signaling molecule in developmental senescence. The abundance of SSPs in leaf material transiently progressed from the oldest leaves to the youngest. Moreover, stems also exhibited short-term production of SSPs, which hints at an interim storage function. In order to decipher whether hydrogen peroxide also functions as a signaling molecule in nitrogen deficiency-induced senescence, we analyzed hydrogen peroxide contents after complete nitrogen depletion in oilseed rape and Arabidopsis plants. In both cases, hydrogen peroxide contents were lower in nitrogen deficient plants, indicating that at least parts of the developmental senescence program appear to be suppressed under nitrogen deficiency.
Platelet-neutrophil aggregates promote skin pathology in psoriasis
2019-01-22

Abstract Psoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental in vivo model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in vivo ameliorated disease severity significantly, indicating that the intimate relationship of PMNs and platelets may be relevant for psoriasis pathology and disease severity, and potentially for psoriasis-associated cardiovascular comorbidities. Key points Human neutrophils in psoriasis patient blood show a distinct ‘platelet signature’ of surface antigens Platelets congregate with neutrophils in psoriatic skin lesions Circulating platelets contribute to psoriasis skin pathology
The RANO Leptomeningeal Metastasis Group proposal to assess response to treatment: lack of feasibility and clinical utility and a revised proposal
2019-01-23

Assessing response of LM by MRI remains challenging. Central imaging review is therefore indispensable for clinical trials. Based on the present results, we propose a new, simplified scorecard that will require validation using a similar approach as pursued here. The main challenges are to define measurable versus nonmeasurable (target) lesions and measures of change that allow assessment of response.
Cell type composition and circuit organization of neocortical radial clones
2019-01-23

Summary Excitatory neurons arising from a common progenitor establish radially-oriented clonal units in the neocortex which have been proposed to serve as elementary information processing modules. To characterize the cell types and circuit diagram within these clonal units, we performed single-cell RNA-sequencing and multi-cell patch clamp recordings of neurons derived from Nestin -positive progenitors. We found that radial clones do not appear to be fate-restricted, but instead individual clones are composed of a random sampling of the transcriptomic cell types present in a particular cortical area. The effect of lineage on synaptic connectivity depends on the type of connection tested: pairs of clonally related neurons were more likely to be connected vertically, across cortical layers, but not laterally within the same layer, compared to unrelated pairs. We propose that integration of vertical input from related neurons with lateral input from unrelated neurons may represent a developmentally programmed motif for assembling neocortical circuits.
The number of spaced-word matches between twoDNAsequences as a function of the underlying pattern weight
2019-01-23

Abstract We study the number N k of (spaced) word matches between pairs of evolutionarily related DNA sequences depending on the word length or pattern weight k , respectively. We show that, under the Jukes-Cantor model, the number of substitutions per site that occurred since two sequences evolved from their last common ancestor, can be esti-mated from the slope of a certain function of N k . Based on these considerations, we implemented a software program for alignment-free sequence comparison called Slope-SpaM . Test runs on simulated sequence data show that Slope-SpaM can estimate phylogenetic dis-tances with high accuracy for up to around 0.5 substitutions per po-sitions. The statistical stability of our results is improved if spaced words are used instead of contiguous k -mers. Unlike previous methods that are based on the number of (spaced) word matches, our approach can deal with sequences that share only local homologies.
Inhibition of fatty acid desaturation impairs cuticle differentiation in Drosophila melanogaster
2019-01-23

Abstract Previously, we showed that inhibition of the activity of fatty acid desaturases (Desat) perturbs signalling of the developmental timing hormone ecdysone in the fruit fly Drosophila melanogaster . To understand the impact of this effect on cuticle differentiation, a process regulated by ecdysone, we analysed the cuticle of D. melanogaster larvae fed with the Desat inhibitor CA10556. In these larvae, the expression of most of the key cuticle genes is normal or slightly elevated at day one of CA10556 feeding. As an exception, expression of twdlM coding for a yet uncharacterised cuticle protein is completely suppressed. The cuticle of these larvae appears to be normal at the morphological level. However, these animals are sensitive to desiccation, a trait that according to our data, among others, may be associated with reduced TwdlM amounts. At day two of CA10556 feeding, expression of most of the cuticle genes tested including twdlM is suppressed. Expression of cpr47Eb coding for a chitin‐binding protein is, by contrast, highly elevated suggesting that Cpr47Eb participates at a specific compensation program. Overall, the cuticle of these larvae is thinner than the cuticle of control larvae. Taken together, lipid desaturation is necessary for a coordinated deployment of a normal cuticle differentiation program.
Complete Genome Sequence of the Putative Phosphonate Producer Streptomyces sp. Strain I6, Isolated from Indonesian Mangrove Sediment
2019-01-23

Streptomyces sp. strain I6 is a novel strain isolated from an Indonesian mangrove sediment sample. Bioinformatic analysis of the genome sequence of Streptomyces sp. I6 revealed 23 biosynthetic gene clusters.
The Last Copper Century: Southwest China and the Coin Economy (1705–1808)
2019-01-23

Abstract Over the last millennium, the priority for imperial China’s parallel bimetallic monetary system shifted from copper cash to silver bullion, a development that gained momentum with the influx of New World silver during the sixteenth century. This trend was altered when the Qing government increased copper production in the Southwest, thus inaugurating China’s last copper century around 1705. This study focuses on those provinces where the wealth of China’s copper economy was created: Yunnan, where copper for the metropolitan mints in Beijing was mined under relatively strict governmental control; and especially Sichuan, which maintained China’s largest provincial mint and favored a more flexible cooperation between state and private structures. In these provinces, the interrelations between mining and minting can be observed most closely, the copper century lasted longer and showed a deeper impact, and the symptoms of its final crisis, like counterfeiting or coin debasement, became most apparent. This study aims to reassess our understanding of Chinese mint-metal mining and copper-coin production in practice and theory. It shows the importance of the internal market in huge land empires like China but also—through its interrelation with silver in the bimetallic system—its deep involvement in an increasingly integrated global economy.