julilili42/papers huggingface dataset:
Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
2021-04-15

Abstract Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I2 = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2 = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.
Overview of digital health teaching courses in medical education in Germany in 2020
2021-04-15

Objective: The digitalization of the healthcare system poses new challenges for physicians. Thus, the relevance of learning digital competencies (DiCo), such as dealing with data sets, apply telemedicine or using apps, is already growing in medical education. DiCo should be clearly separated from digitized teaching formats, which have been increasingly used since the COVID 19 pandemic. This article outlines the faculties in Germany where DiCo are already integrated into medical education. Methods: Courses with DiCo as teaching content were collected by a literature research on Pubmed and Google as well as by contacting all dean's offices and other persons responsible for teaching at German medical faculties. The courses were summarized in a table. Results: In a first survey, 16 universities were identified that offer courses on DiCo. In the elective area at the universities, 17 courses and in the compulsory area eight courses could be identified. The scope and content of the courses diverged between compulsory curricula, integrated courses of different lengths, and elective courses that are one-time or longitudinally integrated. The topics taught are heterogeneous and include fundamentals of medical informatics such as data management on the one hand and a collection of e.g. ethics, law, apps, artificial intelligence, telemedicine and robotics on the other hand. Conclusion: Currently, only some German medical faculties offer courses on DiCo. These courses vary in scope and design. They are frequently part of the elective curriculum and only reach some of the students. The possibility of embedding DiCo in the already existing cross-sectional area appears limited. In view of the ongoing digitalization of healthcare, it is necessary to make future courses on DiCo accessible to all medical students. In order to drive this expansion forward, the implementation of the new learning objectives catalogue, in which DiCo are integrated, a network formation, a teaching qualification as well as the involvement of students is recommended.
Drug Repurposing: A Review of Old and New Antibiotics for the Treatment of Malaria: Identifying Antibiotics with a Fast Onset of Antiplasmodial Action
2021-04-15

Malaria is one of the most life-threatening infectious diseases and constitutes a major health problem, especially in Africa. Although artemisinin combination therapies remain efficacious to treat malaria, the emergence of resistant parasites emphasizes the urgent need of new alternative chemotherapies. One strategy is the repurposing of existing drugs. Herein, we reviewed the antimalarial effects of marketed antibiotics, and described in detail the fast-acting antibiotics that showed activity in nanomolar concentrations. Antibiotics have been used for prophylaxis and treatment of malaria for many years and are of particular interest because they might exert a different mode of action than current antimalarials, and can be used simultaneously to treat concomitant bacterial infections.
The EXTraS project: Exploring the X-ray transient and variable sky
2021-04-15

Temporal variability in flux and spectral shape is ubiquitous in the X-ray sky and carries crucial information about the nature and emission physics of the sources. The EPIC instrument on board the XMM-Newton observatory is the most powerful tool for studying variability even in faint sources. Each day, it collects a large amount of information about hundreds of new serendipitous sources, but the resulting huge (and growing) dataset is largely unexplored in the time domain. The project called Exploring the X-ray transient and variable sky (EXTraS) systematically extracted all temporal domain information in the XMM-Newton archive. This included a search and characterisation of variability, both periodic and aperiodic, in hundreds of thousands of sources spanning more than eight orders of magnitude in timescale and six orders of magnitude in flux, and a search for fast transients that were missed by standard image analysis. All results, products, and software tools have been released to the community in a public archive. A science gateway has also been implemented to allow users to run the EXTraS analysis remotely on recent XMM datasets. We give details on the new algorithms that were designed and implemented to perform all steps of EPIC data analysis, including data preparation, source and background modelling, generation of time series and power spectra, and search for and characterisation of different types of variabilities. We describe our results and products and give information about their basic statistical properties and advice on their usage. We also describe available online resources. The EXTraS database of results and its ancillary products is a rich resource for any kind of investigation in almost all fields of astrophysics. Algorithms and lessons learnt from our project are also a very useful reference for any current and future experiment in the time domain.
Nep1-like proteins as a target for plant pathogen control
2021-04-15

The lack of efficient methods to control the major diseases of crops most important to agriculture leads to huge economic losses and seriously threatens global food security. Many of the most important microbial plant pathogens, including bacteria, fungi, and oomycetes, secrete necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs), which critically contribute to the virulence and spread of the disease. NLPs are cytotoxic to eudicot plants, as they disturb the plant plasma membrane by binding to specific plant membrane sphingolipid receptors. Their pivotal role in plant infection and broad taxonomic distribution makes NLPs a promising target for the development of novel phytopharmaceutical compounds. To identify compounds that bind to NLPs from the oomycetes Pythium aphanidermatum and Phytophthora parasitica , a library of 587 small molecules, most of which are commercially unavailable, was screened by surface plasmon resonance. Importantly, compounds that exhibited the highest affinity to NLPs were also found to inhibit NLP-mediated necrosis in tobacco leaves and Phytophthora infestans growth on potato leaves. Saturation transfer difference-nuclear magnetic resonance and molecular modelling of the most promising compound, anthranilic acid derivative, confirmed stable binding to the NLP protein, which resulted in decreased necrotic activity and reduced ion leakage from tobacco leaves. We, therefore, confirmed that NLPs are an appealing target for the development of novel phytopharmaceutical agents and strategies, which aim to directly interfere with the function of these major microbial virulence factors. The compounds identified in this study represent lead structures for further optimization and antimicrobial product development.
Sleep strengthens integration of spatial memory systems
2021-04-15

Spatial memory comprises different representational systems that are sensitive to different environmental cues, like proximal landmarks or local boundaries. Here we examined how sleep affects the formation of a spatial representation integrating landmark-referenced and boundary-referenced representations. To this end, participants ( n = 42) were familiarized with an environment featuring both a proximal landmark and a local boundary. After nocturnal periods of sleep or wakefulness and another night of sleep, integration of the two representational systems was tested by testing the participant's flexibility to switch from landmark-based to boundary-based navigation in the environment, and vice versa. Results indicate a distinctly increased flexibility in relying on either landmarks or boundaries for navigation, when familiarization to the environment was followed by sleep rather than by wakefulness. A second control study ( n = 45) did not reveal effects of sleep (vs. wakefulness) on navigation in environments featuring only landmarks or only boundaries. Thus, rather than strengthening isolated representational systems per se, sleep presumably through forming an integrative representation, enhances flexible coordination of representational subsystems.
Neutral R3PAuGe9(Hyp)3 (R=Et, nPr, iPr, nBu, tBu, Cy) (Hyp=Si(SiMe3) Clusters give new insights into the ligand strength of the metalloid [Ge9(Hyp)3]− cluster
2021-04-15

Abstract We present new insights into the ligand strength of the metalloid [Ge 9 (Hyp) 3 ] − cluster (Hyp=Si(SiMe 3 ) 3 ) alongside novel neutral Ge 9 clusters of the composition R 3 PAuGe 9 (Hyp) 3 (R=Et, n Pr, i Pr, n Bu, t Bu, Cy). These clusters are synthesized in good yields from KGe 9 (Hyp) 3 and R 3 PAuCl. Further experiments with these new clusters show that the ligand strength of [Ge 9 (Hyp) 3 ] − is in between aryl and alkyl phosphines.
Adipose tissue distribution from body MRI is associated with cross-sectional and longitudinal brain age in adults
2021-04-15

Abstract There is an intimate body-brain connection in ageing, and obesity is a key risk factor for poor cardiometabolic health and neurodegenerative conditions. Although research has demonstrated deleterious effects of obesity on brain structure and function, the majority of studies have used conventional measures such as waist-to-hip ratio, waist circumference, and body mass index. While sensitive to gross features of body composition, such global anthropomorphic features fail to describe regional differences in body fat distribution and composition, and to determine visceral adiposity, which is related to a range of metabolic conditions. In this mixed cross-sectional and longitudinal design (interval mean and standard deviation = 19.7 ± 0.5 months), including 790 healthy individuals (mean (range) age = 46.7 (18-94) years, 53% women), we investigated cross-sectional body magnetic resonance imaging (MRI, n = 286) measures of adipose tissue distribution in relation to longitudinal brain structure using MRI-based morphometry and diffusion tensor imaging (DTI). We estimated tissue-specific brain age at two time points and performed Bayesian multilevel modelling to investigate the associations between adipose measures at follow-up and brain age gap (BAG) at baseline and follow-up. We also tested for interactions between BAG and both time and age on each adipose measure. The results showed credible associations between T1-based BAG and liver fat, muscle fat infiltration (MFI), and weight-to-muscle ratio (WMR), indicating older-appearing brains in people with higher measures of adipose tissue. Longitudinal evidence supported interaction effects between time and MFI and WMR on T1-based BAG, indicating accelerated ageing over the course of the study period in people with higher measures of adipose tissue. The results show that specific measures of fat distribution are associated with brain ageing and that different compartments of adipose tissue may be differentially linked with increased brain ageing, with potential to identify key processes involved in age-related transdiagnostic disease processes.
Phrasal Learning Is a Horse Apiece: No Recognition Memory Advantages for Idioms in L1 and L2 Adult Learners
2021-04-15

Native (L1) and to some extent non-native (L2) speakers have shown processing advantages for idioms compared to novel literal phrases, and there is limited evidence that this advantage also extends to memory in L1 children. This study investigated whether these advantages generalize to recognition memory in adults. It employed a learning paradigm to test whether there is a recognition memory advantage for idioms compared to literal phrases in adult L1 and L2 learners considering both form and meaning recognition. Additionally, we asked whether the presence of unfamiliar vocabulary interferes with phrasal learning by looking at recall of such unfamiliar words. When encountering new idioms, L2 learners often must cope with both figurative meaning and unfamiliar vocabulary. While single word meaning need not interfere with idiomatic meaning, it is a building block for the meaning of literal phrases. In Experiment 1, L2 learners showed equal recall for the form and meaning of literal and idiomatic phrases in which either all words were highly familiar, or one word was unfamiliar. However, unfamiliar words decreased overall recognition and were also remembered significantly better in literal compared to idiomatic phrases. In Experiment 2, L1 speakers also showed no recall differences between phrase types, but they displayed a trending increase in recognition in the presence of unfamiliar words. We conclude that there is no inherent recognition memory advantage for idioms based on figurativeness alone, and word- and phrasal meaning interact differently in learner groups.
Phosphorylation of phosphoglucomutase 1 on a peripheral site tunes its activity to regulate glycogen metabolism
2021-04-15

Abstract Regulation of glycogen metabolism is of vital importance in organisms of all three kingdoms of life. Although the pathways involved in glycogen synthesis and degradation are well known, many regulatory aspects around the metabolism of this polysaccharide remain undeciphered. Here, we used the unicellular cyanobacterium Synechocystis as a model to investigate how glycogen metabolism is regulated in nitrogen-starved dormant cells, which entirely rely on glycogen catabolism to resume growth upon nitrogen repletion. We identified phosphoglucomutase 1 (PGM1) as a key regulatory point in glycogen metabolism, and post-translational modification as an essential mechanism for controlling its activity. We could show that PGM1 is phosphorylated at a peripheral residue (Ser 47) during nitrogen starvation, which inhibits its activity. Inactivation of PGM1 by phosphorylation at Ser 47 prevents premature degradation of the glycogen stores and appears to be essential for survival of Synechocystis in the dormant state. Remarkably, this regulatory mechanism seems to be evolutionary conserved in PGM1 enzymes, from bacteria to humans. Significance statement In this study, we identified phosphoglucomutase 1 (PGM1) as a central metabolic valve that regulates the utilization of the glycogen reserves. We showed that post-translational modification of PGM1 via phosphorylation at a peripheral residue is a key, evolutionary-conserved regulatory mechanism that controls PGM1 activity and the mobilization of the glycogen stores.
Genome-scale modeling ofPseudomonas aeruginosaPA14 unveils its broad metabolic capabilities and role of metabolism in drug potentiation
2021-04-15

Abstract P. aeruginosa is an opportunistic human pathogen that is one of the leading causes of hospital-acquired infections. We have developed an updated genome-scale model (GEM) of Pseudomonas aeruginosa PA14 for systems-study of the pathogen. We used both automated and semi-manual approaches to reconstruct and curate the model. After an extensive literature research, we added organism-specific reactions (e.g., phenazine transport and redox metabolism, cofactor metabolism, carnitine metabolism, oxalate production, etc.) to the model. This effort led to a highly curated, three-compartment, and mass-and-charge balanced BiGG model of PA14 that contains 1509 genes, 1779 metabolic reactions and 1151 unique metabolites. The model ( i SD1509) has the largest genome coverage of P. aeruginosa PA14 to date with 424 more genes than the previous model (iPau1129). It is also the most accurate with prediction accuracies as high as 92.4% (for gene essentiality) and 93.5% (for substrate utilization). The model simulates growth in both aerobic and anaerobic conditions. It predicts the biosynthesis of the virulence factor phenazine as a process for the pathogen to grow in low-oxygen environment. Further, a mechanism for the overproduction of a drug susceptibility biomarker (gluconate) can be elucidated by the principles of optimal growth. Finally, the model also simulates drug activity potentiation and protection by fumarate and glyoxylate, respectively, and provides mechanistic explanations for these processes. Overall, i SD1509 can be utilized to decipher the metabolic mechanisms associated with virulence and antibiotic susceptibility of P. aeruginosa PA14 to aid in the development of effective intervention strategies.
The Impact of Shape-Based Cue Discriminability on Attentional Performance
2021-04-15

With rapidly developing technology, visual cues became a powerful tool for deliberate guiding of attention and affecting human performance. Using cues to manipulate attention introduces a trade-off between increased performance in cued, and decreased in not cued, locations. For higher efficacy of visual cues designed to purposely direct user’s attention, it is important to know how manipulation of cue properties affects attention. In this verification study, we addressed how varying cue complexity impacts the allocation of spatial endogenous covert attention in space and time. To gradually vary cue complexity, the discriminability of the cue was systematically modulated using a shape-based design. Performance was compared in attended and unattended locations in an orientation-discrimination task. We evaluated additional temporal costs due to processing of a more complex cue by comparing performance at two different inter-stimulus intervals. From preliminary data, attention scaled with cue discriminability, even for supra-threshold cue discriminability. Furthermore, individual cue processing times partly impacted performance for the most complex, but not simpler cues. We conclude that, first, cue complexity expressed by discriminability modulates endogenous covert attention at supra-threshold cue discriminability levels, with increasing benefits and decreasing costs; second, it is important to consider the temporal processing costs of complex visual cues.
Using a Back Exoskeleton During Industrial and Functional Tasks—Effects on Muscle Activity, Posture, Performance, Usability, and Wearer Discomfort in a Laboratory Trial
2021-04-16

Objective To investigate the effect of using a passive back-support exoskeleton (Laevo V2.56) on muscle activity, posture, heart rate, performance, usability, and wearer comfort during a course of three industrial tasks (COU; exoskeleton worn, turned-on), stair climbing test (SCT; exoskeleton worn, turned-off), timed-up-and-go test (TUG; exoskeleton worn, turned-off) compared to no exoskeleton. Background Back-support exoskeletons have the potential to reduce work-related physical demands. Methods Thirty-six men participated. Activity of erector spinae (ES), biceps femoris (BF), rectus abdominis (RA), vastus lateralis (VL), gastrocnemius medialis (GM), trapezius descendens (TD) was recorded by electromyography; posture by trunk, hip, knee flexion angles; heart rate by electrocardiography; performance by time-to-task accomplishment (s) and perceived task difficulty (100-mm visual analogue scale; VAS); usability by the System Usability Scale (SUS) and all items belonging to domains skepticism and user-friendliness of the Technology Usage Inventory; wearer comfort by the 100-mm VAS. Results During parts of COU, using the exoskeleton decreased ES and BF activity and trunk flexion, and increased RA, GM, and TD activity, knee and hip flexion. Wearing the exoskeleton increased time-to-task accomplishment of SCT, TUG, and COU and perceived difficulty of SCT and TUG. Average SUS was 75.4, skepticism 11.5/28.0, user-friendliness 18.0/21.0, wearer comfort 31.1 mm. Conclusion Using the exoskeleton modified muscle activity and posture depending on the task applied, slightly impaired performance, and was evaluated mildly uncomfortable. Application These outcomes require investigating the effects of this passive back-supporting exoskeleton in longitudinal studies with longer operating times, providing better insights for guiding their application in real work settings.