julilili42/papers huggingface dataset:
PINK1 deficiency impairs adult neurogenesis of dopaminergic neurons
2021-03-23

Abstract Recent evidence suggests neurogenesis is on-going throughout life but the relevance of these findings for neurodegenerative disorders such as Parkinson’s disease (PD) is poorly understood. Biallelic PINK1 mutations cause early onset, Mendelian inherited PD. We studied the effect of PINK1 deficiency on adult neurogenesis of dopaminergic (DA) neurons in two complementary model systems. Zebrafish are a widely-used model to study neurogenesis in development and through adulthood. Using EdU analyses and lineage-tracing studies, we first demonstrate that a subset of ascending DA neurons and adjacent local-projecting DA neurons are each generated into adulthood in wild type zebrafish at a rate that decreases with age. Pink1-deficiency impedes DA neurogenesis in these populations, most significantly in early adult life. Pink1 already exerts an early effect on Th1 + progenitor cells rather than on differentiated DA neurons only. In addition, we investigate the effect of PINK1 deficiency in a human isogenic organoid model. Global neuronal differentiation in PINK1-deficient organoids and isogenic controls is similar, but PINK1-deficient organoids display impeded DA neurogenesis. The observation of impaired adult dopaminergic neurogenesis in Pink1 deficiency in two complementing model systems may have significant consequences for future therapeutic approaches in human PD patients with biallelic PINK1 mutations.
Limitations and opportunities in the pharmacotherapy of ciliopathies
2021-03-23

Ciliopathies are a family of rather diverse conditions, which have been grouped based on the finding of altered or dysfunctional cilia, potentially motile, small cellular antennae extending from the surface of postmitotic cells. Cilia-related disorders include embryonically arising conditions such as Joubert, Usher or Kartagener syndrome, but also afflictions with a postnatal or even adult onset phenotype, i.e. autosomal dominant polycystic kidney disease. The majority of ciliopathies are syndromic rather than affecting only a single organ due to cilia being found on almost any cell in the human body. Overall ciliopathies are considered rare diseases. Despite that, pharmacological research and the strive to help these patients has led to enormous therapeutic advances in the last decade. In this review we discuss new treatment options for certain ciliopathies, give an outlook on promising future therapeutic strategies, but also highlight the limitations in the development of therapeutic approaches of ciliopathies.
Microellipsometry study of plasmonic properties of metal–insulator–metal structures with ordered lattices of nanoparticles
2021-03-23

Microellipsometric investigations of metal–insulator–metal (MIM) structures with regular square lattices of nanocylinders as one metallic layer are presented together with a theoretical description of all dipolar interactions in such a system. A comparison between the theoretical and experimental results is made, which clearly demonstrates the influence of surface plasmon on the optical properties of such MIM systems. The hybridization of localized and surface plasmon modes is revealed.
Sensitivity and resolution improvement for in-vivo magnetic resonance current density imaging (MRCDI) of the human brain
2021-03-23

ABSTRACT Purpose Magnetic resonance current density imaging (MRCDI) combines MR brain imaging with the injection of time-varying weak currents (1-2 mA) to assess the current flow pattern in the brain. However, the utility of MRCDI is still hampered by low measurement sensitivity and poor image quality. Methods We recently introduced a multi-gradient-echo-based MRCDI approach that has the hitherto best documented efficiency. We now advanced our MRCDI approach in three directions and performed phantom and in-vivo human brain experiments for validation: First, we verified the importance of enhanced spoiling and optimize it for imaging of the human brain. Second, we improved the sensitivity and spatial resolution by using acquisition weighting. Third, we added navigators as a quality control measure for tracking physiological noise. Combining these advancements, we tested our optimized MRCDI method by using 1 mA transcranial electrical stimulation (TES) currents injected via two different electrode montages in five subjects. Results For a session duration of 4:20 min, the new MRCDI method was able to detect magnetic field changes caused by the TES current flow at a sensitivity level of 84 pT, representing in a twofold increase relative to our original method. Comparing both methods to current flow simulations based on personalized head models demonstrated a consistent increase in the coefficient of determination of Δ R 2 =0.12 for the current-induced magnetic fields and Δ R 2 =0.22 for the current flow reconstructions. Interestingly, some of the simulations still clearly deviated from the measurements despite of the strongly improved measurement quality. This suggests that MRCDI can reveal useful information for the improvement of head models used for current flow simulations. Conclusion The advanced method strongly improves the sensitivity and robustness of MRCDI and is an important step from proof-of-concept studies towards a broader application of MRCDI in clinical and basic neuroscience research.
Approaches to ‘vulnerability’ in eight European disaster management systems
2021-03-24

While social vulnerability in the face of disasters has received increasing academic attention, relatively little is known about the extent to which that knowledge is reflected in practice by institutions involved in disaster management. This study charts the practitioners’ approaches to disaster vulnerability in eight European countries: Belgium; Estonia; Finland; Germany; Hungary; Italy; Norway; and Sweden. It draws on a comparative document analysis and 95 interviews with disaster managers and reveals significant differences across countries in terms of the ontology of vulnerability, its sources, reduction strategies, and the allocation of related duties. To advance the debate and provide conceptual clarity, we put forward a heuristic model to facilitate different understandings of vulnerability along the dimensions of human agency and technological structures as well as social support through private relations and state actors. This could guide risk analysis of and planning for major hazards and could be adapted further to particular types of disasters.
Measuring Cognitive Load Using In-Game Metrics of a Serious Simulation Game
2021-03-24

Serious games have become an important tool to train individuals in a range of different skills. Importantly, serious games or gamified scenarios allow for simulating realistic time-critical situations to train and also assess individual performance. In this context, determining the user’s cognitive load during (game-based) training seems crucial for predicting performance and potential adaptation of the training environment to improve training effectiveness. Therefore, it is important to identify in-game metrics sensitive to users’ cognitive load. According to Barrouillets’ time-based resource-sharing model, particularly relevant for measuring cognitive load in time-critical situations, cognitive load does not depend solely on the complexity of actions but also on temporal aspects of a given task. In this study, we applied this idea to the context of a serious game by proposing in-game metrics for workload prediction that reflect a relation between the time during which participants’ attention is captured and the total time available for the task at hand. We used an emergency simulation serious game requiring management of time-critical situations. Forty-seven participants completed the emergency simulation and rated their workload using the NASA-TLX questionnaire. Results indicated that the proposed in-game metrics yielded significant associations both with subjective workload measures as well as with gaming performance. Moreover, we observed that a prediction model based solely on data from the first minutes of the gameplay predicted overall gaming performance with a classification accuracy significantly above chance level and not significantly different from a model based on subjective workload ratings. These results imply that in-game metrics may qualify for a real-time adaptation of a game-based learning environment.
Digital humanities, knowledge complexity, and the five ‘aporias’ of digital research
2021-03-24

Abstract This article introduces a frame of reference for understanding the fundamental challenges that inform digital humanities as an interdisciplinary research area between arts, humanities, information, and computer science. Its conclusions are based upon the evidence base developed within an EU-funded collaboration known as Knowledge Complexity, or KPLEX for short (www.kplex-project.eu), in particular via the project’s thirty-eight linked interviews about big data research. When viewed from the perspective of the digital humanities, five distinct points of ‘aporia’ with a significant impact on digital humanities (DH) appear in this corpus, places where the interviewees explicitly or tacitly expose gulfs between the epistemic cultures that contribute to DH and that create tensions between these disciplines, even as they seek to collaborate. This article will explore these areas of apparent irreconcilability, and conclude with a series of reflections on how digital humanities researchers might build upon their unique competency profile to negotiate within these critical conversations, in particular in the framework of the emerging subfield of critical digital humanities.
Suspended Particulate Matter—A Source or Sink for Chemical Mixtures of Organic Micropollutants in a Small River under Baseflow Conditions?
2021-03-24

Suspended particulate matter (SPM) plays an important role in the fate of organic micropollutants in rivers during rain events, when sediments are remobilized and turbid runoff components enter the rivers. Under baseflow conditions, the SPM concentration is low and the contribution of SPM-bound contaminants to the overall risk of organic contaminants in rivers is assumed to be negligible. To challenge this assumption, we explored if SPM may act as a source or sink for all or specific groups of organic chemicals in a small river. The concentrations of over 600 contaminants and the mixture effects stemming from all chemicals in <i>in vitro</i> bioassays were measured for river water, SPM, and the surface sediment after solid-phase extraction or exhaustive solvent extraction. The bioavailable fractions of chemicals and mixture effects were estimated after passive equilibrium sampling of enriched SPM slurries and sediments in the lab. Dissolved compounds dominated the total chemical burden in the water column (water plus SPM) of the river, whereas SPM-bound chemicals contributed up to 46% of the effect burden even if the SPM concentration in rivers was merely 1 mg/L. The equilibrium between water and SPM was still not reached under low-flow conditions with SPM as a source of water contamination. The ratios of SPM-associated to sediment-associated neutral and hydrophobic chemicals as well as the ratios of the mixture effects expressed as bioanalytical equivalent concentrations were close to 1, suggesting that the surface sediment can be used as a proxy for SPM under baseflow conditions when the sampling of a large amount of water to obtain sufficient SPM cannot be realized.
Weak coordination between leaf drought tolerance and proxy traits in herbaceous plants
2021-03-24

Abstract Increased drought is predicted to have a major impact on plant performance under environmental change. Yet leaf hydraulic traits directly related to drought tolerance, such as leaf turgor loss point ( π tlp ), are under‐represented in trait‐based studies and have been largely overlooked within the main frameworks evaluating trait–trait coordination and trade‐offs—the leaf economics spectrum (LES) and the global spectrum of plant form and function. Using 122 herbaceous species from the Central European temperate grasslands, we investigated (a) the coordination between π tlp and traits often used as proxies for drought tolerance, namely SLA, leaf area (LA), leaf dry matter content (LDMC), leaf thickness (LT), plant height and intrinsic water use efficiency (iWUE); (b) whether the strength of the trait–trait relationships differed across plant functional types (PFTs: graminoids and forbs) and depended on species phylogeny; and (c) whether single or multiple traits, combined with either PFTs or phylogenetic relatedness, provide a good prediction of π tlp . A more negative π tlp (higher leaf drought tolerance) was coordinated with higher LDMC and higher iWUE. This pattern was consistent among PFTs and also after accounting for phylogenetic relatedness. However, the coordination of π tlp with other traits was weak. For LT and height, it was driven by the differences between PFTs. For SLA and LA, it was only observed after accounting for phylogenetic relatedness. The most parsimonious model predicting π tlp as a function of other traits retained LDMC and LA (adj. R 2 = 0.37). Since π tlp showed a strong phylogenetic signal, accounting for the influence of phylogenetic relatedness further improved π tlp prediction by 17%. In herbaceous temperate plants, there is relatively weak coordination between leaf drought tolerance ( π tlp ) and traits representing key dimensions of the LES and the global spectrum of plant form and function. None of the proxy traits considered here, alone or in combination, provided a strong prediction of π tlp across a large number of grassland plant species. Therefore, our work emphasizes the need for direct measurements of leaf hydraulics when estimating plant drought responses to better understand and predict species responses to environmental change. A free Plain Language Summary can be found within the Supporting Information of this article.
Consensus recommendations from the EXPeRT/PARTNER groups for the diagnosis and therapy of sex cord stromal tumors in children and adolescents
2021-03-24

Abstract As part of the European Union‐funded project designated Paediatric Rare Tumours Network ‐ European Registry (PARTNER), the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized nonmetastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin‐based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes, for example, DICER‐1 , so that specific follow‐up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.
Quantitative In Vitro-to-In Vivo Extrapolation: Nominal versus Freely Dissolved Concentration
2021-03-24

Discussions are ongoing on which dose metric should be used for quantitative <i>in vitro</i>-to-<i>in vivo</i> extrapolation (QIVIVE) of <i>in vitro</i> bioassay data. The nominal concentration of the test chemicals is most commonly used and easily accessible, while the concentration freely dissolved in the assay medium is considered to better reflect the bioavailable concentration but is tedious to measure. The aim of this study was to elucidate how much QIVIVE results will differ when using either nominal or freely dissolved concentrations. QIVIVE<sub>nom</sub> and QIVIVE<sub>free</sub> ratios, that is, the ratios of plasma concentrations divided by <i>in vitro</i> effect concentrations, were calculated for 10 pharmaceuticals using previously published nominal and freely dissolved effect concentrations for the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) and the activation of oxidative stress response. The QIVIVE<sub>nom</sub> ratios were higher than QIVIVE<sub>free</sub> ratios by up to a factor of 60. The risk of <i>in vivo</i> effects was classified as being high or low for four chemicals using the QIVIVE<sub>nom</sub> and for three chemicals using QIVIVE<sub>free</sub> ratios. Unambiguous classification was possible for nine chemicals by combining the QIVIVE<sub>nom</sub> or QIVIVE<sub>free</sub> ratios with the respective specificity ratios (SR<sub>nom</sub> or SR<sub>free</sub>) of the <i>in vitro</i> effect data, which helps to identify whether the specific effect was influenced by cytotoxicity. QIVIVE<sub>free</sub> models should be preferred as they account for differences in bioavailability between <i>in vitro</i> and <i>in vivo</i>, but QIVIVE<sub>nom</sub> may still be useful for screening the effects of large numbers of chemicals because it is generally more conservative. The use of SR of the <i>in vitro</i> effect data as a second classification factor is recommended for QIVIVE<sub>nom</sub> and QIVIVE<sub>free</sub> models because a clearer picture can be obtained with respect to the likelihood that a biological effect will occur and that it is not caused by nonspecific cytotoxicity.
Replication of a Novel Parkinson's Locus in a European Ancestry Population
2021-03-24

ABSTRACT Background A recently published East Asian genome‐wide association study of Parkinson;s disease (PD) reported 2 novel risk loci, SV2C and WBSCR17 . Objectives The objective of this study were to determine whether recently reported novel SV2C and WBSCR17 loci contribute to the risk of developing PD in European and East Asian ancestry populations. Methods We report an association analysis of recently reported variants with PD in the COURAGE‐PD cohort (9673 PD patients; 8465 controls) comprising individuals of European and East Asian ancestries. In addition, publicly available summary data (41,386 PD patients; 476,428 controls) were pooled. Results Our findings confirmed the role of the SV2C variant in PD pathogenesis (rs246814, COURAGE‐PD P European = 6.64 × 10 −4 , pooled PD P = 1.15 × 10 −11 ). The WBSCR17 rs9638616 was observed as a significant risk marker in the East Asian pooled population only ( P = 1.16 × 10 −8 ). Conclusions Our comprehensive study provides an up‐to‐date summary of recently detected novel loci in different PD populations and confirmed the role of SV2C locus as a novel risk factor for PD irrespective of the population or ethnic group analyzed. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
3D computational anatomy of the scaphoid and its waist for use in fracture treatment
2021-03-24

Abstract Background A detailed understanding of scaphoid anatomy helps anatomic fracture reduction, and optimal screw position. Therefore, we analysed (1) the size and shape variations of the cartilage and osseous surface, (2) the distribution of volumetric bone mineral density (vBMD) and (3) if the vBMD values differ between a peripheral and a central screw pathway? Methods Forty-three fresh frozen hand specimens (17 females, 26 males) were analysed with high-resolution peripheral quantitative computed tomography (HR-pQCT) and dissected to compute a 3D-statistical osseous and cartilage surface model and a 3D-averaged vBMD model of the scaphoid. 3D patterns were analysed using principal component analysis (PCA). vBMD was analysed via averaging HR-pQCT grey values and virtual bone probing along a central and peripheral pathway. Results (1) PCA displayed most notable variation in length ranging from 1.7 cm (− 2SD) to 2.6 cm (mean) and 3.7 cm (+ 2SD) associated with differences of the width and configuration of the dorsal surface (curved and narrow (4 mm) to a wider width (9 mm)). (2) High vBMD was located in the peripheral zone. Lowest vBMD was observed in the centre and waist. (3) Virtual probing along a peripheral pathway near to the cartilage surfaces for the capitate and lunate allowed the center region to be bypassed, resulting in increased vBMD compared to a central pathway. Conclusion High anatomical variations regarding the osseous and cartilage surfaces were associated with three distinct concentrically arranged zones with notable different vBMD. The complex scaphoid anatomy with its waist might alter the strategy of fracture fixation, education and research.
Predicting adult Attention Deficit Hyperactivity Disorder (ADHD) using vocal acoustic features
2021-03-24

Abstract Background It is a key concern in psychiatric research to investigate objective measures to support and ultimately improve diagnostic processes. Current gold standard diagnostic procedures for attention deficit hyperactivity disorder (ADHD) are mainly subjective and prone to bias. Objective measures such as neuropsychological measures and EEG markers show limited specificity. Recent studies point to alterations of voice and speech production to reflect psychiatric symptoms also related to ADHD. However, studies investigating voice in large clinical samples allowing for individual-level prediction of ADHD are lacking. The aim of this study was to explore a role of prosodic voice measures as objective marker of ADHD. Methods 1005 recordings were analyzed from 387 ADHD patients, 204 healthy controls, and 100 clinical (psychiatric) controls. All participants (age range 18-59 years, mean age 34.4) underwent an extensive diagnostic examination according to gold standard methods and provided speech samples (3 min in total) including free and given speech. Paralinguistic features were calculated, and random forest based classifications were performed using a 10-fold cross-validation with 100 repetitions controlling for age, sex, and education. Association of voice features and ADHD-symptom severity assessed in the clinical interview were analyzed using random forest regressions. Results and Conclusion ADHD was predicted with AUC = 0.76. The analysis of a non-comorbid sample of ADHD resulted in similar classification performance. Paralinguistic features were associated with ADHD-symptom severity as indicated by random forest regression. In female participants, particularly with age &lt; 32 years, paralinguistic features showed the highest classification performance (AUC = 0.86). Paralinguistic features based on derivatives of loudness and fundamental frequency seem to be promising candidates for further research into vocal acoustic biomarkers of ADHD. Given the relatively good performance in female participants independent of comorbidity, vocal measures may evolve as a clinically supportive option in the complex diagnostic process in this patient group.