julilili42/papers huggingface dataset:
Scaling Up Intervention Studies to Investigate Real-Life Foreign Language Learning in School
2019-03-01

Abstract Intervention studies typically target a focused aspect of language learning that is studied over a relatively short time frame for a relatively small number of participants in a controlled setting. While for many research questions, this is effective, it can also limit the ecological validity and relevance of the results for real-life language learning. In educational science, large-scale randomized controlled field trials (RCTs) are seen as the gold standard method for addressing this challenge—yet they require intervention to scale to hundreds of learners in their varied, authentic contexts. We discuss the use of technology in support of large-scale interventions that are fully integrated in regular classes in secondary school. As an experimentation platform, we developed a web-based workbook to replace a printed workbook widely used in German schools. The web-based FeedBook provides immediate scaffolded feedback to students on form and meaning for various exercise types, covering the full range of constructions in the seventh-grade English curriculum. Following the conceptual discussion, we report on the first results of an ongoing, yearlong RCT. The results confirm the effectiveness of the scaffolded feedback, and the approach makes students and learning process variables accessible for the analysis of learning in a real-world context.
Disentangling bottom-up versus top-down and low-level versus high-level influences on eye movements over time
2019-03-01

Bottom-up and top-down as well as low-level and high-level factors influence where we fixate when viewing natural scenes. However, the importance of each of these factors and how they interact remains a matter of debate. Here, we disentangle these factors by analyzing their influence over time. For this purpose, we develop a saliency model that is based on the internal representation of a recent early spatial vision model to measure the low-level, bottom-up factor. To measure the influence of high-level, bottom-up features, we use a recent deep neural network-based saliency model. To account for top-down influences, we evaluate the models on two large data sets with different tasks: first, a memorization task and, second, a search task. Our results lend support to a separation of visual scene exploration into three phases: the first saccade, an initial guided exploration characterized by a gradual broadening of the fixation density, and a steady state that is reached after roughly 10 fixations. Saccade-target selection during the initial exploration and in the steady state is related to similar areas of interest, which are better predicted when including high-level features. In the search data set, fixation locations are determined predominantly by top-down processes. In contrast, the first fixation follows a different fixation density and contains a strong central fixation bias. Nonetheless, first fixations are guided strongly by image properties, and as early as 200 ms after image onset, fixations are better predicted by high-level information. We conclude that any low-level, bottom-up factors are mainly limited to the generation of the first saccade. All saccades are better explained when high-level features are considered, and later, this high-level, bottom-up control can be overruled by top-down influences.
<p>Clinical utility of tafenoquine in the prevention of relapse of <em>Plasmodium vivax</em> malaria: a review on the mode of action and emerging trial data</p>
2019-03-01

Tafenoquine is an 8-aminoquinoline with activity against all human life cycle stages of <i>Plasmodium vivax</i>, including dormant liver stages - so called hypnozoites. Its long half-life of ~15 days is allowing for a single exposure regimen. It has been under development since 1980 and received approval by the US Food and Drug Administration in summer 2018 as an anti-relapse drug for <i>P. vivax</i> malaria in patients aged 16 years and older and for prophylaxis of malaria caused by any <i>Plasmodium</i> species in adults. Prior to tafenoquine administration, glucose-6-phosphate dehydrogenase (G6PD) deficiency needs to be excluded by testing. Individuals with a deficient G6PD activity are at risk of tafenoquine-induced hemolysis - as is the case for primaquine, the mainstay drug for <i>P. vivax</i> radical cure. A wealth of clinical studies have been conducted and are still ongoing to assess the safety, tolerability, and efficacy of tafenoquine. This review focuses on data emerging from the latest clinical trials on <i>P. vivax</i> radical cure with tafenoquine, the key studies for regulatory approval of tafenoquine, and elucidates the latest hypothesis on the mode of action.
Resistance to anoikis in transcoelomic shedding: the role of glycolytic enzymes
2019-03-01

Abstract Detachment of cells from the extracellular matrix into the peritoneal cavity initiates a cascade of metabolic alterations, leading usually to cell death by apoptosis, so-called anoikis . Glycolytic enzymes enable the switch from oxidative phosphorylation to aerobic glycolysis and allow resistance to anoikis of shed tumour cells. These enzymes also have moonlighting activities as protein kinases and transcription factors. Phosphoglycerate kinase (PGK) and pyruvate kinase are the only glycolytic enzymes generating ATP in the hexokinase pathway. Hypoxia, EGFR activation, expression of K-Ras G12V and B-Raf V600E induce mitochondrial translocation of phosphoglycerate kinase 1 (PGK1). Mitochondrial PGK1 acts as a protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1), reducing mitochondrial pyruvate utilization, suppressing reactive oxygen species production, increasing lactate production and promoting tumourigenesis. PGK1 also plays a role as a transcription factor once transported into the nucleus. Resistance to anoikis is also facilitated by metabolic support provided by cancer-associated fibroblasts (CAFs). Our series of experiments in-vitro and in the animal model showed that PGK1 knock-out or inhibition is effective in controlling development and growth of peritoneal metastasis (PM) of gastric origin, establishing a causal role of PGK1 in this development. PGK1 also increases CXCR4 and CXCL12 expression, which is associated with a metastatic phenotype and plays a role in the metastatic homing of malignant cells. Thus, PGK1, its modulators and target genes may be exploited as therapeutic targets for preventing development of PM and for enhancing cytotoxic effects of conventional systemic chemotherapy.
High naevus count and MC 1R red hair alleles contribute synergistically to increased melanoma risk
2019-03-01

Patients who live in areas of high ultraviolet radiation, and have many large naevi and the red hair colour phenotype, particularly those with the MC1R R/R genotype, have a high risk of melanoma above the threshold recommended for screening in other cancers. Therefore, they should undergo intensive physician-led surveillance. What's already known about this topic? A high number of acquired melanocytic naevi, the red hair phenotype and MC1R R alleles all independently increase melanoma risk. Women with atypical naevi have an increasing melanoma risk gradient from darker hair to lighter hair. Women with many naevi have an increasing melanoma risk gradient from those with no elements of the red hair phenotype, to those with freckles but not red hair, to those with red hair. What does this study add? In Queensland, Australia, people with ≥ 20 naevi (≥ 5 mm diameter) and MC1R R/R genotype have a 25-fold increased melanoma risk, relative to people with zero to four naevi and the MC1R WT/WT genotype. In Queensland, individuals with ≥ 20 naevi and the MC1R R/R genotype have an absolute melanoma risk to age 75 years of 23·3% for men and 19·3% for women. This effect is independent of CDKN2A genotype. Further research is required to determine the effect of areas of lower ultraviolet radiation, as this study took place in the Queensland, Australia, which is an area of high ultraviolet radiation. MC1R R/r genotype is associated with increased total body naevus count but this is not the case for R/R. What is the translational message? Patients with many large naevi and the red hair colour phenotype, particularly those with an MC1R R/R genotype, have an unusually high risk of melanoma. In a high ultraviolet environment, this risk exceeds the threshold recommended for screening in other cancers, and such individuals should undergo intensive, regular, physician-led surveillance. Patients with many large naevi but with non-red colour hair may benefit further from clinical MC1R genotyping.
Phase III study of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): The ARCHES trial.
2019-03-01

687 Background: ENZA, a potent androgen receptor inhibitor, has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Efficacy of ENZA with ADT in men with mHSPC is unknown. Methods: ARCHES is a multinational, double-blind, phase 3 study (NCT02677896). Patients (pts) with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel therapy. Primary endpoint was radiographic progression-free survival (rPFS) assessed centrally or death within 24 weeks of treatment discontinuation. Secondary endpoints included time to prostate-specific antigen (PSA) progression, PSA and radiographic responses and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n=574) or PBO (n=576); baseline characteristics were balanced between groups. Overall, 67% had distant metastasis at initial diagnosis; 63% had high volume disease, 18% had prior docetaxel. Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); similar significant improvements in rPFS were reported in prespecified subgroups of disease volume, pattern of spread, region and prior docetaxel (HRs 0.24–0.53). Secondary endpoints improved with ENZA + ADT (Table); OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs PBO + ADT in men with mHSPC, with a preliminary safety analysis that appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Acknowledgements: Medical writing and editing assistance was provided by Stephanie Rippon, MBio, and Lauren Smith from Complete HealthVizion, funded by the study sponsors. This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Clinical trial information: NCT02677896. [Table: see text]
Person Independent, Privacy Preserving, and Real Time Assessment of Cognitive Load using Eye Tracking in a Virtual Reality Setup
2019-03-01

Eye tracking is handled as key enabling technology to VR and AR for multiple reasons, since it not only can help to massively reduce computational costs through gaze-based optimization of graphics and rendering, but also offers a unique opportunity to design gaze-based personalized interfaces and applications. Additionally, the analysis of eye tracking data allows to assess the cognitive load, intentions and actions of the user. In this work, we propose a person-independent, privacy-preserving and gaze-based cognitive load recognition scheme for drivers under critical situations based on previously collected driving data from a driving experiment in VR including a safety critical situation. Based on carefully annotated ground-truth information, we used pupillary information and performance measures (inputs on accelerator, brake, and steering wheel) to train multiple classifiers with the aim of assessing the cognitive load of the driver. Our results show that incorporating eye tracking data into the VR setup allows to predict the cognitive load of the user at a high accuracy above 80%. Beyond the specific setup, the proposed framework can be used in any adaptive and intelligent VR/AR application.
The First NuSTAR Observation of 4U 1538–522: Updated Orbital Ephemeris and a Strengthened Case for an Evolving Cyclotron Line Energy
2019-03-01

Abstract We have performed a comprehensive spectral and timing analysis of the first NuSTAR observation of the high-mass X-ray binary 4U 1538−522. The observation covers the X-ray eclipse of the source, plus the eclipse ingress and egress. We use the new measurement of the mid-eclipse time to update the orbital parameters of the system and find marginally significant evolution in the orbital period, with . The cyclotron line energy is found to be approximately 1.2 keV higher than RXTE measurements from 1997 to 2003, in line with the increased energy observed by Suzaku in 2012 and strengthening the case for secular evolution of 4U 1538−522’s CRSF. We additionally characterize the behavior of the iron fluorescence and emission lines and line-of-sight absorption as the source moves into and out of eclipse.
Update Breast Cancer 2019 Part 2 – Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice
2019-03-01

Abstract The treatment of patients with advanced breast cancer has developed further in recent years. In addition to therapeutic progress in the established subgroups (hormone receptor and HER2 status), there are now therapies which are geared to individual molecular characteristics, such as PARP inhibitor therapy in BRCA-mutated patients. In addition to this, tests are being developed which are intended to establish additional markers within subgroups in order to predict the efficacy of a therapy. PI3K mutation testing in HER2-negative, hormone-receptor-positive tumours and PD-L1 testing of immune cells in triple-negative tumours are expected to become established in clinical practice in order to select patients for the respective therapies. With new therapeutic approaches, new adverse effects also appear. The management of these adverse effects, just as those of classical therapy (supportive therapy), is essential with the introduction of new treatments in order to preserve patientsʼ quality of life. Knowledge regarding measures to preserve and improve quality of life has significantly increased in recent years. Lifestyle factors should be taken into account, as should modern therapeutic methods. This review summarises the latest studies and publications and evaluates them in regard to the relevance for clinical practice.
Update Breast Cancer 2019 Part 1 – Implementation of Study Results of Novel Study Designs in Clinical Practice in Patients with Early Breast Cancer
2019-03-01

Abstract For many years, small but significant advancements have been made time and again in the prevention and treatment of early breast cancer. The so-called panel gene analyses are becoming more and more important in prevention, since the risk due to the tested genes is better understood and as a result, concepts for integration in health care can be developed. In the adjuvant situation, the first study in the so-called post-neoadjuvant situation was able to demonstrate a clear improvement in the prognosis with an absent pathological complete remission following trastuzumab or pertuzumab + trastuzumab. Additional studies with this post-neoadjuvant therapeutic concept are still being conducted at present. The CDK4/6 inhibitors which had shown a significant improvement in progression-free survival in a metastatic situation are currently being tested in the adjuvant situation in large therapeutic studies. These and other new data for the treatment or prevention of primary breast cancer are presented in this review against the backdrop of current studies.
Methionine Limitation Impairs Pathogen Expansion and Biofilm Formation Capacity
2019-03-01

New antibiotics that attack novel targets are needed to circumvent widespread resistance to conventional drugs. Bacterial anabolic pathways, such as the enzymes for biosynthesis of the essential amino acid methionine, have been proposed as potential targets. However, the eligibility of enzymes in these pathways as drug targets is unclear because metabolites might be acquired from the environment to overcome inhibition. We investigated the nutritional needs of methionine auxotrophs of the pathogens Staphylococcus aureus , Pseudomonas aeruginosa , and Escherichia coli . We found that each auxotrophic strain retained a growth disadvantage at methionine concentrations mimicking those available in vivo and showed that biofilm biomass was strongly influenced by endogenous methionine biosynthesis. Our experiments suggest that inhibition of the methionine biosynthesis pathway has deleterious effects even in the presence of external methionine. Therefore, additional efforts to validate the effects of methionine biosynthesis inhibitors in vivo are warranted.
Linguistic Information in Auditory Dynamic Events Contributes to the Detection of Fine, Not Coarse Event Boundaries
2019-03-01

Human observers (comprehenders) segment dynamic information into discrete events. That is, although there is continuous sensory information, comprehenders perceive boundaries between two meaningful units of information. In narrative comprehension, comprehenders use linguistic, non-linguistic , and physical cues for this event boundary perception. Yet, it is an open question - both from a theoretical and an empirical perspective - how linguistic and non-linguistic cues contribute to this process. The current study explores how linguistic cues contribute to the participants' ability to segment continuous auditory information into discrete, hierarchically structured events. Native speakers of German and non-native speakers, who neither spoke nor understood German, segmented a German audio drama into coarse and fine events. Whereas native participants could make use of linguistic, non-linguistic, and physical cues for segmentation, non-native participants could only use non-linguistic and physical cues. We analyzed segmentation behavior in terms of the ability to identify coarse and fine event boundaries and the resulting hierarchical structure. Non-native listeners identified almost identical coarse event boundaries as native listeners, but missed some of the fine event boundaries identified by the native listeners. Interestingly, hierarchical event perception (as measured by hierarchical alignment and enclosure) was comparable for native and non-native participants. In summary, linguistic cues contributed particularly to the identification of certain fine event boundaries. The results are discussed with regard to the current theories of event cognition.
Parton-shower effects in electroweak WZjj production at the next-to-leading order of QCD
2019-03-01

\\n We present an implementation of production via vector-boson fusion in the POWHEG BOX, a public tool for the matching of next-to-leading order QCD calculations with multi-purpose parton-shower generators. We provide phenomenological results for electroweak production with fully leptonic decays at the LHC in realistic setups and discuss theoretical uncertainties associated with the simulation. We find that beyond the leading-order approximation the dependence on the unphysical factorization and renormalization scales is mild. The two tagging jets are furthermore very stable against parton-shower effects. However, considerable sensitivities to the shower Monte-Carlo program used are observed for central-jet veto observables.\\n
Between-speaker variability and temporal organization of the first formant
2019-03-01

First formant (F1) trajectories of vocalic intervals were divided into positive and negative dynamics. Positive F1 dynamics were defined as the speeds of F1 increases to reach the maxima, and negative F1 dynamics as the speeds of F1 decreases away from the maxima. Mean, standard deviation, and sequential variability were measured for both dynamics. Results showed that measures of negative F1 dynamics explained more between-speaker variability, which was highly congruent with a previous study using intensity dynamics [He and Dellwo (2017). J. Acoust. Soc. Am. 141, EL488–EL494]. The results may be explained by speaker idiosyncratic articulation.
Staging laparoscopy and Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for peritoneal metastasis: safe access to the abdomen
2019-03-01

Abstract Background Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is an innovative drug delivery technique. Most common indication is palliative therapy of peritoneal metastasis of gastrointestinal and gynecological origin in the salvage situation. Access to the abdomen is the critical step of the procedure, since most patients had previous surgery. Potential pitfalls include non-access because of adhesions, bowel access lesions and postoperative subcutaneous toxic emphysema. Methods We propose a technique, the “finger-access technique” that might prevent largely these pitfalls. A minilaparotomy of 3 cm is performed in the midline, a finger introduced into the abdomen and a 5-mm double-balloon trocar (no Hasson trocar) is placed under finger protection at some distance of the first incision. The fascia of the minilaparotomy, not the skin, is then closed. The abdomen is insufflated with CO 2 and tightness is controlled with saline solution in the minilaparotomy. A second 10–12 mm trocar is then introduced under videoscopic control. The first trocar is then visualized through the second one to exclude a bowel lesion during first access. Results and conclusions In our hands, this access technique has shown to be safe and effective.
Derivation of the 1d nonlinear Schrödinger equation from the 3d quantum many-body dynamics of strongly confined bosons
2019-03-01

We consider the dynamics of N interacting bosons initially exhibiting Bose–Einstein condensation. Due to an external trapping potential, the bosons are strongly confined in two spatial directions, with the transverse extension of the trap being of order ε. The non-negative interaction potential is scaled such that its scattering length is positive and of order (N/ε2)−1 and the range of the interaction scales as (N/ε2)−β for β ∈ (0, 1). We prove that in the simultaneous limit N → ∞ and ε → 0, the condensation is preserved by the dynamics and the time evolution is asymptotically described by a cubic defocusing nonlinear Schrödinger equation in one dimension, where the strength of the nonlinearity depends on the interaction and on the confining potential. This is the first derivation of a lower-dimensional effective evolution equation for singular potentials scaling with β≥12 and lays the foundations for the derivation of the physically relevant one-dimensional Gross–Pitaevskii equation (β = 1). For our analysis, we adapt an approach by Pickl to the problem with strong confinement.
In Vivo Imaging of Tumor Senescence with a novel beta-Galactosidase specific PET Tracer
2019-03-01

Senescence, a durable cell cycle arrest, is a stress response influencing the treatment outcome in cancer. Currently senescence-associated ß-galactosidase is the gold standard biomarker for ex vivo senescence detection. Here we developed the PET tracer [18F] FPyGal for in vivo detection of senescent cells in cancer patients.