julilili42/papers huggingface dataset:
Testing the utility of dental morphological trait combinations for inferring human neutral genetic variation
2020-05-06

Researchers commonly rely on human dental morphological features in order to reconstruct genetic affinities among past individuals and populations, particularly since teeth are often the best preserved part of a human skeleton. Tooth form is considered to be highly heritable and selectively neutral and, therefore, to be an excellent proxy for DNA when none is available. However, until today, it remains poorly understood whether certain dental traits or trait combinations preserve neutral genomic signatures to a greater degree than others. Here, we address this long-standing research gap by systematically testing the utility of 27 common dental traits and &gt;134 million possible trait combinations in reflecting neutral genomic variation in a worldwide sample of modern human populations. Our analyses reveal that not all traits are equally well-suited for reconstructing population affinities. Whereas some traits largely reflect neutral variation and therefore evolved primarily as a result of genetic drift, others can be linked to nonstochastic processes such as natural selection or hominin admixture. We also demonstrate that reconstructions of population affinity based on many traits are not necessarily more reliable than those based on only a few traits. Importantly, we find a set of highly diagnostic trait combinations that preserve neutral genetic signals best (up to <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"><mml:mrow><mml:mover accent="true"><mml:mi>x</mml:mi><mml:mo>∼</mml:mo></mml:mover></mml:mrow></mml:math> r = 0.580; 95% r range = 0.293 to 0.758; P = 0.001). We propose that these trait combinations should be prioritized in future research, as they allow for more accurate inferences about past human population dynamics when using dental morphology as a proxy for DNA.
The large-sized darter Anhinga pannonica (Aves, Anhingidae) from the late Miocene hominid Hammerschmiede locality in Southern Germany
2020-05-06

We report fossils of the darter Anhinga pannonica Lambrecht, 1916 from two late Miocene (Tortonian, 11.62 and 11.44 Ma) avifaunas in Southern Germany. The material from the hominid locality Hammerschmiede near Pforzen represents the most comprehensive record of this species and includes most major postcranial elements except for the tarsometatarsus. We furthermore show that the putative cormorant Phalacrocorax brunhuberi (von Ammon, 1918) from the middle Miocene of Regensburg-Dechbetten is another, previously misclassified, record of A. pannonica, and this may also be true for early Miocene fossils described as P. intermedius Milne-Edwards, 1867. A. pannonica was distinctly larger than extant darters and reached the size of A. grandis from the late Miocene of North America. We detail that only fossils from the Miocene of Europe and Africa can be referred to A. pannonica, whereas putative records from Asia fall within the size range of extant darters. A. pannonica appears to have been a long-living species (16 to 6 Ma) with an extensive distribution from the equator to the northern mid-latitudes. The extinction of large-sized darters in Europe is likely to have been due to climatic cooling in the late Neogene, but the reasons for their disappearance in Africa and South America remain elusive.
A MinHash approach for fast scanpath classification
2020-05-06

The visual scanpath describes the shift of visual attention over time. Characteristic patterns in the attention shifts allow inferences about cognitive processes, performed tasks, intention, or expertise. To analyse such patterns, the scanpath is often represented as a sequence of symbols that can be used to calculate a similarity score to other scanpaths. However, as the length of the scanpath or the number of possible symbols increases, established methods for scanpath similarity become inefficient, both in terms of runtime and memory consumption. We present a MinHash approach for efficient scanpath similarity calculation. Our approach shows competitive results in clustering and classification of scanpaths compared to established methods such as Needleman-Wunsch, but at a fraction of the required runtime. Furthermore, with time complexity of and constant memory consumption, our approach is ideally suited for real-time operation or analyzing large amounts of data.
Simultaneous spike-time locking to multiple frequencies
2020-05-06

Locking of neuronal spikes to external and internal signals is a ubiquitous neurophysiological mechanism that has been extensively studied in several brain areas and species. Using experimental data from the electrosensory system and concise mathematical models, we analyze how a single neuron can simultaneously lock to multiple frequencies. Our findings demonstrate how temporal and rate codes can complement each other and lead to rich neuronal representations of sensory signals.
Life‐threatening pneumonitis after first‐line treatment with osimertinib for primary T790M mutated non‐small cell lung cancer
2020-05-06

Epithelial growth factor receptor (EGFR) directed tyrosine kinase inhibitor (TKI) treatment is the standard approach in patients with advanced, EGFR ‐mutated non‐small cell lung cancer (NSCLC). Although benefit/risk ratio is favorable for these TKI and side effects are manageable in the vast majority of patients, severe and even life‐threatening side effects have been reported. TKI‐induced interstitial lung disease (ILD) has been reported for single cases in modest severity, predominantly in EGFR‐TKI pretreated patients. Here, we report a case of successful stabilization of a life‐threatening ILD in a de novo T790M mutated NSCLC during first‐line treatment with osimertinib. As osimertinib will be used more often in many EGFR‐positive NSCLC patients in the future, this potentially life‐threatening side effect should receive special attention, especially in first‐line treatment.
Interspinifex Ni sulfide ore from Victor South-McLeay, Kambalda, Western Australia
2020-05-06

Abstract Spinifex-textured olivine plates hosted in sulfides are usually named “interspinifex ore” in komatiite-hosted sulfide deposits. This ore type is rare but provides important genetic information on sulfide deposits, komatiite volcanology and thermomechanical erosion processes. Occurrences in Victor South-McLeay and Moran South (Kambalda, Western Australia) differ significantly from previously reported occurrences in their stratigraphic location, position within the ore profile and textural appearance. Thus, their formation process has to be reconsidered. Interspinifex ore reported here is situated in the lower portion of the basal lava flow between massive and net-textured sulfides in the centre of the embayment and between massive sulfides and older basalt in a “pinchout” where the sulfides melted sideways into older basalt on the embayment edge. Interspinifex ore is composed of up to 10-cm-long aggregates of parallel plates in the upper portion of massive sulfides and is overlain by barren komatiite. The texture does not allow for a classic single explanation. Thus, two possible formation mechanisms are envisaged: (1) A younger komatiite melt intrudes into its own olivine and sulfide liquid cumulate pile, while the sulfides are still liquid. The injection on top of the sulfides causes the formation of an emulsion, from which the spinifex forms due to the temperature gradient between the melts. (2) Interspinifex ore is a relic of an early komatiite flow formed in a series of successive pulses of komatiite and sulfide liquid. The spinifex of the komatiite is invaded by a younger batch of sulfide liquid replacing interstitial silicate melt.
Competencies for a healthy physically active lifestyle: Second-order analysis and multidimensional scaling
2020-05-06

<title>Abstract</title> The model of physical activity-related health competence (PAHCO) assumes that individuals require movement competence, control competence, and self-regulation competence to lead a healthy, physically active lifestyle. Although previous research has already established some measurement factors (n = 8) of the three dimensions, no attempts have so far been made to statistically aggregate them on the sub-competence level. Therefore, the goal of the present study was to test two additional factors for PAHCO and subsequently model the second-order structure with two samples from the fields of rehabilitation and prevention. We conducted two questionnaire surveys with persons with multiple sclerosis (n = 475) and teaching students undergoing a basic qualification course in physical education (n = 502). After performing exploratory items analysis, we used second-order confirmatory factor analysis (CFA) and multidimensional scaling to investigate whether the scales could be bundled in accordance with the PAHCO model. The CFAs with ten factors (42 items) demonstrated a good model fit. In contrast, the second-order analysis with a simple loading structure on the three sub-competencies revealed an unacceptable model fit. Instead, a second-order model variant was preferred (CFI = 0.926, RMSEA = 0.048, SRMR = 0.065) in which body awareness and self-efficacy had theory-conform cross-loadings. The results of multidimensional scaling (two-dimensional solution) were in line with the extracted second-order structure. The present results suggested that the extension of the measurement instrument to ten first-order factors was psychometrically justified. The results from the second-order analyses provided the basis for the creation of sum scores, representing manifest indicators of movement competence, control competence, and self-regulation competence. Future studies are needed that relate the sub-competencies of PAHCO to indicators of health-enhancing physical activity in relevant target Groups.
The immune response to influenza in older humans: beyond immune senescence
2020-05-07

Abstract Despite widespread influenza vaccination programs, influenza remains a major cause of morbidity and mortality in older adults. Age-related changes in multiple aspects of the adaptive immune response to influenza have been well-documented including a decline in antibody responses to influenza vaccination and changes in the cell-mediated response associated with immune senescence. This review will focus on T cell responses to influenza and influenza vaccination in older adults, and how increasing frailty or coexistence of multiple (≥2) chronic conditions contributes to the loss of vaccine effectiveness for the prevention of hospitalization. Further, dysregulation of the production of pro- and anti-inflammatory mediators contributes to a decline in the generation of an effective CD8 T cell response needed to clear influenza virus from the lungs. Current influenza vaccines provide only a weak stimulus to this arm of the adaptive immune response and rely on re-stimulation of CD8 T cell memory related to prior exposure to influenza virus. Efforts to improve vaccine effectiveness in older adults will be fruitless until CD8 responses take center stage.
Increasing success in college: Examining the impact of a project‐based introductory engineering course
2020-05-07

Abstract Background Project‐based learning has shown promise in improving learning outcomes for diverse students. However, studies on its impacts have largely focused on the perceptions of students and instructors or students' immediate performance. This study reports the impact of taking a project‐based introductory engineering course on students' subsequent academic success. Purpose/Hypothesis This quantitative study examines characteristics related to enrollment in the project‐based introductory engineering course and subsequent academic performance. We hypothesized that participation in the course would be associated with higher academic performance in subsequent engineering courses. In addition, we examined heterogeneity effects for students traditionally underrepresented in engineering education. Design/Method This study utilized data on students' demographics, academic preparation, course enrollment, and course performance from 1,318 engineering students from a large public university in Southern California. Logistic regression analysis with robust standard errors examined enrollment patterns. We applied propensity scores as inverse‐probability weights in multiple linear models to calculate the average treatment effect on the treated for participants from the project‐based introductory engineering course in five subsequent engineering courses. This analysis was conducted for all students and for selected student subgroups. Results Enrollment in the project‐based introductory engineering course was positively associated with students' performance in some subsequent engineering courses and did not adversely affect students traditionally underrepresented in engineering. Conclusions This study provides an example of a project‐based introductory engineering course that can support students' academic success in engineering. The benefits detected for some student populations (e.g., female) are encouraging for broadening engineering pathways.
Understanding Negation
2020-05-07

Abstract This chapter gives an overview of experimental studies concerned with the processing of explicit and implicit negation during language comprehension. The studies reported employ a large variety of experimental methods and paradigms, ranging from reaction or reading time experiments, to experiments measuring eye-tracking, EEG, or fMRI during reading. The chapter begins with an overview of early studies on negation processing and is structured according to the five main issues in the literature on negation processing: Is suppression routinely involved in negation processing? Does negation processing per default involve one or two meaning representations? Is negation integration delayed during the processing of negative sentences, and what role do pragmatic aspects play in this respect? How do embodied accounts of meaning representation deal with negation? Does negation processing involve general cognitive mechanisms that are also utilized during non-linguistic conflict processing?
Quantifying antibiotic impact on within-patient dynamics of extended-spectrum beta-lactamase resistance
2020-05-07

Antibiotic-induced perturbation of the human gut flora is expected to play an important role in mediating the relationship between antibiotic use and the population prevalence of antibiotic resistance in bacteria, but little is known about how antibiotics affect within-host resistance dynamics. Here we develop a data-driven model of the within-host dynamics of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. We use blaCTX-M (the most widespread ESBL gene family) and 16S rRNA (a proxy for bacterial load) abundance data from 833 rectal swabs from 133 ESBL-positive patients followed up in a prospective cohort study in three European hospitals. We find that cefuroxime and ceftriaxone are associated with increased blaCTX-M abundance during treatment (21% and 10% daily increase, respectively), while treatment with meropenem, piperacillin-tazobactam, and oral ciprofloxacin is associated with decreased blaCTX-M (8% daily decrease for all). The model predicts that typical antibiotic exposures can have substantial long-term effects on blaCTX-M carriage duration.
Whole-slide image analysis of the tumor microenvironment identifies low B-cell content as a predictor of adverse outcome in patients with advanced-stage classical Hodgkin lymphoma treated with BEACOPP
2020-05-07

A subset of patients with advanced-stage classical Hodgkin Lymphoma (cHL) relapse or progress following standard treatment. Given their dismal prognosis, identifying this group of patients upfront represents an important medical need. While prior research has identified characteristics of the tumor microenvironment, which are associated with cHL outcomes, biomarkers that are developed and validated in this high-risk group are still missing. Here, we applied whole-slide image analysis (WSI), a quantitative, large-scale assessment of tumor composition that utilizes conventional histopathology slides. We conducted WSI on a study cohort with pre-treatment biopsies of 340 advanced-stage cHL patients enrolled in the HD12 and HD15 trials of the German Hodgkin Study Group (GHSG), and tested our results in in a validation cohort of 147 advanced-stage cHL patients within the GHSG HD18 trial. All patients were treated with BEACOPP-based regimens. By quantifying T cells, B cells, Hodgkin-Reed-Sternberg-cells and macrophages with WSI, 80% of all cells in the tumor tissue were identified. Crucially, low B cell count was associated with significantly reduced progression-free survival (PFS) and overall survival (OS), while T cell-, macrophage- and Hodgkin-Reed-Sternberg-cell content was not associated with the risk of progression or relapse in the study cohort. We further validated low B cell content as a prognostic factor of PFS and OS in the validation cohort and demonstrate good inter-observer agreement of WSI. WSI may represent a key tool for risk stratification of advanced-stage cHL that can easily be added to the standard diagnostic histopathology work-up.
Cortical Thickness Trajectories across the Lifespan: Data from 17,075 healthy individuals aged 3-90 years
2020-05-07

Abstract Delineating age-related cortical trajectories in healthy individuals is critical given the association of cortical thickness with cognition and behaviour. Previous research has shown that deriving robust estimates of age-related brain morphometric changes requires large-scale studies. In response, we conducted a large-scale analysis of cortical thickness in 17,075 individuals aged 3-90 years by pooling data through the Lifespan Working group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium. We used fractional polynomial (FP) regression to characterize age-related trajectories in cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma (LMS) method. Inter-individual variability was estimated using meta-analysis and one-way analysis of variance. Overall, cortical thickness peaked in childhood and had a steep decrease during the first 2-3 decades of life; thereafter, it showed a gradual monotonic decrease which was steeper in men than in women particularly in middle-life. Notable exceptions to this general pattern were entorhinal, temporopolar and anterior cingulate cortices. Inter-individual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results reconcile uncertainties about age-related trajectories of cortical thickness; the centile values provide estimates of normative variance in cortical thickness, and may assist in detecting abnormal deviations in cortical thickness, and associated behavioural, cognitive and clinical outcomes.
The Role of Reconstructive Surgery and Brachytherapy in Pediatric Bladder/Prostate Rhabdomyosarcoma
2020-05-07

Combining brachytherapy with surgery results in a high bladder preservation rate and improves event-free survival compared to surgery alone in children with bladder/prostate rhabdomyosarcoma. The combination is also effective in treating local tumor relapse, and is associated with less extensive reconstructive procedures due to exclusion of tumors of unfavorable size and location for brachytherapy.
Subcortical Volume Trajectories across the Lifespan: Data from 18,605 healthy individuals aged 3-90 years
2020-05-07

Abstract Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalised on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine the age-related morphometric trajectories of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum early in life; the volume of the basal ganglia showed a gradual monotonic decline thereafter while the volumes of the thalamus, amygdala and the hippocampus remained largely stable (with some degree of decline in thalamus) until the sixth decade of life followed by a steep decline thereafter. The lateral ventricles showed a trajectory of continuous enlargement throughout the lifespan. Significant age-related increase in inter-individual variability was found for the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to derive risk predictions for the early identification of diverse clinical phenotypes.
A case report of fatal disseminated fungal sepsis in a patient with ARDS and extracorporeal membrane oxygenation
2020-05-07

Abstract Background With the following report we want to present an unusual case of a patient suffering from acute respiratory distress syndrome with early discovery of bacterial pathogens in bronchoalveolar liquid samples that developed a fatal undiscovered disseminated fungal infection. Case presentation A 67-year-old man was admitted to our university hospital with dyspnea. Progressive respiratory failure developed leading to admission to the intensive care unit, intubation and prone positioning was necessary. To ensure adequate oxygenation and lung protective ventilation veno-venous extracorporeal membrane oxygenation was established. Despite maximal therapy and adequate antiinfective therapy of all discovered pathogens the condition of the patient declined further and he deceased. Postmortem autopsy revealed Mucor and Aspergillus mycelium in multiple organs such as lung, heart and pancreas as the underlying cause of his deterioration and death. Conclusion Routine screening re-evaluation of every infection is essential for adequate initiation and discontinuation of every antiinfective therapy. In cases with unexplained deterioration and unsuccessful sampling the possibility for diagnostic biopsies should be considered.
In situ detection of protein interactions for recombinant therapeutic enzymes
2020-05-07

Abstract Despite their therapeutic potential, many protein drugs remain inaccessible to patients since they are difficult to secrete. Each recombinant protein has unique physicochemical properties and requires different machinery for proper folding, assembly, and post-translational modifications (PTMs). Here we aimed to identify the machinery supporting recombinant protein secretion by measuring the protein-protein interaction (PPI) networks of four different recombinant proteins (SERPINA1, SERPINC1, SERPING1 and SeAP) with various PTMs and structural motifs using the proximity-dependent biotin identification (BioID) method. We identified PPIs associated with specific features of the secreted proteins using a Bayesian statistical model, and found proteins involved in protein folding, disulfide bond formation and N-glycosylation were positively correlated with the corresponding features of the four model proteins. Among others, oxidative folding enzymes showed the strongest association with disulfide bond formation, supporting their critical roles in proper folding and maintaining the ER stability. Knockdown of disulfide-isomerase PDIA4, a measured interactor with significance for SERPINC1 but not SERPINA1, led to the decreased secretion of SERPINC1, which relies on its extensive disulfide bonds, compared to SERPINA1, which has no disulfide bonds. Proximity-dependent labeling successfully identified the transient interactions supporting synthesis of secreted recombinant proteins and refined our understanding of key molecular mechanisms of the secretory pathway during recombinant protein production.