julilili42/papers huggingface dataset:
Multistage classification identifies altered cortical phase- and amplitude-coupling in Multiple Sclerosis
2021-02-18

Abstract Distinguishing groups of subjects or experimental conditions in a high-dimensional feature space is a common goal in modern neuroimaging studies. Successful classification depends on the selection of relevant features as not every neuronal signal component or parameter is informative about the research question at hand. Here, we developed a novel unsupervised multistage analysis approach that combines dimensionality reduction, bootstrap aggregating and multivariate classification to select relevant neuronal features. We tested the approach by identifying changes of brain-wide electrophysiological coupling in Multiple Sclerosis. Multiple Sclerosis is a demyelinating disease of the central nervous system that can result in cognitive decline and physical disability. However, related changes in large-scale brain interactions remain poorly understood and corresponding non-invasive biomarkers are sparse. We thus compared brain-wide phase- and amplitude-coupling of frequency specific neuronal activity in relapsing-remitting Multiple Sclerosis patients (n = 17) and healthy controls (n = 17) using magnetoencephalography. Our analysis approach allowed us to identify systematic and non-redundant changes of both phase- and amplitude-coupling in the diseased brain. Changes included both, increased and decreased neuronal coupling in wide-spread, bilateral neuronal networks across a broad range of frequencies. These changes allowed to successfully classify patients and controls with an accuracy of 84%. Furthermore, classification confidence predicted behavioral scores of disease severity. In sum, our results unravel systematic changes of large-scale phase- and amplitude coupling in Multiple Sclerosis. Furthermore, our results establish a new analysis approach to efficiently contrast high-dimensional neuroimaging data between experimental groups or conditions. Highlights A novel multistage approach to analyze high-dimensional neuronal coupling data. Application to MEG recordings in relapsing-remitting Multiple Sclerosis patients. Identification of altered phase- and amplitude-coupling in Multiple Sclerosis. Classification of patients and controls with 84% accuracy. Classification confidence predicts behavioral scores of disease severity.
Non-destructive extraction of DNA from preserved tissues in medical collections
2021-02-18

Abstract Museum and medically fixed material are valuable samples for the study of historical soft tissues and represent a pathogen-specific source for retrospective molecular investigations. However, current methods for the molecular analysis are inherently destructive, posing a dilemma between performing a study with the available technology thus damaging the sample - or conserving the material for future investigations. Here we present an unprecedented non-destructive alternative that facilitates the genetic analysis of fixed wet tissues while avoiding tissue damage. We extracted DNA from the fixed tissues as well as their embedding fixative solution, to quantify the DNA that was transferred to the liquid component. Our results prove that human ancient DNA can be retrieved from the fixative material of stored medical specimens and provide new options for the sampling of valuable curated collections. Method summary We compared the metagenomic content of historical tissues and their embedding liquid to retrieve DNA from the host and specified pathogens based on the diagnosis of the sample. We applied ancient DNA research techniques, including in-solution hybridization capture with DNA baits for human mitochondrial DNA, Mycobacterium tuberculosis, Mycobacterium leprae , and Treponema pallidum .
“An Animal That May Make Promises” (GM II, 1–3)
2021-02-18

The electrifying opening question in the second essay of Nietzsche’s On the Genealogy of Morals can be read as an aphorism as it is defined in the preface, namely, as something that requires creative deciphering. For it contains hooks and snares in which a merely superficial reading quickly becomes entangled. Furthermore, one would like to perceive its connection with the first treatise, with its oppositions of Good–Bad and Good–Evil, or between the master morality and slave morality.
Introduction
2021-02-18

Although very few copies of Friedrich Nietzsche’s published works were sold during the productive part of his life prior to his mental collapse in 1889 at the age of 44, in the last decade of the nineteenth century and the early decades of the twentieth century he quickly became the best-known and most influential German writer and thinker. This was especially, but not exclusively, so in German-speaking countries, where he gained fame primarily as a ferocious critic of Christianity, religion in general, traditional morality, and liberal democratic and socialist politics. He then quickly also became well known internationally as one of the first “avant-garde” philosophers – more, in his own words, an “artist, shaman and seducer” than a traditional philosopher. And he did not lack confidence.
Exploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity
2021-02-19

Abstract The humoral immune response to SARS-CoV-2 is a benchmark for immunity and detailed analysis is required to understand the manifestation and progression of COVID-19, monitor seroconversion within the general population, and support vaccine development. The majority of currently available commercial serological assays only quantify the SARS-CoV-2 antibody response against individual antigens, limiting our understanding of the immune response. To overcome this, we have developed a multiplex immunoassay (MultiCoV-Ab) including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses. Compared to three broadly used commercial in vitro diagnostic tests, our MultiCoV-Ab achieves a higher sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. We find a high response against endemic coronaviruses in our sample set, but no consistent cross-reactive IgG response patterns against SARS-CoV-2. Here we show a robust, high-content-enabled, antigen-saving multiplex assay suited to both monitoring vaccination studies and facilitating epidemiologic screenings for humoral immunity towards pandemic and endemic coronaviruses.
Auxin and gibberellin signaling cross-talk promotes hypocotyl xylem expansion and cambium homeostasis
2021-02-19

Abstract During secondary growth, the thickening of plant organs, wood (xylem) and bast (phloem) is continuously produced by the vascular cambium. In Arabidopsis hypocotyl and root, we can distinguish two phases of secondary growth based on cell morphology and production rate. The first phase, in which xylem and phloem are equally produced, precedes the xylem expansion phase in which xylem formation is enhanced and xylem fibers differentiate. It is known that gibberellins (GA) trigger this developmental transition via degradation of DELLA proteins and that the cambium master regulator BREVIPEDICELLUS/KNAT1 (BP/KNAT1) and receptor like kinases ERECTA and ERL1 regulate this process downstream of GA. However, our understanding of the regulatory network underlying GA-mediated secondary growth is still limited. Here, we demonstrate that DELLA-mediated xylem expansion in Arabidopsis hypocotyl is mainly achieved through DELLA family members RGA and GAI, which promote cambium senescence. We further show that AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8, which physically interact with DELLAs, specifically repress phloem proliferation and induce cambium senescence during the xylem expansion phase. Moreover, the inactivation of BP in arf6 arf8 background revealed an essential role for ARF6 and ARF8 in cambium establishment and maintenance. Overall, our results shed light on a pivotal hormone cross-talk between GA and auxin in the context of plant secondary growth.
Neural Code of Motor Planning and Execution during Goal-Directed Movements in Crows
2021-02-19

The planning and execution of head-beak movements are vital components of bird behavior. They require integration of sensory input and internal processes with goal-directed motor output. Despite its relevance, the neurophysiological mechanisms underlying action planning and execution outside of the song system are largely unknown. We recorded single-neuron activity from the associative endbrain area nidopallium caudolaterale (NCL) of two male carrion crows ( Corvus corone ) trained to plan and execute head-beak movements in a spatial delayed response task. The crows were instructed to plan an impending movement toward one of eight possible targets on the left or right side of a touchscreen. In a fraction of trials, the crows were prompted to plan a movement toward a self-chosen target. NCL neurons signaled the impending motion direction in instructed trials. Tuned neuronal activity during motor planning categorically represented the target side, but also specific target locations. As a marker of intentional movement preparation, neuronal activity reliably predicted both target side and specific target location when the crows were free to select a target. In addition, NCL neurons were tuned to specific target locations during movement execution. A subset of neurons was tuned during both planning and execution period; these neurons experienced a sharpening of spatial tuning with the transition from planning to execution. These results show that the avian NCL not only represents high-level sensory and cognitive task components, but also transforms behaviorally-relevant information into dynamic action plans and motor execution during the volitional perception-action cycle of birds. SIGNIFICANCE STATEMENT Corvid songbirds have become exciting new models for understanding complex cognitive behavior. As a key neural underpinning, the endbrain area nidopallium caudolaterale (NCL) represents sensory and memory-related task components. How such representations are converted into goal-directed motor output remained unknown. In crows, we report that NCL neurons are involved in the planning and execution of goal-directed movements. NCL neurons prospectively signaled motion directions in instructed trials, but also when the crows were free to choose a target. NCL neurons showed a target-specific sharpening of tuning with the transition from the planning to the execution period. Thus, the avian NCL not only represents high-level sensory and cognitive task components, but also transforms relevant information into action plans and motor execution.
Analyzing Phonetic Data with Generalized Additive Mixed Models
2021-02-19

This chapter provides a tutorial on how to analyze phonetic data with Generalized Additive Mixed Models (GAMs). It presents analyses for three example datasets, all of which address aspects of the phonetics of Taiwan Mandarin. The first dataset contains response time data from an auditory priming experiment. For the second dataset, the chapter focuses on the realizations of Mandarin high-level tones by different speaker groups in Taiwan. The third dataset addresses the ongoing merging of two sets of sibilants in Taiwan Mandarin. GAMs can model time-varying response variables. The linear mixed model can allow the intercept and slope of regression lines for individual subjects to vary, but it cannot handle the case in which functional relations are not linear but instead wiggly. In phonetics, a lot of features that speech clinician measure change over time. These include pitch, intensity and formants. Time is a numeric variable ranging from one to ten in normalized time.
Using Y-chromosome capture enrichment to resolve haplogroup H2 shows new evidence for a two-Path Neolithic expansion to Western Europe
2021-02-19

Abstract Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30 years to investigate the history of humans from a maternal and paternal perspective. Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture arrays such as the 1240K, ancient DNA studies often fail to utilize the unique perspective that the NRY can yield. Here we introduce a new DNA enrichment assay, coined YMCA (Y-mappable capture assay), that targets the “mappable” regions of the NRY. We show that compared to low-coverage shotgun sequencing and 1240K capture, YMCA significantly improves the coverage and number of sites hit on the NRY, increasing the number of Y-haplogroup informative SNPs, and allowing for the identification of previously undiscovered variants. To illustrate the power of YMCA, we show that the analysis of ancient Y-chromosome lineages can help to resolve Y-chromosomal haplogroups. As a case study, we focus on H2, a haplogroup associated with a critical event in European human history: the Neolithic transition. By disentangling the evolutionary history of this haplogroup, we further elucidate the two separate paths by which early farmers expanded from Anatolia and the Near East to western Europe.
Regarding an “Almost Anything Goes” Attitude Toward Methods in Psychology
2021-02-19

Our outline points out three aspects of a new&#13;\\npost-modern methodology in psychology: liberal, pluralistic, and&#13;\\nmore tolerant: liberal because it rejects rules that are too strict&#13;\\nin favor of more freedom in the choice of method, pluralistic&#13;\\nbecause it conveys an “almost anything goes” attitude toward&#13;\\nmethods, and more tolerant because mutual tolerance among&#13;\\nresearchers is vital for a pluralism of methods. Psychological&#13;\\nphenomena are complex and can best be understood by using&#13;\\ndifferent methods. However,&#13;\\nto get things working, tolerance must actively be lived. Of course,&#13;\\nmuch depends on our own willingness as researchers but also on&#13;\\nthe system’s arrangements. Psychology could be more colorful,&#13;\\nand we could all have more fun if we were to be more committed&#13;\\nto such a methodology.
Sonographic findings in coronavirus disease-19 associated liver damage
2021-02-19

Purpose This study was conducted to evaluate the role of liver sonography in patients with coronavirus disease 2019 (COVID-19) and elevated liver enzymes. Materials and methods In this retrospective study, patients tested positive for SARS-CoV-2 in our emergency ward between January 01 and April 24, 2020 and elevated liver enzymes were included (Cohort 1). Additionally, the local radiology information system was screened for sonographies in COVID-19 patients at the intensive care unit in the same period (Cohort 2). Liver sonographies and histologic specimen were reviewed and suspicious findings recorded. Medical records were reviewed for clinical data. Ultrasound findings and clinical data were correlated with severity of liver enzyme elevation. Results Cohort 1: 126 patients were evaluated, of which 47 (37.3%) had elevated liver enzymes. Severity of liver enzyme elevation was associated with death (p&lt;0.001). 8 patients (6.3%) had suspicious ultrasound findings, including signs of acute hepatitis (n = 5, e.g. thickening of gall bladder wall, hepatomegaly, decreased echogenicity of liver parenchyma) and vascular complications (n = 4). Cohort 2: 39 patients were evaluated, of which 14 are also included in Cohort 1. 19 patients (48.7%) had suspicious ultrasound findings, of which 13 patients had signs of acute hepatitis and 6 had vascular complications. Pathology was performed in 6 patients. Predominant findings were severe cholestasis and macrophage activation. Conclusion For most hospitalized COVID-19 patients, elevated liver enzymes cause little concern as they are only mild to moderate. However, in severely ill patients bedside sonography is a powerful tool to reveal different patterns of vascular, cholestatic or inflammatory complications in the liver, which are associated with high mortality. In addition, macrophage activation as histopathologic correlate for a hyperinflammatory syndrome seems to be a frequent complication in COVID-19.
Autosomal Dominant Gyrate Atrophy-Like Choroidal Dystrophy Revisited: 45 Years Follow-Up and Association with a Novel C1QTNF5 Missense Variant
2021-02-19

We present a long-term follow-up in autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD) and propose a possible genotype/phenotype correlation. Ophthalmic examination of six patients from two families revealed confluent areas of choroidal atrophy resembling gyrate atrophy, starting in the second decade of life. Progression continued centrally, reaching the fovea at about 60 years of age. Subretinal deposits, retinal pigmentation or choroidal neovascularization as seen in late-onset retinal degeneration (LORD) were not observed. Whole genome sequencing revealed a novel missense variant in the C1QTNF5 gene (p.(Q180E)) which was found in heterozygous state in all affected subjects. Haplotype analysis showed that this variant found in both families is identical by descent. Three-dimensional modeling of the possible supramolecular assemblies of C1QTNF5 revealed that the p.(Q180E) variant led to the destabilization of protein tertiary and quaternary structures, affecting both the stability of the single protomer and the entire globular head, thus exerting detrimental effects on the formation of C1QTNF5 trimeric globular domains and their interaction. In conclusion, we propose that the p.(Q180E) variant causes a specific phenotype, adGALCD, that differs in multiple clinical aspects from LORD. Disruption of optimal cell-adhesion mechanisms is expected when analyzing the effects of the point mutation at the protein level.
Efficient and flexible Integration of variant characteristics in rare variant association studies using integrated nested Laplace approximation
2021-02-19

Rare variants are thought to play an important role in the etiology of complex diseases and may explain a significant fraction of the missing heritability in genetic disease studies. Next-generation sequencing facilitates the association of rare variants in coding or regulatory regions with complex diseases in large cohorts at genome-wide scale. However, rare variant association studies (RVAS) still lack power when cohorts are small to medium-sized and if genetic variation explains a small fraction of phenotypic variance. Here we present a novel Bayesian rare variant Association Test using Integrated Nested Laplace Approximation (BATI). Unlike existing RVAS tests, BATI allows integration of individual or variant-specific features as covariates, while efficiently performing inference based on full model estimation. We demonstrate that BATI outperforms established RVAS methods on realistic, semi-synthetic whole-exome sequencing cohorts, especially when using meaningful biological context, such as functional annotation. We show that BATI achieves power above 70% in scenarios in which competing tests fail to identify risk genes, e.g. when risk variants in sum explain less than 0.5% of phenotypic variance. We have integrated BATI, together with five existing RVAS tests in the ‘Rare Variant Genome Wide Association Study’ (rvGWAS) framework for data analyzed by whole-exome or whole genome sequencing. rvGWAS supports rare variant association for genes or any other biological unit such as promoters, while allowing the analysis of essential functionalities like quality control or filtering. Applying rvGWAS to a Chronic Lymphocytic Leukemia study we identified eight candidate predisposition genes, including EHMT2 and COPS7A.
Neural oscillatory responses to performance monitoring differ between high‐ and low‐impulsive individuals, but are unaffected by TMS
2021-02-19

Abstract Higher impulsivity may arise from neurophysiological deficits of cognitive control in the prefrontal cortex. Cognitive control can be assessed by time‐frequency decompositions of electrophysiological data. We aimed to clarify neuroelectric mechanisms of performance monitoring in connection with impulsiveness during a modified Eriksen flanker task in high‐ ( n = 24) and low‐impulsive subjects ( n = 21) and whether these are modulated by double‐blind, sham‐controlled intermittent theta burst stimulation (iTBS). We found a larger error‐specific peri‐response beta power decrease over fronto‐central sites in high‐impulsive compared to low‐impulsive participants, presumably indexing less effective motor execution processes. Lower parieto‐occipital theta intertrial phase coherence (ITPC) preceding correct responses predicted higher reaction time (RT) and higher RT variability, potentially reflecting efficacy of cognitive control or general attention. Single‐trial preresponse theta phase clustering was coupled to RT in correct trials (weighted ITPC), reflecting oscillatory dynamics that predict trial‐specific behavior. iTBS did not modulate behavior or EEG time‐frequency power. Performance monitoring was associated with time‐frequency patterns reflecting cognitive control (parieto‐occipital theta ITPC, theta weighted ITPC) as well as differential action planning/execution processes linked to trait impulsivity (frontal low beta power). Beyond that, results suggest no stimulation effect related to response‐locked time‐frequency dynamics with the current stimulation protocol. Neural oscillatory responses to performance monitoring differ between high‐ and low‐impulsive individuals, but are unaffected by iTBS.
Successful Regression in Patients with Progressive Keratoconus by Corneal Crosslinking
2021-02-19

Abstract Background Since 2019, corneal collagen crosslinking (CXL) is included in the catalog of procedures covered by statutory health insurance in Germany. CXL is an established ophthalmological procedure for the last 20 years. The aim of this investigation was the measurement of progression before and after CXL. Material und Methods 65 consecutive eyes with progressive keratoconus from 53 patients were included in the retrospective study, which were observed at the University Eye Hospital Tübingen at least two years before and at least two years after CXL. The time of observation took place from October 2009 until March 2018. Parameters of interest had been the best corrected visual acuity (BCVA) and the keratometric values from the elevation maps measured by a Scheimpflug camera. Results 65 eyes of 53 patients had been documented. The study population included 46 (86.8%) male and 7 (13.2%) female subjects. The mean age was 24 ± 8 years. The averaged observation time between the primary consultation and CXL showed 25 ± 15 months. Preoperatively the mean BCVA pointed out in a significant increase (0.13 ± 0.17 [first visit] vs. 0.23 ± 0.22 [preOP], p &lt; 0.0001) while the mean Kmax resulted in a statistically significant increase (46.34 ± 3.33 dpt [first visit] vs. 48.78 ± 4.17 dpt [preOP], p &lt; 0.0001). The mean thinnest point of the cornea showed a significant decrease (490.48 ± 34.23 μm [first visit] vs. 468.62 ± 29.84 μm [preop], p &lt; 0.0001). Postoperatively the mean BCVA resulted in a significant improvement at the 12th postoperative month in comparison to the preoperative measurement (0.23 ± 0.22 [preOP] vs. 0.16 ± 0.14 [12 months], p = 0.04 respectively 0.17 ± 0.17 [24 months], p = 0.0006). The mean Kmax demonstrated in the 12th postoperative month a significant reduction (48.78 ± 4.17 dpt [preOP] vs. 47.91 ± 3.41 dpt [12 months], p = 0.0009 respectively 48 ± 4.56 dpt [24 months], p = 0.0051). The mean thinnest point of the cornea indicated a decrease at the 12th postoperative month (468.62 ± 29.84 μm [preOP] vs. 459.82 ± 35.88 μm [12 months], p = 0.0078 respectively 453.47 ± 43.39 μm [24 months], p = 0.0227). Conclusion CXL is a successful procedure for the therapy of progressive keratoconus.