julilili42/papers huggingface dataset:
Viral Myocarditis—From Pathophysiology to Treatment
2021-11-11

The diagnosis of acute and chronic myocarditis remains a challenge for clinicians. Characterization of this disease has been hampered by its diverse etiologies and heterogeneous clinical presentations. Most cases of myocarditis are caused by infectious agents. Despite successful research in the last few years, the pathophysiology of viral myocarditis and its sequelae leading to severe heart failure with a poor prognosis is not fully understood and represents a significant public health issue globally. Most likely, at a certain point, besides viral persistence, several etiological types merge into a common pathogenic autoimmune process leading to chronic inflammation and tissue remodeling, ultimately resulting in the clinical phenotype of dilated cardiomyopathy. Understanding the underlying molecular mechanisms is necessary to assess the prognosis of patients and is fundamental to appropriate specific and personalized therapeutic strategies. To reach this clinical prerequisite, there is the need for advanced diagnostic tools, including an endomyocardial biopsy and guidelines to optimize the management of this disease. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has currently led to the worst pandemic in a century and has awakened a special sensitivity throughout the world to viral infections. This work aims to summarize the pathophysiology of viral myocarditis, advanced diagnostic methods and the current state of treatment options.
Material Objects
2021-11-11

This Element is a survey of central topics in the metaphysics of material objects. The topics are grouped into four problem spaces. The first concerns how an object's parts are related to the object's existence and to the object's nature, or essence. The second concerns how an object persists through time, how an object is located in spacetime, and how an object changes. The third concerns paradoxes about objects, including paradoxes of coincidence, paradoxes of fission, and the problem of the many. The fourth concerns views with radical consequences regarding the existence of composite material objects, including mereological nihilism, ontological anti-realism, and deflationism.
Granzyme B: A Double-Edged Sword in the Response to Influenza Infection in Vaccinated Older Adults
2021-11-11

Background: Influenza-specific cytolytic T lymphocytes (CTL) have a critical role in clearing the virus from the lungs, but are poorly stimulated by current inactivated influenza vaccines. Our previous work suggests that granzyme B (GrB) activity predicts protection against laboratory-confirmed influenza infection (LCII) in older adults. However, basal GrB (bGrB) activity increases with age and the frequency of GrB + CTL that do not co-express perforin increases following influenza infection, thereby acting as a potential contributor to immune pathology. Objectives: Using data from a 4-years randomized trial of standard-versus high-dose influenza vaccination, we sought to determine whether measurements of GrB activity alone indicate a protective vs pathologic response to influenza infection. We compared LCII to No-LCII subsets according to: pre-vaccination bGrB activity; and induced GrB activity in ex vivo influenza-challenged peripheral blood mononuclear cells (PBMC) at four and 20weeks post-vaccination. Results: Over four influenza seasons (2014–2018), 27 of 608 adult participants aged 65 years and older developed influenza A/H3N2-LCII (n = 18) or B-LCII (n = 9). Pre-vaccination, there was a significant correlation between bGrB and ex vivo GrB activity in each of the H3N2-LCII, B-LCII, and No-LCII subsets. Although pre-vaccination ex vivo GrB activity was significantly higher in B-LCII vs No-LCII with a trend for H3N2-LCII vs No-LCII, there was no difference in the response to vaccination. In contrast, there was a trend toward increased pre-vaccination bGrB activity and LCII: Odds Ratio (OR) (95% confidence intervals) OR = 1.46 (0.94, 2.33). By 20-weeks post-vaccination, there were significant fold-increases in ex vivo GrB activity specific for the infecting subtype in H3N2-LCII: OR = 1.63 (1.35, 2.00) and B-LCII: OR = 1.73 (1.34, 2.23). Conclusions: Our results suggest that the poor GrB responses to influenza vaccination that led to development of LCII can be attributed to inactivated formulations rather than the aging immune system since LCII cases generated robust ex vivo GrB responses following natural infection. Further, we identified bGrB as a biomarker of those who remain at risk for LCII following vaccination. Future studies will focus on understanding the mechanisms responsible for the shift in GrB-mediated protection vs potential immune pathology caused by GrB release.
Next-generation phylogeography of the banded newts (Ommatotriton): A phylogenetic hypothesis for three ancient species with geographically restricted interspecific gene flow and deep intraspecific genetic structure
2021-11-11

Technological developments now make it possible to employ many markers for many individuals in a phylogeographic setting, even for taxa with large and complex genomes such as salamanders. The banded newt (genus Ommatotriton) from the Near East has been proposed to contain three species (O. nesterovi, O. ophryticus and O. vittatus) with unclear phylogenetic relationships, apparently limited interspecific gene flow and deep intraspecific geographic mtDNA structure. We use parallel tagged amplicon sequencing to obtain 177 nuclear DNA markers for 35 banded newts sampled throughout the range. We determine population structure (with Bayesian clustering and principal component analysis), interspecific gene flow (by determining the distribution of species-diagnostic alleles) and phylogenetic relationships (by maximum likelihood inference of concatenated sequence data and based on a summary-coalescent approach). We confirm that the three proposed species are genetically distinct. A sister relationship between O. nesterovi and O. ophryticus is suggested. We find evidence for introgression between O. nesterovi and O. ophryticus, but this is geographically limited. Intraspecific structuring is extensive, with the only recognized banded newt subspecies, O. vittatus cilicensis, representing the most distinct lineage below the species level. While mtDNA mostly mirrors the pattern observed in nuclear DNA, all banded newt species show mito-nuclear discordance as well.
Altered Proinflammatory Responses to Polyelectrolyte Multilayer Coatings Are Associated with Differences in Protein Adsorption and Wettability
2021-11-11

A full understanding of the relationship between surface properties, protein adsorption, and immune responses is lacking but is of great interest for the design of biomaterials with desired biological profiles. In this study, polyelectrolyte multilayer (PEM) coatings with gradient changes in surface wettability were developed to shed light on how this impacts protein adsorption and immune response in the context of material biocompatibility. The analysis of immune responses by peripheral blood mononuclear cells to PEM coatings revealed an increased expression of proinflammatory cytokines tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1β, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 and the surface marker CD86 in response to the most hydrophobic coating, whereas the most hydrophilic coating resulted in a comparatively mild immune response. These findings were subsequently confirmed in a cohort of 24 donors. Cytokines were produced predominantly by monocytes with a peak after 24 h. Experiments conducted in the absence of serum indicated a contributing role of the adsorbed protein layer in the observed immune response. Mass spectrometry analysis revealed distinct protein adsorption patterns, with more inflammation-related proteins (e.g., apolipoprotein A-II) present on the most hydrophobic PEM surface, while the most abundant protein on the hydrophilic PEM (apolipoprotein A-I) was related to anti-inflammatory roles. The pathway analysis revealed alterations in the mitogen-activated protein kinase (MAPK)-signaling pathway between the most hydrophilic and the most hydrophobic coating. The results show that the acute proinflammatory response to the more hydrophobic PEM surface is associated with the adsorption of inflammation-related proteins. Thus, this study provides insights into the interplay between material wettability, protein adsorption, and inflammatory response and may act as a basis for the rational design of biomaterials.
ODGI: understanding pangenome graphs
2021-11-11

Abstract Motivation Pangenome graphs provide a complete representation of the mutual alignment of collections of genomes. These models offer the opportunity to study the entire genomic diversity of a population, including structurally complex regions. Nevertheless, analyzing hundreds of gigabase-scale genomes using pangenome graphs is difficult as it is not well-supported by existing tools. Hence, fast and versatile software is required to ask advanced questions to such data in an efficient way. Results We wrote ODGI, a novel suite of tools that implements scalable algorithms and has an efficient in-memory representation of DNA pangenome graphs in the form of variation graphs. ODGI supports pre-built graphs in the Graphical Fragment Assembly format. ODGI includes tools for detecting complex regions, extracting pangenomic loci, removing artifacts, exploratory analysis, manipulation, validation, and visualization. Its fast parallel execution facilitates routine pangenomic tasks, as well as pipelines that can quickly answer complex biological questions of gigabase-scale pangenome graphs. Availability ODGI is published as free software under the MIT open source license. Source code can be downloaded from https://github.com/pangenome/odgi and documentation is available at https://odgi.readthedocs.io . ODGI can be installed via Bioconda https://bioconda.github.io/recipes/odgi/README.html or GNU Guix https://github.com/pangenome/odgi/blob/master/guix.scm . Contact egarris5@uthsc.edu
Strong coupling between an optical microcavity and photosystems in single living cyanobacteria
2021-11-11

Abstract The first step in photosynthesis is an extremely efficient energy transfer mechanism that led to the debate to which extent quantum coherence may be involved in the energy transfer between the photosynthetic pigments. In search of such a coherent behavior, we have embedded living cyanobacteria between the parallel mirrors of an optical microresonator irradiated with low intensity white light. As a consequence, we observe vacuum Rabi splitting in the transmission and fluorescence spectra as a result of strong light matter coupling of the chlorophyll a molecules in the photosystems (PSs) and the cavity modes. The Rabi‐splitting scales with the number of the PSs chlorophyll a pigments involved in strong coupling indicating a delocalized polaritonic state. Our data provide evidence that a delocalized polaritonic state can be established between the chlorophyll a molecule of the PSs in living cyanobacterial cells at ambient conditions in a microcavity.
Association of professional pre-qualifications, study success in medical school and the eligibility for becoming a physician: A scoping review
2021-11-11

Background Literature, individual experiences and common considerations suggest that prior professional qualification can be an advantage for later career development. For instance, in Germany, professional pre-qualification has been honored by medical faculties in selection procedures for several years. However, a systematic evaluation of this relationship lacks. This scoping review summarizes existing literature and addresses the role of prior professional pre-qualifications on objective or subjective study success and the choice of a specialization. Methods The scoping review was performed oriented on the PRISMA guidelines. PsycINFO and PubMed databases were searched for relevant studies that included data of medical students with and without professional pre-qualifications. To answer the underlying research questions, this scoping review also includes studies that examine professional pre-qualifications in association with non-cognitive "soft" criteria. Results and further directions 1055 items were identified and reviewed by two independent reviewers with final 11 studies were included for this scoping review. The results of identified studies that report possible effects of prior pre-professional qualifications are inconclusive but suggest that prior professional qualifications tend not to have rather an advantage on study success. Medical school success for students with prior professional qualifications tended to be below average in the preclinical setting, and there were no differences in the clinical setting compared with students without prior professional qualifications. The influence of professional pre-qualifications has not yet been adequately studied without the moderator variable “waiting time” and “A-levels grade”. The scoping review indicates insufficient number of articles stating a co-relation of prior pre-qualifications and subjective data. Again, the results found are not sufficient to state a clear relationship between professional pre-qualifications and the choice of a specific speciality preference. However, professional pre-qualifications, both in medicine and as "practical experience in rural areas", tend to be beneficial for the choice of becoming a rural physician. Large-scale cross-sectional and longitudinal studies are needed to investigate the influence of professional pre-qualifications on different study trajectory parameters.
A quantitative paleoclimatic reconstruction of the non-analogue environment of oxygen isotope stage 3: new data from small mammal records of southwestern Germany
2021-11-11

Abstract Ensuring comparability between results is a key goal of all paleoecological reconstructions. Quantitative estimates of meteorological variables, as opposed to relative qualitative descriptions, provide the opportunity to compare local paleoenvironmental records against global estimates and incrementally build regional paleoclimatic records. The Bioclimatic Method provides quantitative and qualitative estimates of past landscape composition and climate along with measures of statistical accuracy by applying linear discriminant functions analysis and transfer functions to faunal taxonomic abundance data. By applying this method to the rodent data from Geißenklösterle and Hohle Fels, two Paleolithic cave sites located in the Ach Valley of southwestern Germany, we classify the regional vegetation according to Walters’ zonobiome model. We also present new estimates of meteorological variables including mean annual temperature, mean annual precipitation, and vegetative activity period of the Ach Valley for the period spanning ~ 60,000 to 35,000 cal BP. The results suggest the Ach Valley contained a non-analogous landscape of arctic tundra and temperate deciduous woodland with occasional arid steppe expansion. Meteorological estimates suggest the climate was significantly colder during the Middle and Upper Paleolithic than today, with higher annual precipitation and dramatic temperature shifts between seasons. These results fit well with climatic reconstructions from Switzerland and the Netherlands based on a variety of proxies. They also provide further evidence of a localized climatic response within southwestern Germany to the stadial-interstadial shifts preceding the Heinrich 4 event. Finally, these results reinforce our previous claims that climatic volatility was not a driving force in the loss of Neanderthal groups throughout the Swabian Jura during OIS 3.
Sex determination accuracy using the human sacrum in a Central European sample
2021-11-11

The sacrum is often used for sex estimation of human remains. However, reported sexual classification accuracies based on the sacrum produce highly discrepant estimates ranging from 54% to 98% depending on the method and reference sample. Here, we therefore aim to evaluate the sacrum's efficacy in differentiating males from females by comparing three different approaches in a homogeneous Central European sample (n = 58, 27 males and 31 females) obtained from the 19th century Weisbach collection. Specifically, we investigated the sacrum by 1) a qualitative visual inspection, 2) traditional linear metrics, namely, sacral width, corpus width, and the associated corporo-basal index, and 3) geometric morphometrics (GM) using a 3D configuration of 100 landmarks and semilandmarks. Classification accuracies for the qualitative approach ranged from 69% to 81%. The investigated quantitative methods based on linear dimensions led to comparable classification accuracies of 62% for sacral width and 78% for the corporo-basal index. However, absolute corpus width had a stronger discriminative power (86%), similar to the PC scores from shape space (87%). Unexpectedly, the GM approach, which considered the shape of the entire sacrum, did not classify better than linear variables. This was exceeded only when sacrum shape was combined with corpus width or another measure of size, like the natural logarithm of the centroid size, yielding a classification accuracy of 95%. The male and female group means differed mainly in the general height-to-width relationship and corpus-to-alae proportions, corroborating patterns previously described in the literature. Our results suggest that the sacrum is markedly less effective than the hipbone for sex determination, which is at odds with its central position within the pelvic girdle and thus its supposed obstetric relevance.
Effective cell membrane tension is independent of polyacrylamide substrate stiffness
2021-11-11

Abstract Most animal cells are surrounded by a cell membrane and an underlying actomyosin cortex. Both structures are linked, and they are under tension. In-plane membrane tension and cortical tension both influence many cellular processes, including cell migration, division, and endocytosis. However, while actomyosin tension is regulated by substrate stiffness, how membrane tension responds to mechanical substrate properties is currently poorly understood. Here, we probed the effective membrane tension of neurons and fibroblasts cultured on glass and polyacrylamide substrates of varying stiffness using optical tweezers. In contrast to actomyosin-based traction forces, both peak forces and steady state tether forces of cells cultured on hydrogels were independent of substrate stiffness and did not change after blocking myosin II activity using blebbistatin, indicating that tether and traction forces are not directly linked. Peak forces in fibroblasts on hydrogels were about twice as high as those in neurons, indicating stronger membrane-cortex adhesion in fibroblasts. Steady state tether forces were generally higher in cells cultured on hydrogels than on glass, which we explain by a mechanical model. Our results provide new insights into the complex regulation of effective membrane tension and pave the way for a deeper understanding of the biological processes it instructs.
Characterizing X‐ray activity cycles of young solar‐like stars with solar observations
2021-11-11

Abstract Throughout an activity cycle, magnetic structures rise to the stellar surface, evolve, and decay. Tracing their evolution on a stellar corona allows us to characterize the X‐ray cycles. However, directly mapping magnetic structures is feasible only for the Sun, while such structures are spatially unresolved with present‐day X‐ray instruments on stellar coronae. We present here a new method, implemented by us, that indirectly reproduces the stellar X‐ray spectrum and its variability with solar magnetic structures. The technique converts solar corona observations into a format identical to that of stellar X‐ray observations and, specifically, spectra of the X‐ray satellite XMM‐Newton . From matching these synthetic spectra with those observed for a star of interest, a fractional surface coverage with solar magnetic structures can be associated to each X‐ray observation. We apply this method to two young solar‐like stars: Eri ( Myr), the youngest star to display a coronal cycle ( yr), and Kepler 63 ( Myr), for which the X‐ray monitoring did not reveal a cyclic variability. We found that even during the cycle minimum a large portion of Eri's corona is covered with active structures. Therefore, there is little space for additional magnetic regions during the maximum, explaining the small observed cycle amplitude ( ) in terms of the X‐ray luminosity. Kepler 63 displays an even higher coverage with magnetic structure than the corona of Eri. This supports the hypothesis that for stars younger than Myr the X‐ray cycles are inhibited by a massive presence of coronal regions.
The limits of automatic sensorimotor processing during word processing: Investigations with repeated linguistic experience, memory consolidation during sleep, and rich linguistic learning contexts
2021-11-11

While a number of studies have repeatedly demonstrated an automatic activation of sensorimotor experience during language processing in the form of action-congruency effects, as predicted by theories of grounded cognition, more recent research has not found these effects for words that were just learned from linguistic input alone, without sensorimotor experience with their referents. In the present study, we investigate whether this absence of effects can be attributed to a lack of repeated experience and consolidation of the associations between words and sensorimotor experience in memory. To address these issues, we conducted four experiments in which (1 and 2) participants engaged in two separate learning phases in which they learned novel words from language alone, with an intervening period of memory-consolidating sleep, and (3 and 4) we employed familiar words whose referents speakers have no direct experience with (such as plankton). However, we again did not observe action-congruency effects in subsequent test phases in any of the experiments. This indicates that direct sensorimotor experience with word referents is a necessary requirement for automatic sensorimotor activation during word processing.
Imaging of Electrothermal Filament Formation in a Mott Insulator
2021-11-12

Resistive switching—the current- and voltage-induced change of electrical resistance—is at the core of memristive devices, which play an essential role in the emerging field of neuromorphic computing. This study is about resistive switching in a Mott insulator, which undergoes a thermally driven metal-to-insulator transition. Two distinct switching mechanisms are reported for such a system: electric-field-driven resistive switching and electrothermal resistive switching. The latter results from an instability caused by Joule heating. Here, we present the visualization of the reversible resistive switching in a planar V&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; thin-film device using high-resolution wide-field microscopy in combination with electric transport measurements. We investigate the interaction of the electrothermal instability with the strain-induced spontaneous phase separation in the V&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; thin film at the Mott transition. The photomicrographs show the formation of a narrow metallic filament with a minimum width ≲500 nm. Although the filament formation and the overall shape of the current-voltage characteristics (IVCs) are typical of an electrothermal breakdown, we also observe atypical effects such as oblique filaments, filament splitting, and hysteretic IVCs with sawtoothlike jumps at high currents in the low-resistance regime. We are able to reproduce the experimental results in a numerical model based on a two-dimensional resistor network. This model demonstrates that resistive switching in this case is indeed electrothermal and that the intrinsic heterogeneity is responsible for the atypical effects. This heterogeneity is strongly influenced by strain, thereby establishing a link between switching dynamics and structural properties.