julilili42/papers huggingface dataset:
Differential kinetics of T cell and antibody responses delineate dominant T cell epitopes in long-term immunity after COVID-19
2020-11-25

Abstract Long-term immunity to SARS-CoV-2 is crucial for the development of herd immunity and the aim of vaccination approaches. Reports on rapidly decreasing antibody titers question the efficacy of humoral immunity. The relevance of T cell memory after COVID-19 is yet unclear. Longitudinal analysis of SARS-CoV-2 immunity in convalescents up to six months post-infection revealed decreasing and stable spike and nucleocapsid antibody responses, respectively. In contrast, T cell responses remained robust and even increased in frequency and intensity. Single epitope mapping of T cell diversity over time identified ORF-independent, dominant T cell epitopes mediating long-term SARS-CoV-2 T cell responses and may be fundamental for vaccine design.
A consistency account of advice taking: Integrating the effects of advice consensus and advice distance
2020-11-25

&lt;p&gt;Which factors determine how individuals utilize advice? Previous research focused on either the consensus or the proximity of advice. We develop a general account of advice taking, arguing that both consensus and proximity influence the consistency (or variance) of the information on hand. From this account, we derive a number of predictions regarding the effects of consensus, distance, and amount of advice on confidence, judgment revision, and advice weighting. Across three experiments, we orthogonally manipulated the distance and consensus of advice. The amount of advice was either measured (Experiments 1 and 2) or manipulated (Experiment 3). The results provide strong support for our consistency account of advice taking. It allows explaining a complex pattern of findings that neither consensus nor proximity alone can account for. This research advances our theoretical understanding of advice taking, while adding to a broader literature that highlights the importance of consistency of information for judgment and decision making.&lt;/p&gt;
A one health framework to estimate the cost of antimicrobial resistance
2020-11-26

Abstract Objectives/purpose The costs attributable to antimicrobial resistance (AMR) remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR across human, animal, and environmental health; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network has developed a framework to help guide AMR costing exercises in any part of the world as a first step towards more comprehensive analyses for comparing AMR interventions at the local level as well as more harmonized analyses for quantifying the full economic burden attributable to AMR at the global level. Methods GAP-ON€ (funded under the JPIAMR 8th call (Virtual Research Institute) is composed of 19 international networks and institutions active in the field of AMR. For this project, the Network operated by means of Delphi rounds, teleconferences and face-to-face meetings. The resulting costing framework takes a bottom-up approach to incorporate all relevant costs imposed by an AMR bacterial microbe in a patient, in an animal, or in the environment up through to the societal level. Results The framework itemizes the epidemiological data as well as the direct and indirect cost components needed to build a realistic cost picture for AMR. While the framework lists a large number of relevant pathogens for which this framework could be used to explore the costs, the framework is sufficiently generic to facilitate the costing of other resistant pathogens, including those of other aetiologies. Conclusion In order to conduct cost-effectiveness analyses to choose amongst different AMR-related interventions at local level, the costing of AMR should be done according to local epidemiological priorities and local health service norms. Yet the use of a common framework across settings allows for the results of such studies to contribute to cumulative estimates that can serve as the basis of broader policy decisions at the international level such as how to steer R&amp;D funding and how to prioritize AMR amongst other issues. Indeed, it is only by building a realistic cost picture that we can make informed decisions on how best to tackle major health threats.
The Many Faces of DFNB9: Relating OTOF Variants to Hearing Impairment
2020-11-26

The OTOF gene encodes otoferlin, a critical protein at the synapse of auditory sensory cells, the inner hair cells (IHCs). In the absence of otoferlin, signal transmission of IHCs fails due to impaired release of synaptic vesicles at the IHC synapse. Biallelic pathogenic and likely pathogenic variants in OTOF predominantly cause autosomal recessive profound prelingual deafness, DFNB9. Due to the isolated defect of synaptic transmission and initially preserved otoacoustic emissions (OAEs), the clinical characteristics have been termed “auditory synaptopathy”. We review the broad phenotypic spectrum reported in patients with variants in OTOF that includes milder hearing loss, as well as progressive and temperature-sensitive hearing loss. We highlight several challenges that must be addressed for rapid clinical and genetic diagnosis. Importantly, we call for changes in newborn hearing screening protocols, since OAE tests fail to diagnose deafness in this case. Continued research appears to be needed to complete otoferlin isoform expression characterization to enhance genetic diagnostics. This timely review is meant to sensitize the field to clinical characteristics of DFNB9 and current limitations in preparation for clinical trials for OTOF gene therapies that are projected to start in 2021.
MIRACLES: atmospheric characterization of directly imaged planets and substellar companions at 4–5 μm
2020-11-26

The circumstellar disk of PDS 70 hosts two forming planets, which are actively accreting gas from their environment. The physical and chemical characteristics of these planets remain ambiguous due to their unusual spectral appearance compared to more evolved objects. In this work, we report the first detection of PDS 70 b in the Br α and M ′ filters with VLT/NACO, a tentative detection of PDS 70 c in Br α , and a reanalysis of archival NACO L ′ and SPHERE H 23 and K 12 imaging data. The near side of the disk is also resolved with the Br α and M ′ filters, indicating that scattered light is non-negligible at these wavelengths. The spectral energy distribution (SED) of PDS 70 b is well described by blackbody emission, for which we constrain the photospheric temperature and photospheric radius to T eff = 1193 ± 20 K and R = 3.0 ± 0.2 R J . The relatively low bolometric luminosity, log( L ∕ L ⊙ ) = −3.79 ± 0.02, in combination with the large radius, is not compatible with standard structure models of fully convective objects. With predictions from such models, and adopting a recent estimate of the accretion rate, we derive a planetary mass and radius in the range of M p ≈ 0.5–1.5 M J and R p ≈ 1–2.5 R J , independently of the age and post-formation entropy of the planet. The blackbody emission, large photospheric radius, and the discrepancy between the photospheric and planetary radius suggests that infrared observations probe an extended, dusty environment around the planet, which obscures the view on its molecular composition. Therefore, the SED is expected to trace the reprocessed radiation from the interior of the planet and/or partially from the accretion shock. The photospheric radius lies deep within the Hill sphere of the planet, which implies that PDS 70 b not only accretes gas but is also continuously replenished by dust. Finally, we derive a rough upper limit on the temperature and radius of potential excess emission from a circumplanetary disk, T eff ≲ 256 K and R ≲ 245 R J , but we do find weak evidence that the current data favors a model with a single blackbody component.
Decision-making skills of high-performance youth soccer players
2020-11-26

Abstract Objectives This study aimed to develop a valid video-based diagnostic instrument that assesses decision-making with a sport-specific motor response. Methods A total of 86 German youth academy players (16.7 ± 0.9 years) viewed game situations projected on a large video screen and were required to make a decision by dribbling and passing to one of three targets (representing different decision options). The test included 48 clips separated into two categories: build-up (bu) and offensive decisions (off). Criterion-related validity was tested based on age (i.e., U16, U17, and U19), playing status (i.e., minutes played in official matches of the current season) and in a prospective approach relating to future youth national team status (i.e., selected or nonselected). Finally, it was investigated whether decision-making competence was influenced by playing position (i.e., defenders vs. midfielders vs. forwards). Results Instrumental reliability demonstrated satisfactory values for SC bu ( r = 0.72), and lower for SC off ( r = 0.56). Results showed the diagnostic instrument is suitable for discriminating between playing status (SC bu : Φ = 0.22, p &lt; 0.01; SC off : Φ = 0.14, p &lt; 0.05) and between younger (U16) and older players (U17 &gt; U16 in SC bu : Φ = 0.24 and SC off : Φ = 0.39, p &lt; 0.01; U19 &gt; U16 in SC bu : Φ = 0.41 and SC off : Φ = 0.46, p &lt; 0.01); however, there was no difference between U17 and U19 players. Furthermore, the predictive value of the test indicates that future youth national team players make better decisions with respect to the build-up category (SC bu : Φ = 0.20; p &lt; 0.05), whereas playing position did not significantly influence decision-making competence. Conclusion Results indicate the video-based decision-making diagnostic instrument can discriminate decision-making competence within a high-performance youth group. The outcomes associated with national youth team participation demonstrate the predictive value of the diagnostic instrument. This study provides initial evidence to suggest a new video-based diagnostic instrument with a soccer-specific motor response can be used within a talent identification process to assist with assessment of decision-making performance.
First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy – a case report
2020-11-26

Abstract Background Dominant optic atrophy (DOA) is an inherited optic neuropathy that mainly affects visual acuity, central visual fields and color vision due to a progressive loss of retinal ganglion cells and their axons that form the optic nerve. Approximately 45–90% of affected individuals with DOA harbor pathogenic variants in the OPA1 gene. The mutation spectrum of OPA1 comprises nonsense, canonical and non-canonical splice site, frameshift and missense as well as copy number variants, but intragenic inversions have not been reported so far. Case presentation We report a 33-year-old male with characteristic clinical features of DOA. Whole-genome sequencing identified a structural variant of 2.4 kb comprising an inversion of 937 bp at the OPA1 locus. Fine mapping of the breakpoints to single nucleotide level revealed that the structural variation was an inversion flanked by two deletions. As this rearrangement inverts the entire first exon of OPA1 , it was classified as likely pathogenic. Conclusions We report the first DOA case harboring an inversion in the OPA1 gene. Our study demonstrates that copy-neutral genomic rearrangements have to be considered as a possible cause of disease in DOA cases.
Control of Complement Activation by the Long Pentraxin PTX3: Implications in Age-Related Macular Degeneration
2020-11-26

Dysregulation of the complement system is central to age-related macular degeneration (AMD), the leading cause of blindness in the developed world. Most of the genetic variation associated with AMD resides in complement genes, with the greatest risk associated with polymorphisms in the complement factor H ( CFH ) gene; factor H (FH) is the major inhibitor of the alternative pathway (AP) of complement that specifically targets C3b and the AP C3 convertase. Long pentraxin 3 (PTX3) is a soluble pattern recognition molecule that has been proposed to inhibit AP activation via recruitment of FH. Although present in the human retina, if and how PTX3 plays a role in AMD is still unclear. In this work we demonstrated the presence of PTX3 in the human vitreous and studied the PTX3-FH-C3b crosstalk and its effects on complement activation in a model of retinal pigment epithelium (RPE). RPE cells cultured in inflammatory AMD-like conditions overexpressed the PTX3 protein, and up-regulated AP activating genes. PTX3 bound RPE cells in a physiological setting, however this interaction was reduced in inflammatory conditions, whereby PTX3 had no complement-inhibiting activity on inflamed RPE. However, on non-cellular surfaces, PTX3 formed a stable ternary complex with FH and C3b that acted as a “hot spot” for complement inhibition. Our findings suggest a protective role for PTX3 in response to complement dysregulation in AMD and point to a novel mechanism of complement regulation by this pentraxin with potential implications in pathology and pharmacology of AMD.
Optimizing the Process Efficiency of Reactive Extrusion in the Synthesis of Vinyltrimethoxysilane-Grafted Ethylene-Octene-Copolymer (EOC-g-VTMS) by Response Surface Methodology
2020-11-26

Thermoplastic polymers like ethylene-octene copolymer (EOC) may be grafted with silanes via reactive extrusion to enable subsequent crosslinking for advanced biomaterials manufacture. However, this reactive extrusion process is difficult to control and it is still challenging to reproducibly arrive at well-defined products. Moreover, high grafting degrees require a considerable excess of grafting reagent. A large proportion of the silane passes through the process without reacting and needs to be removed at great expense by subsequent purification. This results in unnecessarily high consumption of chemicals and a rather resource-inefficient process. It is thus desired to be able to define desired grafting degrees with optimum grafting efficiency by means of suitable process control. In this study, the continuous grafting of vinyltrimethoxysilane (VTMS) on ethylene-octene copolymer (EOC) via reactive extrusion was investigated. Successful grafting was verified and quantified by 1H-NMR spectroscopy. The effects of five process parameters and their synergistic interactions on grafting degree and grafting efficiency were determined using a face-centered experimental design (FCD). Response surface methodology (RSM) was applied to derive a causal process model and define process windows yielding arbitrary grafting degrees between &lt;2 and &gt;5% at a minimum waste of grafting agent. It was found that the reactive extrusion process was strongly influenced by several second-order interaction effects making this process difficult to control. Grafting efficiencies between 75 and 80% can be realized as long as grafting degrees &lt;2% are admitted.
Stability of Smyd1 in endothelial cells is controlled by PML-dependent SUMOylation upon cytokine stimulation
2020-11-26

Smyd1 is an epigenetic modulator of gene expression that has been well-characterized in muscle cells. It was recently reported that Smyd1 levels are modulated by inflammatory processes. Since inflammation affects the vascular endothelium, this study aimed to characterize Smyd1 expression in endothelial cells. We detected Smyd1 in human endothelial cells (HUVEC and EA.hy926 cells), where the protein was largely localized in PML nuclear bodies (PML-NBs). By transfection of EA.hy926 cells with expression vectors encoding Smyd1, PML, SUMO1, active or mutant forms of the SUMO protease SuPr1 and/or the SUMO-conjugation enzyme UBC9, as well as Smyd1- or PML-specific siRNAs, in the presence or absence of the translation blocker cycloheximide or the proteasome-inhibitor MG132, and supported by computational modeling, we show that Smyd1 is SUMOylated in a PML-dependent manner and thereby addressed for degradation in proteasomes. Furthermore, transfection with Smyd1-encoding vectors led to PML up-regulation at the mRNA level, while PML transfection lowered Smyd1 protein stability. Incubation of EA.hy926 cells with the pro-inflammatory cytokine TNF-α resulted in a constant increase in Smyd1 mRNA and protein over 24 h, while incubation with IFN-γ induced a transient increase in Smyd1 expression, which peaked at 6 h and decreased to control values within 24 h. The IFN-γ-induced increase in Smyd1 was accompanied by more Smyd1 SUMOylation and more/larger PML-NBs. In conclusion, our data indicate that in endothelial cells, Smyd1 levels are regulated through a negative feedback mechanism based on SUMOylation and PML availability. This molecular control loop is stimulated by various cytokines.
Different contrast encoding in ON and OFF visual pathways
2020-11-26

Abstract Subjective visual experience builds on sensory encoding of light reflected by different objects in our environment. Most retinal ganglion cells encode changes in light intensity, quantified as contrast, rather than the absolute intensity. Mathematically, contrast is often defined as a relative change in light intensity. Activity in the visual system and perceptual responses are usually explained with such definitions of contrast. Here, for the first time, we explicitly explored how contrast is actually represented in the visual system. Using mouse retina electrophysiology, we show that response strength of OFF retinal ganglion cells does not represent relative, but absolute changes in light intensity. ON RGC response strength is governed by a combination of absolute and relative change in light intensity. This is true for a wide range of ambient light levels, at least from scotopic to high mesopic regimes. Consequently, light decrements and increments are represented asymmetrically in the retina, which may explain the asymmetries in responses to negative and positive contrast observed throughout the visual system. These findings may help to more thoroughly design and interpret vision science studies where responses are driven by contrast of the visual stimuli.
Regulation of plasma aldosterone during hemodialysis
2020-11-26

In order to clarify the influence of serum potassium, serum sodium and plasma angiotensin II concentrations on aldosterone release during hemodialysis (HD), six chronic hemodialysis patients were studied during HD with varying dialysate sodium concentrations and different buffers. Plasma aldosterone concentrations were higher during acetate than bicarbonate HD, during low sodium compared to high sodium HD, and were correlated inversely to serum sodium concentrations. The decline in plasma aldosterone concentrations during HD paralleled the decrease in serum potassium concentrations, and plasma aldosterone concentrations were correlated with serum potassium concentrations. In addition, plasma aldosterone and plasma angiotensin II concentrations were correlated significantly. It is proposed that serum potassium and the renin-angiotensin system are the main factors of aldosterone release during hemodialysis, while serum sodium per se seems to be of less importance. The dialysate buffer employed also plays a role in aldosterone regulation (via the renin-angiotensin system).
P4-Protect
2020-11-26

1+1 protection is a method to secure traffic between two nodes against failures in between. The sending node duplicates the traffic and forwards it over two disjoint paths. The receiving node assures that only a single copy of the traffic is further forwarded to its destination. In contrast to other protection schemes, this method prevents almost any packet loss in case of failures. 1+1 protection is usually applied on the optical layer, on Ethernet, or on MPLS.
Midline Suboccipital Subtonsillar Approach in Semisitting Position for Resection of Jugular Tubercle Meningioma: 2-Dimensional Operative Video
2020-11-26

Abstract We present a case of a large jugular tubercle meningioma that was removed through a midline suboccipital subtonsillar approach in semisitting position. The patient is a 49-year-old woman with chronic, medication-resistant cephalgias but devoid of any subjective focal neurological deficit. On magnetic resonance imaging (MRI), an extra-axial lesion, originating from the left jugular tubercle was discovered. There was significant obliteration of the peripontine cisternal space, and compression of the adjacent pontomedullary junction; the lesion also extended into the left jugular foramen. On physical exam, an absent gag reflex was noted on the left, as well as a moderate deviation of the uvula to the contralateral side (partial Vernet's syndrome). A gross-total resection was achieved, histopathology confirmed a World Health Organization (WHO) grade I angiomatous meningioma with a low-proliferation index. The patient was discharged home 4 days after surgery with intact function of the lower cranial nerves (CN) following immediate and complete resolution of the preexisting partial CNs IX and X deficits. At 2-year follow-up, there was no indication of intradural residual or recurrence. In summary, the midline suboccipital subtonsillar approach is a simple and effective tool with limited morbidity in the armamentarium for the microsurgical management of pathologies residing in the posterior cranial fossa or the craniocervical junction. Major limitations exist for lesions extending above the internal acoustic canal or those of fibrous consistence featuring widespread adhesion to the ventral brainstem or vascular encasement. Provided the necessary anesthesiological precautions and intraoperative procedures the semisitting position is safe and effective. The link to the video can be found at: https://youtu.be/bbVXagwhDCo.
Persisting Neutralizing Activity to SARS-CoV-2 over Months in Sera of COVID-19 Patients
2020-11-27

The relationship between the nasopharyngeal virus load, IgA and IgG antibodies to both the S1-RBD-protein and the N-protein, as well as the neutralizing activity (NAbs) against SARS-CoV-2 in the blood of moderately afflicted COVID-19 patients, needs further longitudinal investigation. Several new serological methods to examine these parameters were developed, validated and applied in three patients of a family which underwent an ambulatory course of COVID-19 for six months. The virus load had almost completely disappeared after about four weeks. Serum IgA levels to the S1-RBD-protein and, to a lesser extent, to the N-protein, peaked about three weeks after clinical disease onset but declined soon thereafter. IgG levels rose continuously, reaching a plateau at approximately six weeks, and stayed elevated over the observation period. Virus-neutralizing activity reached a peak about 4 weeks after disease onset but dropped slowly. The longitudinal associations of virus neutralization and the serological immune response suggest immunity in patients even after a mild clinical course of COVID-19.