julilili42/papers huggingface dataset:
Heritability of Magnetoencephalography Phenotypes Among Patients With Genetic Generalized Epilepsy and Their Siblings
2021-05-27

Objective To assess whether neuronal signals in patients with genetic generalized epilepsy (GGE) are heritable, we examined magnetoencephalography resting-state recordings in patients and their healthy siblings. Methods In a prospective, cross-sectional design, we investigated source-reconstructed power and functional connectivity in patients, siblings, and controls. We analyzed 5 minutes of cleaned and awake data without epileptiform discharges in 6 frequency bands (1–40 Hz). We further calculated intraclass correlations to estimate heritability for the imaging patterns within families. Results Compared with controls (n = 45), patients with GGE (n = 25) showed widespread increased functional connectivity (θ to γ frequency bands) and power (δ to γ frequency bands) across the spectrum. Siblings (n = 18) fell between the levels of patients and controls. Heritability of the imaging metrics was observed in regions where patients strongly differed from controls, mainly in β frequencies, but also for δ and θ power. Network connectivity in GGE was heritable in frontal, central, and inferior parietal brain areas and power in central, temporo-parietal, and subcortical structures. Presence of generalized spike-wave activity during recordings and medication were associated with the network patterns, whereas other clinical factors such as age at onset, disease duration, or seizure control were not. Conclusion Metrics of brain oscillations are well suited to characterize GGE and likely relate to genetic factors rather than the active disease or treatment. High power and connectivity levels co-segregated in patients with GGE and healthy siblings, predominantly in the β band, representing an endophenotype of GGE.
Measurement invariance testing of the patient health questionnaire-9 (PHQ-9) across people with and without diabetes mellitus from the NHANES, EMHS and UK Biobank datasets
2021-05-27

Results provide support for measurement invariance between groups of people with and without diabetes, using either a one-factor or a two-factor model. While the two-factor solution has a slightly better fit, the one-factor solution is more parsimonious. Depending on research or clinical needs, both factor structures can be used.
Vesicle traffic in the outer hair cell
2021-05-27

Abstract The plasma‐membrane marker FM1‐43 was employed to reveal the relative significance of different types of endocytic and transcytic mechanisms in outer hair cells (OHCs) of the guinea‐pig cochlea. A double‐barrel local perfusion system was used to label independently the apical or synaptic pole of the isolated OHC to study mechanisms of vesicle uptake at the poles and of vesicle trafficking along and across the cell. Treatment with an inhibitor of macropino‐ and phagocytosis, phenylarsine oxide, or of clathrin‐mediated endocytic activity, concanavalin A, significantly reduced the dye uptake at both the apical and the synaptic poles, indicating the presence of both clathrin‐independent and clathrin‐mediated processes at both poles. However, measurement of uptake speed in the presence of the inhibitors suggested that clathrin‐independent processes contribute more extensively to endocytosis at the basal pole than the apical pole. Treatment with an inhibitor of myosin VI, 2,4,6‐triiodophenol, significantly delayed both the apicobasal and the basoapical fluorescence signals. However, treatment with an inhibitor of kinesin, monastrol, or of dynein, ciliobrevin D, significantly delayed the signals only in the basoapical direction. The myosinVI inhibitor, but neither the kinesin nor dynein inhibitors, significantly delayed the signals to the subsurface cisternae. That is, myosin VI carries vesicles in both longitudinal directions as well as radially to the subsurface cisternae, whereas kinesin and dynein participate primarily in basoapical trafficking. This fundamental information is essential for elucidating recycling mechanisms of specific proteins involved in establishing, controlling and maintaining the electromechanical action of OHCs and, therefore, is vital for understanding auditory perception.
Pembrolizumab for the treatment of renal cell carcinoma
2021-05-27

Immunotherapy has become the backbone for the treatment of advanced RCC. With the approval of several therapeutic options, research needs now to focus on defining the appropriate therapy for each patient. Axitinib plus pembrolizumab belongs to the combinations of tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors for the first-line treatment of metastatic RCC. New combinations of pembrolizumab plus TKI for the evaluation in first- and second-line treatment of mRCC available. However, studies directly comparing the various treatment regimens using predictive biomarkers and long-term endpoints, including treatment-free survival, are lacking.
Response and Oil Degradation Activities of a Northeast Atlantic Bacterial Community to Biogenic and Synthetic Surfactants
2021-05-27

Abstract Background: Biosurfactants, however, are naturally derived products that play a similar role to synthetic dispersants in oil spill response but are easily biodegradable and less toxic. Using a combination of analytical chemistry, 16S rRNA amplicon sequencing and simulation-based approaches, this study investigated the microbial community dynamics, ecological drivers, functional diversity and robustness, and oil biodegradation potential of a northeast Atlantic marine microbial community to crude oil when exposed to rhamnolipid or synthetic dispersant Finasol OSR52. Results: Psychrophilic Colwellia and Oleispira dominated the community in both the rhamnolipid and Finasol OSR52 treatments initially but later community structure across treatments diverged significantly: Rhodobacteraceae and Vibrio dominated the Finasol-amended treatment, whereas Colwellia , Oleispira , and later Cycloclasticus and Alcanivorax , dominated the rhamnolipid-amended treatment. The key aromatic hydrocarbon-degrading bacteria like Cycloclasticus was not observed in the Finasol treatment but it was abundant in the oil-only and rhamnolipid-amended treatments. Overall, Finasol had a significant negative impact on the community diversity, weakened the taxa-functional robustness of the community, and caused a stronger environmental filtering, more so than oil-only and rhamnolipid-amended oil treatments. Rhamnolipid-amended and oil-only treatments had the highest functional diversity, however, the overall oil biodegradation was greater in the Finasol treatment, but aromatic biodegradation was highest in the rhamnolipid treatment. Conclusion: Overall, the natural marine microbial community in the northeast Atlantic responded differently to crude oil dispersed with either synthetic or biogenic surfactants over time, but oil degradation was more enhanced by the synthetic dispersant. Collectively, our results advance the understanding of how rhamnolipid biosurfactants and synthetic dispersant Finasol affect the natural marine microbial community in the FSC, supporting their potential application in oil spills.
New euchromatic variant dup(11)(p15.3p15.1) transmitted through two generations defined by low coverage whole genome sequencing
2021-05-27

Abstract We report on a 14‐year old boy, his father, and his paternal uncle, all three carriers of a duplication of chromosomal region 11p15.3‐p15.1. The aberration was transmitted by the grandmother, who is carrier of a balanced insertion 46,XX,ins(14;11)(q32.1;p15.3p15.1). In order to determine the precise molecular basis of this structural variant, we performed low‐coverage whole genome sequencing on the boy's father. This approach allowed precise determination of the genomic breakpoints and revealed a duplication of 6.9 Mb, centromeric to the Beckwith–Wiedemann/Silver–Russell syndrome critical region in 11p15.5, that inserted in inverse orientation into 14q32.12 (according to HGVS nomenclature: NC_000014.8:g.92871000_92871001ins[NC_000011.9:g.12250642_19165928inv;T]). To our knowledge, this is the first report of a duplication of 11p15.3‐p15.1 involving more than 40 genes and transmitted through two generations without apparent clinical effects.
Default Negation as Explicit Negation plus Update
2021-05-27

We argue that under the stable model semantics default negation can be read as explicit negation with update. We show that dynamic logic programming which is based on default negation, even in the heads, can be interpreted in a variant of updates with explicit negation only. As corollaries, we get an easy description of default negation in generalized and normal logic programming where initially negated literals are updated. These results are discussed with respect to the understanding of negation in logic.
Reply on RC2
2021-05-27

<strong class="journal-contentHeaderColor">Abstract.</strong> Detrital tracer thermochronology utilizes the relationship between bedrock thermochronometric ageâelevation profiles and a distribution of detrital grain ages collected from riverine, glacial, or other sediment to study spatial variations in the distribution of catchment erosion. If bedrock ages increase linearly with elevation, spatially uniform erosion is expected to yield a detrital age distribution that mimics the shape of a catchment's hypsometric curve. Alternatively, a mismatch between detrital and hypsometric distributions may indicate spatial variability of sediment production within the source area. For studies seeking to identify the pattern of sediment production, detrital samples rarely exceed 100 grains due to the time and costs related to individual measurements. With sample sizes of this order, detecting the dissimilarity between two detrital age distributions produced by different catchment erosion scenarios can be difficult at a high statistical confidence level. However, there are no established software tools to quantify the uncertainty inherent to detrital tracer thermochronology as a function of sample size and spatial pattern of sediment production. As a result, practitioners are often left wondering âhow many grains is enough to detect a certain signal?â. Here, we investigate how sample size affects the uncertainty of detrital age distributions and how such uncertainty affects the ability to infer a pattern of sediment production of the upstream area. We do this using the KolmogorovâSmirnov statistic as a metric of dissimilarity among distributions. From this, we perform statistical hypothesis testing by means of Monte Carlo sampling. These techniques are implemented in a new tool (<i>ESD_thermotrace</i>) to (i)Â consistently report the confidence level allowed by the sample size as a function of application-specific variables and given a set of user-defined hypothetical erosion scenarios, (ii)Â analyze the statistical power to discern each scenario from the uniform erosion hypothesis, and (iii)Â identify the erosion scenario that is least dissimilar to the observed detrital sample (if available). <i>ESD_thermotrace</i> is made available as a new open-source Python-based script alongside the test data. Testing between different hypothesized erosion scenarios with this tool provides thermochronologists with the minimum sample size (i.e., number of bedrock and detrital grain ages) required to answer their specific scientific question at their desired level of statistical confidence.
NLRP3 Inflammasome Assembly in Neutrophils Is Supported by PAD4 and Promotes NETosis Under Sterile Conditions
2021-05-28

Neutrophil extracellular trap formation (NETosis) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome assembly are associated with a similar spectrum of human disorders. While NETosis is known to be regulated by peptidylarginine deiminase 4 (PAD4), the role of the NLRP3 inflammasome in NETosis was not addressed. Here, we establish that under sterile conditions the cannonical NLRP3 inflammasome participates in NETosis. We show apoptosis-associated speck-like protein containing a CARD (ASC) speck assembly and caspase-1 cleavage in stimulated mouse neutrophils without LPS priming. PAD4 was needed for optimal NLRP3 inflammasome assembly by regulating NLRP3 and ASC protein levels post-transcriptionally. Genetic ablation of NLRP3 signaling resulted in impaired NET formation, because NLRP3 supported both nuclear envelope and plasma membrane rupture. Pharmacological inhibition of NLRP3 in either mouse or human neutrophils also diminished NETosis. Finally, NLRP3 deficiency resulted in a lower density of NETs in thrombi produced by a stenosis-induced mouse model of deep vein thrombosis. Altogether, our results indicate a PAD4-dependent formation of the NLRP3 inflammasome in neutrophils and implicate NLRP3 in NETosis under noninfectious conditions in vitro and in vivo .
Genetic mechanisms of HLA-I loss and immune escape in diffuse large B cell lymphoma
2021-05-28

Significance Fifty percent of diffuse large B cell lymphoma (DLBCL) evade immune-surveillance via somatic genetic lesions abrogating the expression of the class I major histocompatibility complex (MHC-I) complex on the cell surface, thus preventing the presentation of tumor neoantigens to the immune system. The results herein significantly extend these findings by showing that an additional 40% of DLBCL cases, despite expressing MHC-I, carry monoallelic HLA-I genetic alterations that limit the repertoire of neoantigens for presentation to immune cells. Both MHC-I NEG and MHC-I POS /monoallelically disrupted cases have significantly higher mutational load. Notably, homozygosis of HLA-I loci is significantly and preferentially enriched in the germline of DLBCL patients, suggesting a stepwise process by which limited neoantigen presentation is selected during DLBCL development.
Nationwide Subjective and Objective Assessments of Potential Talent Predictors in Elite Youth Soccer: An Investigation of Prognostic Validity in a Prospective Study
2021-05-28

Recent studies have provided empirical evidence on the prognostic relevance of objective performance diagnostics in the soccer talent identification and development process. However, little is known about the prognostic validity of coaches' subjective evaluations of performance. This study evaluated objective and subjective assessments within a nationwide talent development program and addressed motor, perceptual skill, and personality-related performance factors. Male players ( N = 13,869; M age = 12.59 ± 1.07 years) from the age groups U12 to U15 of the German soccer talent development program participated in this study. Participants completed an objective motor diagnostic (sprint, agility, dribbling, ball control, juggling) and were subjectively rated by their coaches (kicking skills, endurance, individual tactical skills, psychosocial skills). All nine predictors were assessed with sufficient psychometric properties (α ≥ 0.72; except dribbling and ball control: α ≥ 0.53). Players' success three seasons later was operationalized by achieving professional youth academy level or not (success rate, 9%). Independent-samples t -tests analyzed univariate mean group comparisons between future selected and non-selected players. Logistic regression models examined the multivariate prognostic validity of all assessments by predicting success with subjective (model 1), objective (model 2), and both groups of predictors (model 3). Confirming the univariate prognostic validity, future selected outperformed non-selected players regarding all predictors (each p &amp;lt; 0.001, except for agility in U15: p &amp;lt; 0.01). Tactical skills, kicking skills, and sprint were of highest predictive value ( d ≥ 0.61 in each age group). Multivariate results provided empirical evidence for the subjective (7% ≤ Nagelkerke's R 2 ≤ 11%; each p &amp;lt; 0.001) and objective (8% ≤ Nagelkerke's R 2 ≤ 13%; each p &amp;lt; 0.001) assessments' prognostic validity. However, model 3 revealed the best statistical explanatory power in each age group (0.15 ≤ Nagelkerke's R 2 ≤ 0.20; p &amp;lt; 0.001). In this combined assessment model, sprint, tactical skills, and dribbling were found to be the most predictive variables. In conclusion, this study reinforces the call for multidimensional diagnostics integrating objective and subjective assessments. Future research is needed to address the demands for longitudinal analyses of subjective ratings, the integration of biological maturation, and empirical evidence for female soccer.
Randomized Controlled Trials in Medical AI A Methodological Critique
2021-05-28

Various publications claim that medical AI systems perform as well, or better, than clinical experts.However, there have been very few controlled trials and the quality of existing studies has been calledinto question. There is growing concern that existing studies overestimate the clinical benefits of AIsystems. This has led to calls for more, and higher-quality, randomized controlled trials of medicalAI systems. While this a welcome development, AI RCTs raise novel methodological challenges thathave seen little discussion. We discuss some of the challenges arising in the context of AI RCTs andmake some suggestions for how to meet them.
KEYNOTE-641: A Phase III Study of Pembrolizumab Plus Enzalutamide for Metastatic Castration-Resistant Prostate Cancer
2021-05-28

Current treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) are noncurative, and median survival upon development of mCRPC is approximately 3 years. The novel hormonal agent enzalutamide has an established role in the mCRPC treatment paradigm, and emerging evidence suggests potential synergism with enzalutamide and the PD-1 inhibitor pembrolizumab in men with mCRPC. Here, we describe the design and rationale for the multicenter, randomized, double-blind, Phase III KEYNOTE-641 study, which will be conducted to compare the efficacy and safety of pembrolizumab plus enzalutamide with that of enzalutamide plus placebo in mCRPC. <b>Clinical trial registration:</b> NCT03834493 (ClinicalTrials.gov).
Determinants of Bird Species Literacy—Activity/Interest and Specialization Are More Important Than Socio-Demographic Variables
2021-05-28

Biodiversity is declining, and knowledge about biodiversity declines in a similar way. Previous studies have already addressed predictors of species knowledge. Here, we studied bird species knowledge related to demographics, but also to individual differences in affinity to nature, by including (i) birding specialization and (ii) bird-related activities/interest. Data were collected from July to October 2020 via an online questionnaire, containing demographic data, birding specialization, interest/activity, and images of 28 bird species native to Germany. Participants were adult students, lecturers and administrative staff of the Eberhard Karls University Tübingen. A total of 1967 questionnaires were returned in this study (35.3% male, 53.8% students, 69% had access to a garden). Mean identification score was 16.31 ± 6.38. Thus, participants were able to identify more than half of the species (total species n = 28). Men identified more species than women, garden owners had higher identification scores than non-owners, while hometown size was not significant. A distance to the next forest patch &gt;10 km was related to lower identification scores. Employees scored higher than students. Correlation between species knowledge and birding specialization was high, as was the correlation with bird interest/activity. Higher scores were found in older people. In the linear univariate model, birding specialization and bird interest were the most influential predictors of species knowledge, followed by distance to next forest patch and occupation (student vs employees). Other variables were not significant. We suggest including such measures (interest, attitude, etc.) into further studies and move forward from the urban–rural narrative to more complex analyses of living circumstances.
Application of Single-Particle ICP-MS to Determine the Mass Distribution and Number Concentrations of Environmental Nanoparticles and Colloids
2021-05-28

Analyzing the elemental compositions and size distributions of nanoparticles, colloids, and their aggregates in environmental samples represents a key task in understanding contaminant, substrate, and nutrient cycling. Single-particle ICP-MS (spICP-MS) is a high-throughput method that is capable of providing the elemental mass of thousands of particles within minutes. The challenge, however, lies in data analysis and interpretation, especially for complex environmental samples. Here we present successful applications of spICP-MS for environmental samples. We first analyzed the homoaggregation behavior of synthetic microplastic and magnetite (abiogenic and biogenic) nanoparticles. The measured distribution of aggregate mass was described as a function of the number of primary particles/aggregate (Npp). In tandem with dynamic light scattering data, differences in aggregates' compactness (primary particles per nanometer) between samples can be determined. Second, we showed how sequential elemental analysis allows evaluation of the mobility of a toxic arsenic metalloid and its inferred association with colloidal Fe(III) (oxyhydr)oxides. Finally, we investigated the composition of heterogeneous iron–carbon-rich colloidal flocs, highlighting distinct colloidal Fe and C distributions and C/Fe ratios between samples from different permafrost thawing stages. On the basis of our results, we provide guidelines for successful sample preparation and promising future spICP-MS opportunities and applications with environmental samples.
Implementation of a radial disk ionization profile in the relxill_nk model
2021-05-28

Very steep reflection emissivity profiles in the inner part of accretion\\ndisks are commonly found in the analysis of X-ray observations of black hole\\nbinaries and AGN, but there is some debate about their exact origin. While\\nsteep reflection emissivity profiles can be naturally produced by compact\\ncoronae close to black holes, the measured radial emissivity parameter can be\\nfurther increased by the radial disk ionization profile when the theoretical\\nmodel assumes a disk with constant ionization. In this paper, we implement the\\npossibility of a radial disk ionization profile in the reflection model\\nRELXILL_NK, which is a package designed to calculate reflection spectra of\\n"deformed" Kerr black holes. We analyze a NuSTAR observation of the black hole\\nbinary EXO 1846-031, which was previously found to have a very high inner\\nemissivity index. We find that the model with a radial disk ionization profile\\nimproves the fit, but the impact on the estimate of the black hole spin\\nparameter and on the constraint of the deformation parameter is modest.\\nHowever, we show that the analysis of future observations of Athena and eXTP\\nwill necessarily require models with a radial disk ionization profile to have\\naccurate constraints of the deformation parameters.\\n