julilili42/papers huggingface dataset:
Biallelic loss of EMC10 leads to mild to severe intellectual disability
2022-06-09

Abstract The endoplasmic reticulum membrane protein complex subunit 10 (EMC10) is a highly conserved protein responsible for the post‐translational insertion of tail‐anchored membrane proteins into the endoplasmic reticulum in a defined topology. Two biallelic variants in EMC10 have previously been associated with a neurodevelopmental disorder. Utilizing exome sequencing and international data sharing we have identified 10 affected individuals from six independent families with five new biallelic loss‐of‐function and one previously reported recurrent EMC10 variants. This report expands the molecular and clinical spectrum of EMC10 deficiency, provides a comprehensive dysmorphological assessment and highlights an overlap between the clinical features of EMC10 ‐and EMC1 ‐related disease.
Monitoring of cerebrovascular pressure reactivity in children may predict neurologic outcome after hypoxic-ischemic brain injury
2022-06-09

Abstract Objectives Impaired cerebral blood flow is a first-line reason of ischemic-hypoxic brain injury in children. The principal goal of intensive care management is to detect and prevent further cerebral blood flow deficits. This can be achieved by actively managing cerebral perfusion pressure (CPP) using input from cerebrovascular autoregulation (CAR). The main objective of the current study was to investigate CAR after cardiac arrest in children. Methods Nineteen consecutive children younger than 18 years after cardiopulmonary resuscitation, in whom intracranial pressure (ICP) was continuously measured, were included. Blood pressure and ICP were continuously monitored via ICM + software and actively managed using the pressure reactivity index (PRx) to achieve and maintain an optimal CPP. Outcome was scored using the extended Glasgow outcome scale (eGOS) at discharge and 6 months. Results Eight children died in hospital. At 6 months, further 4 children had an unfavorable (eGOS1–4) and 7 a favorable (eGOS5–8) outcome. Over the entire monitoring period, we found an elevated ICP (24.5 vs 7.4 mmHg), a lower CPP (50.3 vs 66.2 mmHg) and a higher PRx (0.24 vs − 0.01), indicating impaired CAR, in patients with unfavorable outcome. The dose of impaired autoregulation was significantly higher in unfavorable outcome (54.6 vs 29.3%). Analyzing only the first 72 h after cardiac arrest, ICP ≥ 10 mmHg and PRx &gt; 0.2 correlated to unfavorable outcome. Conclusions Significant doses of impaired CAR within 72 h after resuscitation are associated with unfavorable outcome. The inability to restore autoregulation despite active attempts to do so as well as an elevated ICP may serve as a bad prognostic sign indicating a severe initial hypoxic-ischemic brain injury.
Why Is There a Red Line? A High School Experiment to Model the Role of Gold Nanoparticles in Lateral Flow Assays for COVID-19
2022-06-09

Lateral flow assays play a key role in mass testing for COVID-19, for example, in schools. The red color of the detection lines is caused by gold nanoparticles that are conjugated to antibodies. Hence, these tests present a very topical learning opportunity in the emerging field of nanoscience. To highlight the role of gold nanoparticles, a low-cost model of a lateral flow test was developed and used in high school. First, peptide-conjugated gold or silver nanoparticles are synthesized. During the reaction, color changes occur that can be explained by the increasing nanoparticle size. The product solution is then used for the assembly of a model lateral flow test. All of the experiments can be performed by high school students. The modeling of this state-of-the-art analytical method can support learning in nanoscience and can provide insights into the nature of scientific models.
Room Temperature Fluorescence Blinking in MoS2 Atomic Layers by Single Photon Energy Transfer
2022-06-09

Abstract The quantum optical phenomena, such as single‐photon emission, in transition metal dichalcogenides (TMDCs) have triggered extensive research on 2D material‐based quantum optics and devices. By far, most reported quantum optical emissions in TMDCs are based on atomic defects or the local confinement of excitons. In contrast, energy transfer between two materials could also manipulate the photon emission behaviors in materials, even at the single‐photon level. Here, fluorescence blinking from MoS 2 atomic layers in quantum dot (QD)/MoS 2 hybrid heterostructure at room temperature is reported. The single‐photon nature of the QDs in heterostructures by second‐order photon correlation measurements is demonstrated. Based on the transient PL spectroscopy and PL time trajectories, the fluorescence blinking behavior in MoS 2 is attributed to the single‐photon energy transfer from QD to MoS 2 . This work could open the possibility to achieve correlated quantum emitters in TMDCs at room temperature.
Proteolytic Activity against the Distal Polybasic Tract of the GammaSubunit of the Epithelial Sodium Channel ENaC in Nephrotic Urine
2022-06-09

Background: Experimental nephrotic syndrome in mice leads to proteolytic activation of the epithelial sodium channel ENaC, possibly involving the distal polybasic tract of its γ-subunit (183RKRK). Objective: We sought to determine if urine samples from both nephrotic mice and a cohort of patients with acute nephrotic syndrome contain a specific proteolytic activity against this region of γ-ENaC. Method: A peptide substrate consisting of amino acids 180-194 of murine γ-ENaC was N-terminally coupled to a fluorophore, yielding AMCA-FTGRKRKISGKIIHK. The substrate was incubated with nephrotic urine samples from mice as well as patients and with or without the serine protease inhibitor aprotinin. The digested peptides were separated on a reverse phase HPLC and detected with a fluorescence detector (350/450 nm). Peptide masses of the peaks were determined with a MALDI-TOF mass spectrometer. In addition, urinary proteolytic activity was quantitated using AMC-coupled substrates reflecting different cleavage sites within the polybasic tract. Results: No significant proteolytic activity against the substrate was found in the urine of healthy humans or mice. Incubation with urine samples of nephrotic patients (n=8) or mice subjected to three different models of experimental nephrotic syndrome (n=4 each) led to cleavage of the substrate within the polybasic tract which was prevented by the serine protease inhibitor aprotinin. The most dominant cleavage product was FTGRKR in both species which was confirmed using quantitative measurements with FTGRKR-AMC. Conclusion: Nephrotic urine from both humans and mice contains aprotinin-sensitive proteolytic activity against the distal polybasic tract of γ-ENaC, reflecting excretion of active proteases in the urine or proteasuria.
The MCP2 and the wrist plus two tendons are the most affected and responsive joints/tendons out of the US7 score in patients with rheumatoid arthritis – an observational study
2022-06-09

Abstract Background : There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions to optimize it and contribute to an international consensus. Furthermore, we aimed to evaluate the impact of disease duration on the performance of the score. Methods : RA patients were assessed at baseline and after 3 and 6 months of starting/changing DMARD therapy by the US7 score in greyscale (GS) and power Doppler (PD). The frequency of pathologic joint/tendon regions and their responsiveness to therapy were analyzed by Friedman test including the comparison of palmar vs. dorsal regions (Chi-square test). The responsiveness of different reduced scores and the amount of information retained from the original US7 score were assessed by standardized response mean/linear regression. Analyses were also performed separately for early and established RA. Results : A total of 435 patients (N=138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p≤0.003 by GS/PD). The dorsal vs. palmar side of the wrist by GS/PD (p&lt;0.001) and the palmar of the finger joints by PD (p&lt;0.001) were more frequently pathologic. The reduced US7 score (GS/PD: dorsal MCP2, dorsal wrist, EDC and ECU, only GS: palmar MCP2) showed therapy response (SRM 0.433) after 6 months and retained 76% of the full US7 score’s information. No major differences between the groups of early and established RA could be detected. Conclusions : The wrist, MCP2, EDC and ECU tendons were most frequently pathologic and responsive to therapy in both early and established RA and should therefore be included in a comprehensive score for monitoring RA patients on patient-level.
Dataset (III) related to publication: Discrepancy in interactions and conformational dynamics of pregnane X receptor (PXR) bound to an agonist and a novel competitive antagonist
2022-06-09

MD simulation data related to the publication Rashidian et al.: Discrepancy in interactions and conformational dynamics of pregnane X receptor (PXR) bound to an agonist and a novel competitive antagonist. https://doi.org/10.1016/j.csbj.2022.06.020 Individual .zip files contain raw-desmond trajectories (-out.cms files and trj-files) dataset I: systems SRL+Co, C-100 and BAY-1797 dataset I: each file contains all branched replicas and the main replica. dataset1: C_100_Replica1 contains four branched replicas and the main replica. The two of four branched replicas which stem from the middle of the main replica named: b_c_D1_r1_2285 (corresponding name in the SI data is R1_a) and b_c_D1_2285_r1_2 (corresponding name in the SI data is R1_b). dataset1: C_100_Replica2–5 , each file contains one main replica and the two branches. dataset I: system SRL+Co ;each file contains one main replica dataset I: system BAY-1797; each file contains one main replica dataset II:system SRL ; each file contains one main replica. dataset III:system C-100+Co (compound 100 in presence of SRC-1 coactivator) ; each file contains one main replica.
The Effectiveness of Metagenomic Next-Generation Sequencing in the Diagnosis of Prosthetic Joint Infection: A Systematic Review and Meta-Analysis
2022-06-10

Background A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic method is particularly important for PJI. Recently, the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting PJI has attracted much attention, while the evidence of its accuracy is quite limited. Thus, this study aimed to evaluate the accuracy of mNGS for the diagnosis of PJI. Methods We summarized published studies to identify the potential diagnostic value of mNGS for PJI patients by searching online databases using keywords such as “prosthetic joint infection”, “PJI”, and “metagenomic sequencing”. Ten of 380 studies with 955 patients in total were included. The included studies provided sufficient data for the completion of 2-by-2 tables. We calculated the sensitivity, specificity, and area under the SROC curve (AUC) to evaluate mNGS for PJI diagnosis. Results We found that the pooled diagnostic sensitivity and specificity of mNGS for PJI were 0.93 (95% CI, 0.83 to 0.97) and 0.95 (95% CI, 0.92 to 0.97), respectively. Positive and negative likelihood ratios were 18.3 (95% CI, 10.9 to 30.6) and 0.07 (95% CI, 0.03 to 0.18), respectively. The area under the curve was 0.96 (95% CI, 0.93 to 0.97). Conclusion Metagenomic next-generation sequencing displays high accuracy in the diagnosis of PJI, especially for culture-negative cases.
Trait functional diversity explains mixture effects on litter decomposition at the arid end of a climate gradient
2022-06-10

Abstract Litter decomposition is controlled by climate, litter quality and decomposer communities. Because the decomposition of specific litter types is also influenced by the properties of adjacent types, mixing litter types may result in non‐additive effects on overall decomposition rates. The strength of these effects seems to depend on the litter functional diversity. However, it is unclear which functional traits or combination of traits explain litter mixture effects and whether these depend on the range of trait values and the ecosystems involved. These uncertainties hamper our ability to predict decomposition in plant communities. We aimed at understanding whether and how functional diversity (measured as functional dispersion, FDis) influences litter decomposition, and how this influence varies among different climates and across decomposition stages. We calculated FDis based on litter traits related to nutrient concentrations or to litter recalcitrance, and tested whether these diversity measures and climatic parameters (soil moisture and temperature) explained litter mixture effects on decomposition. Additive mixture effects (i.e. decomposition of mixtures equalling the mean decomposition of the single litter types) were common in most of the evaluated climates. Non‐additive, negative effects were mainly restricted to the driest and warmest sites, and decreased with time. Non‐additive effects increased in magnitude with the mixtures' FDis, with positive effects being related to FDis in nutrient traits and negative effects being related to FDis in recalcitrance traits. Synthesis . Litter mixing did not have strong effects on decomposition rates across the studied climatic gradient overall, and the direction and intensity of the mixture effects were context dependent. The effects were stronger and more negative in the dryer ecosystems. Where effects were found, functional diversity calculated from selected groups of traits (related to nutrients or litter recalcitrance) predicted mixture effects, especially where trait ranges were broad, though much of the variation remains unexplained. We propose that functional diversity metrics based on litter traits that are mechanistically relevant, applied to diverse site‐specific litter mixtures in different climates, can help to better understand under which conditions and in which direction litter diversity affects decomposition.
Clonal evolution and TCR specificity of the human T FH cell response to Plasmodium falciparum CSP
2022-06-10

T follicular helper (T FH ) cells play a crucial role in the development of long-lived, high-quality B cell responses after infection and vaccination. However, little is known about how antigen-specific T FH cells clonally evolve in response to complex pathogens and what guides the targeting of different epitopes. Here, we assessed the cell phenotype, clonal dynamics, and T cell receptor (TCR) specificity of human circulating T FH (cT FH ) cells during successive malaria immunizations with radiation-attenuated Plasmodium falciparum ( Pf ) sporozoites. Repeated parasite exposures induced a dynamic, polyclonal cT FH response with high frequency of cells specific to a small number of epitopes in Pf circumsporozoite protein (PfCSP), the primary sporozoite surface protein and well-defined vaccine target. Human leukocyte antigen (HLA) restrictions and differences in TCR generation probability were associated with differences in the epitope targeting frequency and indicated the potential of amino acids 311 to 333 in the Th2R/T* region as a T cell supertope. But most of vaccine-induced anti–amino acid 311 to 333 TCRs, including convergent TCRs with high sequence similarity, failed to tolerate natural polymorphisms in their target peptide sequence, thus demonstrating that the T FH cell response was limited to the vaccine strain. These data suggest that the high parasite diversity in endemic areas will limit boosting of the vaccine-induced T FH cell response by natural infections. Our findings may guide the further design of PfCSP-based malaria vaccines able to induce potent T helper cell responses for broad, long-lasting antibody responses.
Untargeted Metabolomics of Streptomyces Species Isolated from Soils of Nepal
2022-06-10

Actinomycetes are natural architects of numerous secondary metabolites including antibiotics. With increased multidrug-resistant (MDR) pathogens, antibiotics that can combat such pathogens are urgently required to improve the health care system globally. The characterization of actinomycetes available in Nepal is still very much untouched which is the reason why this paper showcases the characterization of actinomycetes from Nepal based on their morphology, 16S rRNA gene sequencing, and metabolic profiling. Additionally, antimicrobial assays and liquid chromatography-high resolution mass spectrometry (LC-HRMS) of ethyl acetate extracts were performed. In this study, we employed a computational-based dereplication strategy for annotating molecules which is also time-efficient. Molecular annotation was performed through the GNPS server, the SIRIUS platform, and the available databases to predict the secondary metabolites. The sequencing of the 16S rRNA gene revealed that the isolates BN6 and BN14 are closely related to Streptomyces species. BN14 showed broad-spectrum antibacterial activity with the zone of inhibition up to 30 mm against Staphylococcus aureus (MIC: 0.3051 μg/mL and MBC: 9.7656 μg/mL) and Shigella sonnei (MIC: 0.3051 μg/mL and MBC: 4.882 μg/mL). Likewise, BN14 also displayed significant inhibition to Acinetobacter baumannii, Klebsiella pneumoniae, and Salmonella typhi. GNPS approach suggested that the extracts of BN6 and BN14 consisted of diketopiperazines ((cyclo(D-Trp-L-Pro), cyclo(L-Leu-L-4-hydroxy-Pro), cyclo(L-Phe-D-Pro), cyclo(L-Trp-L-Pro), cyclo(L-Val-L-Pro)), and polypeptide antibiotics (actinomycin D and X2). Additional chemical scaffolds such as bacterial alkaloids (bohemamine, venezueline B, and G), anthramycin-type antibiotics (abbeymycin), lipase inhibitor (ebelactone B), cytocidal (oxopropaline D), antifungal and antitumor antibiotics (reductiomycin, streptimidone, deoxynybomycin), alaremycin, fumaramidmycin, anisomycin, and others were also annotated, which were further confirmed by using the SIRIUS platform, and literature survey. Thus, the bioprospecting of natural products from Streptomyces species from Nepal could be a potential source for the discovery of clinically significant and new antimicrobial agents in the future.
Snakes on a Plan: Compiling Python Functions into Plain SQL Queries
2022-06-10

"Move your computation close to the data" is decades-old advice that is hard to follow if your code exhibits complex control flow. The runtime of such applications suffers from a continual back and forth between database-external code execution and plan-based SQL evaluation. We demonstrate the ByePy compiler which translates entire Python functions with arbitrary control flow-including deeply nested iteration-into plain recursive SQL:1999 queries. The invocation of a ByePy-compiled function enters the database engine once to execute the plan of a single query. Computation does not get much closer to the data than this. The system rewards this translation effort from Python to SQL with runtime improvements of up to an order of magnitude.
International Cooperative Research: Experiences and Insights from the Project on Confirmation Work in Europe
2022-06-10

Abstract This article describes the long-term research project on confirmation work in Europe which is carried out in ten countries, and discusses it as an example of international cooperative and comparative research in practical theology. Against the background of an increasing demand for international research in practical theology on the one hand and the far-reaching lack of respective studies which is demonstrated by an analysis of the articles published in IJPT on the other, major results and methodological questions from the project on confirmation work are presented. In a final section, the advantages as well as the challenges of international cooperative and comparative research are discussed.
Novel Three-Dimensional and Biocompatible Lift-Off Method for Selective Metallization of a Scleral Contact Lens Electrode for Biopotential Detection
2022-06-10

Presbyopia describes the eye's physiological loss of the ability to see close objects clearly. The adaptation to different viewing distances, termed accommodation, is achieved by a change in the curvature of the eye lens induced by the ciliary muscle. A possible approach to correct presbyopia could be to detect the ciliary muscle's neuromuscular signals during accommodation and transfer these signals electronically to a biomimetic, micro-optical system to provide the necessary refractive power. As a preliminary step toward such a described system, a novel three-dimensional and biocompatible lift-off method was developed. In addition, the influence of the distance between the electrically conducting surfaces of the lens on the accommodated signal amplitudes was investigated. Compared to the conventional masking methods, this process has the advantage that three-dimensional surfaces can be masked with biocompatible gelling sugar by utilizing a direct writing process with a dispensing robot. Since gelling sugar can be used at room temperature and is water-soluble, the process presented is suitable for materials that should not be exposed to organic solvents or excessively high temperatures. Apart from investigating the shrinkage behavior of the gelling sugar during the physical vapor deposition (PVD) coating process, this paper also describes the approaches used to partially coat a commercial scleral contact lens with an electrically conductive material. It was shown that gelling sugar withstands the conditions during the PVD processes and a successful lift-off was performed. To investigate the influence of the spacing between the electrically conductive regions of the contact lens on the measured signals, three simplified electrode configurations with different distances were fabricated using a 3D printer. By testing these in an experimental setup, it could be demonstrated that the distance between the conductive surfaces has a significant influence on the amplitude. Regarding the described lift-off process using gelling sugar, it was found that the dispensing flow rate has a direct influence on the line uniformity. Future work should address the influence of the viscosity of the gelling sugar as well as the diameter of the cannula. It is assumed that they are the prevailing limitations for the lateral resolution.
A variation of Hilbert’s axioms for euclidean geometry
2022-06-10

Abstract We propose a variation of Hilbert’s axioms for euclidean geometry which appears to us to be more intuitive, and which supports more directly Euclid’s original approach to the criteria for congruence of triangles.
Human single-cell TCR data from irradiated sporozoite trial
2022-06-10

&lt;p&gt;This is the MiAIRR-compliant single-cell AIRR-seq data of the study &quot;Clonal evolution and TCR specificity of the human&lt;br&gt; TFH cell response to Plasmodium falciparum CSP&quot; by Wahl &lt;em&gt;et al.,&lt;/em&gt; &lt;em&gt;Sci Immunol&lt;/em&gt; 7:eabm9644 (2022). The study defines the clonal evolution and epitope specificity of the human cTFH cell response to Plasmodium falciparum CSP.&lt;/p&gt;