Performance of commercial SARS-CoV-2 wild-type and Omicron BA.1 antibody assays compared with pseudovirus neutralization tests.

BACKGROUND: Commercially available ELISA-based antibody tests are used to approximate vaccination success against SARS-CoV-2 in at-risk patients, but it is unclear whether they correlate with neutralization of the Omicron variant. METHODS: 269 serum samples of a cohort of 44 non-immunosuppressed participants and 65 MTX-treated rheumatic patients taken before and after COVID-19 booster vaccinations were measured using COVID-19 antibody testing systems with wild-type and Omicron BA.1 antigens developed by three different manufacturers (surrogate virus neutralization test cPass, and binding antibody tests QuantiVac and SeraSpot), as well as with a pseudovirus neutralization test (pVNT). The pVNT was considered the gold standard for determining the presence and level of anti-SARS-CoV-2 antibodies. RESULTS: All three wild-type ELISAs showed excellent test performance compared with wild-type neutralization in pVNT. However, out of 56 samples without Omicron BA.1 neutralization in pVNT, 71.4% showed positive results in at least one and 28.6% in all three wild-type ELISAs at the manufacturer-defined cut-offs. Omicron ELISAs showed either decreased specificity (57.1% and 55.4% for binding ELISAs) or sensitivity (51.2% in cPass) compared to Omicron neutralization in pVNT. The proportion of any false positive results among all samples decreased from 26.5% before to 3.2% after booster vaccination, however binding antibody test specificities remained below 70%. CONCLUSIONS: We found a poorer test performance of new Omicron antibody test systems compared to wild-type tests in detecting neutralizing antibodies against the corresponding SARS-CoV-2 variants. Decisions for booster vaccination or passive immunization of at-risk patients should not be based solely on antibody test results.

Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).

PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).

Characterisation of anticancer peptides at the single-cell level.

The development of efficacious anticancer therapeutics is difficult due to the heterogeneity of the cellular response to chemotherapy. Anticancer peptides (ACPs) are promising drug candidates that have been shown to be active against a range of cancer cells. However, few ACP studies focus on tumour single-cell heterogeneities. In order to address this need, we developed a microfluidic device and an imaging procedure that enable the capture, monitoring, and analysis of several hundred single cells for the study of drug response. MCF-7 human breast adenocarcinoma cells were captured in hydrodynamic traps and isolated in individual microchambers of less than 100 pL volume. With pneumatic valves, different sets of microchambers were actuated to expose the cells to various drugs. Here, the effect of three membranolytic ACPs - melittin, aurein 1.2 and aurein 2.2 - was investigated by monitoring the efflux of calcein from single MCF-7 cells. The loss of membrane integrity was observed with two different strategies that allow either focusing on one cell for mechanistic studies or parallel analysis of hundreds of individual cells. In general, the device is applicable to the analysis of the effect of various drugs on a large number of different cell types. The platform will enable us in the future to determine the origin of heterogeneous responses on pharmacological substances like ACPs within cell populations by combining it with other on-chip analytical methods.

Selective mass enhancement close to the quantum critical point in BaFe2(As1-x P x )2.

A quantum critical point (QCP) is currently being conjectured for the BaFe2(As1-x P x )2 system at the critical value x c ≈ 0.3. In the proximity of a QCP, all thermodynamic and transport properties are expected to scale with a single characteristic energy, given by the quantum fluctuations. Such a universal behavior has not, however, been found in the superconducting upper critical field H c2. Here we report H c2 data for epitaxial thin films extracted from the electrical resistance measured in very high magnetic fields up to 67 Tesla. Using a multi-band analysis we find that H c2 is sensitive to the QCP, implying a significant charge carrier effective mass enhancement at the doping-induced QCP that is essentially band-dependent. Our results point to two qualitatively different groups of electrons in BaFe2(As1-x P x )2. The first one (possibly associated to hot spots or whole Fermi sheets) has a strong mass enhancement at the QCP, and the second one is insensitive to the QCP. The observed duality could also be present in many other quantum critical systems.

Evaluation of Encephaloduroarteriosynangiosis Efficacy Using Probabilistic Independent Component Analysis Applied to Dynamic Susceptibility Contrast Perfusion MRI.

BACKGROUND AND PURPOSE: Indirect cerebral revascularization has been successfully used for treatment in Moyamoya disease and symptomatic intracranial atherosclerosis. While angiographic neovascularization has been demonstrated after surgery, measurements of local tissue perfusion are scarce and may not reflect the reported successful clinical outcomes. We investigated probabilistic independent component analysis and conventional perfusion parameters from DSC-MR imaging to measure postsurgical changes in tissue perfusion. MATERIALS AND METHODS: In this prospective study, 13 patients underwent unilateral indirect cerebral revascularization and DSC-MR imaging before and after surgery. Conventional perfusion parameters (relative cerebral blood volume, relative cerebral blood flow, and TTP) and probabilistic independent components that reflect the relative contributions of DSC signals consistent with arterial, capillary, and venous hemodynamics were calculated and examined for significant changes after surgery. Results were compared with postsurgical DSA studies to determine whether changes in tissue perfusion were due to postsurgical neovascularization. RESULTS: Before surgery, tissue within the affected hemisphere demonstrated a high probability for hemodynamics consistent with venous flow and a low probability for hemodynamics consistent with arterial flow, whereas the contralateral control hemisphere demonstrated the reverse. Consistent with symptomatic improvement, the probability for venous hemodynamics within the affected hemisphere decreased with time after surgery (P = .002). No other perfusion parameters demonstrated this association. Postsurgical DSA revealed an association between an increased preoperative venous probability in the symptomatic hemisphere and neovascularization after surgery. CONCLUSIONS: Probabilistic independent component analysis yielded sensitive measurements of changes in local tissue perfusion that may be associated with newly formed vasculature after indirect cerebral revascularization surgery.

Intrinsic and extrinsic pinning in NdFeAs(O,F): vortex trapping and lock-in by the layered structure.

Fe-based superconductors (FBS) present a large variety of compounds whose properties are affected to different extents by their crystal structures. Amongst them, the REFeAs(O,F) (RE1111, RE being a rare-earth element) is the family with the highest critical temperature Tc but also with a large anisotropy and Josephson vortices as demonstrated in the flux-flow regime in Sm1111 (Tc ∼ 55 K). Here we focus on the pinning properties of the lower-Tc Nd1111 in the flux-creep regime. We demonstrate that for H//c critical current density Jc at high temperatures is dominated by point-defect pinning centres, whereas at low temperatures surface pinning by planar defects parallel to the c-axis and vortex shearing prevail. When the field approaches the ab-planes, two different regimes are observed at low temperatures as a consequence of the transition between 3D Abrikosov and 2D Josephson vortices: one is determined by the formation of a vortex-staircase structure and one by lock-in of vortices parallel to the layers. This is the first study on FBS showing this behaviour in the full temperature, field, and angular range and demonstrating that, despite the lower Tc and anisotropy of Nd1111 with respect to Sm1111, this compound is substantially affected by intrinsic pinning generating a strong ab-peak in Jc.

Single cells in confined volumes: microchambers and microdroplets.

Microfluidic devices capable of manipulating and guiding small fluid volumes open new methodical approaches in the fields of biology, pharmacy, and medicine. They have already proven their extraordinary value for cell analysis. The emergence of microfluidic platforms has paved the way to novel analytical strategies for the positioning, treatment and observation of living cells, for the creation of chemically defined liquid environments, and for tailoring biomechanical or physical conditions in small volumes. In this article, we particularly focus on two complementary approaches: (i) the isolation of cells in small chambers defined by microchannels and integrated valves and (ii) the encapsulation of cells in microdroplets. We review the advantages and limitations of both approaches and discuss their potential for single-cell analysis and related fields. Our intention is also to give a recommendation on which platform is most appropriate for a new question, i.e., a guideline to choose the most suitable platform.

Probing transport mechanisms of BaFe2As2 superconducting films and grain boundary junctions by noise spectroscopy.

An important step forward for the understanding of high-temperature superconductivity has been the discovery of iron-based superconductors. Among these compounds, iron pnictides could be used for high-field magnet applications, resulting more advantageous over conventional superconductors, due to a high upper critical field as well as its low anisotropy at low temperatures. However, the principal obstacle in fabricating high quality superconducting wires and tapes is given by grain boundaries. In order to study these effects, the dc transport and voltage-noise properties of Co-doped BaFe2As2 superconducting films with artificial grain boundary junctions have been investigated. A specific procedure allows the separation of the film noise from that of the junction. While the former shows a standard 1/f behaviour, the latter is characterized by an unconventional temperature-dependent multi-Lorentzian voltage-spectral density. Moreover, below the film superconducting critical temperature, a peculiar noise spectrum is found for the grain boundary junction. Possible theoretical interpretation of these phenomena is proposed.

Strain induced superconductivity in the parent compound BaFe2As2.

The discovery of superconductivity with a transition temperature, Tc, up to 65 K in single-layer FeSe (bulk Tc=8 K) films grown on SrTiO3 substrates has attracted special attention to Fe-based thin films. The high Tc is a consequence of the combined effect of electron transfer from the oxygen-vacant substrate to the FeSe thin film and lattice tensile strain. Here we demonstrate the realization of superconductivity in the parent compound BaFe2As2 (no bulk Tc) just by tensile lattice strain without charge doping. We investigate the interplay between strain and superconductivity in epitaxial BaFe2As2 thin films on Fe-buffered MgAl2O4 single crystalline substrates. The strong interfacial bonding between Fe and the FeAs sublattice increases the Fe-Fe distance due to the lattice misfit, which leads to a suppression of the antiferromagnetic spin density wave and induces superconductivity with bulk Tc≈10 K. These results highlight the role of structural changes in controlling the phase diagram of Fe-based superconductors.

ALE meta-analysis on facial judgments of trustworthiness and attractiveness.

Faces convey a multitude of information in social interaction, among which are trustworthiness and attractiveness. Humans process and evaluate these two dimensions very quickly due to their great adaptive importance. Trustworthiness evaluation is crucial for modulating behavior toward strangers; attractiveness evaluation is a crucial factor for mate selection, possibly providing cues for reproductive success. As both dimensions rapidly guide social behavior, this study tests the hypothesis that both judgments may be subserved by overlapping brain networks. To this end, we conducted an activation likelihood estimation meta-analysis on 16 functional magnetic resonance imaging studies pertaining to facial judgments of trustworthiness and attractiveness. Throughout combined, individual, and conjunction analyses on those two facial judgments, we observed consistent maxima in the amygdala which corroborates our initial hypothesis. This finding supports the contemporary paradigm shift extending the amygdala's role from dominantly processing negative emotional stimuli to processing socially relevant ones. We speculate that the amygdala filters sensory information with evolutionarily conserved relevance. Our data suggest that such a role includes not only "fight-or-flight" decisions but also social behaviors with longer term pay-off schedules, e.g., trustworthiness and attractiveness evaluation.

[Meta-analyses in clinical brain research]. / Metaanalysen in der klinischen Hirnforschung.

Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have brought about an immense increase in findings on the localization of motor, cognitive, and affective processes in the human brain. However, considerable discrepancy still exists between the multitude of available studies and the limited validity of the individual experiments. Quantitative, coordinate-based meta-analyses are suited to objectively integrate these numerous findings as completely as possible. There are a number of different methods for coordinate-based voxel-wise meta-analyses, but the technique of"activation likelihood estimation" (ALE) has largely prevailed. This contribution describes the principles, methods, and statistical analysis of ALE meta-analyses and their potential for basic research in neuroscience and clinical brain research.

Bilayer microfluidic chip for diffusion-controlled activation of yeast species.

A bilayer microfluidic chip is used, in which multiple laminar streams are generated to define local microenvironments. The bilayer architecture of the microchip separates cell handling and positioning from cell activation by soluble chemicals. Cell activation is diffusion controlled through a porous membrane. By employing time-lapse fluorescence microscopy, gene expression of the enhanced green fluorescent protein (eGFP) in Saccharomyces cerevisiae is studied under various conditions. We demonstrate that the yeast cells remain viable in the microchip for at least 17 h, and that gene expression can be initiated by the supply of the inducer galactose at a spatial precision of a few micrometers.