Showing papers by "University of Marburg published in 2022"

Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive older adults

Abstract: Here we compared SARS-CoV-2-specific antibody and T-cell responses between older adults (>80 years old, n = 51) and a younger control group (20-53 years old, n = 46) after receiving two doses of BNT162b2. We found that responses in older adults were generally lower, and we identified 10% low-/non-responders. After receiving a third vaccination with BNT162b2, 4 out of 5 low-/non-responders showed antibody and T-cell responses similar to those of responders after two vaccinations.

The pocketome of G-protein-coupled receptors reveals previously untargeted allosteric sites

Abstract: G-protein-coupled receptors do not only feature the orthosteric pockets, where most endogenous agonists bind, but also a multitude of other allosteric pockets that have come into the focus as potential binding sites for synthetic modulators. Here, to better characterise such pockets, we investigate 557 GPCR structures by exhaustively docking small molecular probes in silico and converting the ensemble of binding locations to pocket-defining volumes. Our analysis confirms all previously identified pockets and reveals nine previously untargeted sites. In order to test for the feasibility of functional modulation of receptors through binding of a ligand to such sites, we mutate residues in two sites, in two model receptors, the muscarinic acetylcholine receptor M3 and β2-adrenergic receptor. Moreover, we analyse the correlation of inter-residue contacts with the activation states of receptors and show that contact patterns closely correlating with activation indeed coincide with these sites.

Electronic structure and bonding in endohedral Zintl clusters

Abstract: Endohedral Zintl clusters-multi-metallic anionic molecules in which a d-block or f-block metal atom is enclosed by p-block (semi)metal atoms-are very topical in contemporary inorganic chemistry. Not only do they provide insight into the embryonic states of intermetallic compounds and show promise in catalytic applications, they also shed light on the nature of chemical bonding between metal atoms. Over the past two decades, a plethora of endohedral Zintl clusters have been synthesized, revealing a fascinating diversity of molecular architectures. Many different perspectives on the bonding in them have emerged in the literature, sometimes complementary and sometimes conflicting, and there has been no concerted effort to classify the entire family based on a small number of unifying principles. A closer look, however, reveals distinct patterns in structure and bonding that reflect the extent to which valence electrons are shared between the endohedral atom and the cluster shell. We show that there is a much more uniform relationship between the total valence electron count and the structure and bonding patterns of these clusters than previously anticipated. All of the p-block (semi)metal shells can be placed on a ladder of total valence electron count that ranges between 4n+2 (closo deltahedra), 5n (closed, three-bonded polyhedra) and 6n (crown-like structures). Although some structural isomerism can occur for a given electron count, the presence of a central metal cation imposes a preference for rather regular and approximately spherical structures which maximise electrostatic interactions between the metal and the shell. In cases where the endohedral metal has relatively accessible valence electrons (from the d or f shells), it can also contribute its valence electrons to the total electron count of the cluster shell, raising the effective electron count and often altering the structural preferences. The electronic situation in any given cluster is considered from different perspectives, some more physical and some more chemical, in a way that highlights the important point that, in the end, they explain the same situation. This article provides a unifying perspective of bonding that captures the structural diversity across this diverse family of multimetallic clusters.

Quasi-Relativistic Calculation of EPR <i>g</i> Tensors with Derivatives of the Decoupling Transformation, Gauge-Including Atomic Orbitals, and Magnetic Balance

Abstract: We present an exact two-component (X2C) ansatz for the EPR g tensor using gauge-including atomic orbitals (GIAOs) and a magnetically balanced basis set expansion. In contrast to previous X2C and four-component relativistic ansätze for the g tensor, this implementation results in a gauge-origin-invariant formalism. Furthermore, the derivatives of the relativistic decoupling matrix are incorporated to form the complete analytical derivative of the X2C Hamiltonian. To reduce the associated computational costs, we apply the diagonal local approximation to the unitary decoupling transformation (DLU). The quasi-relativistic X2C and DLU-X2C Hamiltonians accurately reproduce the results of the parent four-component relativistic theory when accounting for two-electron picture-change effects with the modified screened nuclear spin-orbit approximation in the respective one-electron integrals and integral derivatives. According to our benchmark studies, the uncontracted Dyall and segmented-contracted Karlsruhe x2c-type basis sets perform well when compared to large even-tempered basis sets. Moreover, (range-separated) hybrid density functional approximations such as LC-ωPBE and ωB97X-D are needed to match the experimental findings. The impact of the GIAOs depends on the distribution of the spin density, and their use may change the Δg shifts by 10-50% as shown for [(C5Me5)2Y(μ-S)2Mo(μ-S)2Y(C5Me5)2]-. Routine calculations of large molecules are possible with widely available and comparably low-cost hardware as demonstrated for [Pt(C6Cl5)4]- with 3003 basis functions and three spin-(1/2) La(II) and Lu(II) compounds, for which we observe good agreement with the experimental findings.

Dynamics of humoral and T-cell immunity after three BNT162b2 vaccinations in adults older than 80 years.

Abstract: A third mRNA-based booster vaccination is the currently favoured strategy to maintain protection against SARS-CoV-2 infection. Yet, significant waning of specific immunity within 6 months after two doses,1 along with a higher incidence of breakthrough infections associated with the time elapsed since the second dose,2,3 raise concerns regarding the durability of immunity also after the booster vaccination.

Early Tracheostomy Is Associated With Shorter Ventilation Time and Duration of ICU Stay in Patients With Myasthenic Crisis-A Multicenter Analysis.

Abstract: Background:Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk fac...

Regioselective Fluorination of Acenes: Tailoring of Molecular Electronic Levels and Solid‐State Properties

Abstract: Optoelectronic properties of molecular solids are important for organic electronic devices and are largely determined by the adopted molecular packing motifs. In this study, we analyzed such structure-property relationships for the partially regioselective fluorinated tetracenes 1,2,12-trifluorotetracene, 1,2,10,12-tetrafluorotetracene and 1,2,9,10,11-pentafluorotetracene that were further compared with tetracene and perfluoro-tetracene. Quantum chemical DFT calculations in combination with optical absorption spectroscopy data show that the frontier orbital energies are lowered with the degree of fluorination, while their optical gap is barely affected. However, the crystal structure changes from a herringbone packing motif of tetracene towards a planar stacking motif of the fluorinated tetracene derivatives, which is accompanied by the formation of excimers and leads to strongly red-shifted photoluminescence with larger lifetimes.

Between imide, imidyl and nitrene – an imido iron complex in two oxidation states

Abstract: A pair of trigonal imido iron complexes ([Fe(NMes)L 2 ] 0,− ) in two oxidation states is reported. The anionic complex K{crypt.222}[Fe(NMes)L 2 ] is best described as an iron( ii ) imide.

Climate warming changes synchrony of plants and pollinators

Abstract: Climate warming changes the phenology of many species. When interacting organisms respond differently, climate change may disrupt their interactions and affect the stability of ecosystems. Here, we used global biodiversity facility occurrence records to examine phenology trends in plants and their associated insect pollinators in Germany since the 1980s. We found strong phenological advances in plants but differences in the extent of shifts among pollinator groups. The temporal trends in plant and insect phenologies were generally associated with interannual temperature variation and thus probably driven by climate change. When examining the synchrony of species-level plant–pollinator interactions, their temporal trends differed among pollinator groups. Overall, plant–pollinator interactions become more synchronized, mainly because the phenology of plants, which historically lagged behind that of the pollinators, responded more strongly to climate change. However, if the observed trends continue, many interactions may become more asynchronous again in the future. Our study suggests that climate change affects the phenologies of both plants and insects and that it also influences the synchrony of plant–pollinator interactions.

Corporate profit shifting and the role of tax havens: Evidence from German country-by-country reporting data

Abstract: This paper is the first to use information from individual country-by-country (CbC) reports to assess the extent of profit shifting by multinational enterprises. Unlike other data often used to evaluate the extent of profit shifting and tax avoidance, CbC reports provide a complete coverage of the global distribution of profits and indicators of economic activity for multinationals exceeding a certain revenue threshold. We show that 82% of the German multinationals subject to CbC reporting have tax haven subsidiaries and that these subsidiaries are notably more profitable than those in non-havens. However, only 9% of the global profits of German multinationals are reported in tax havens. Results from regression analysis suggest that approximately 40% of the profits reported in tax havens are a result of tax-induced profit shifting. The associated annual tax base loss for Germany amounts to EUR 5.4 billion, corresponding to 4.3% of the profits reported by these firms in Germany. This implies a tax revenue loss of EUR 1.6 billion per year.

Trust in Artificial Intelligence: Comparing Trust Processes Between Human and Automated Trustees in Light of Unfair Bias

Abstract: Abstract Automated systems based on artificial intelligence (AI) increasingly support decisions with ethical implications where decision makers need to trust these systems. However, insights regarding trust in automated systems predominantly stem from contexts where the main driver of trust is that systems produce accurate outputs (e.g., alarm systems for monitoring tasks). It remains unclear whether what we know about trust in automated systems translates to application contexts where ethical considerations (e.g., fairness) are crucial in trust development. In personnel selection, as a sample context where ethical considerations are important, we investigate trust processes in light of a trust violation relating to unfair bias and a trust repair intervention. Specifically, participants evaluated preselection outcomes (i.e., sets of preselected applicants) by either a human or an automated system across twelve selection tasks. We additionally varied information regarding imperfection of the human and automated system. In task rounds five through eight, the preselected applicants were predominantly male, thus constituting a trust violation due to potential unfair bias. Before task round nine, participants received an excuse for the biased preselection (i.e., a trust repair intervention). The results of the online study showed that participants have initially less trust in automated systems. Furthermore, the trust violation and the trust repair intervention had weaker effects for the automated system. Those effects were partly stronger when highlighting system imperfection. We conclude that insights from classical areas of automation only partially translate to the many emerging application contexts of such systems where ethical considerations are central to trust processes.

Post-COVID-19 conditions in children and adolescents diagnosed with COVID-19

Abstract: This study aimed to investigate the prevalence of and the factors associated with post-COVID-2019 condition in COVID-19 children and adolescents in Germany.The present retrospective cohort study used data from the Disease Analyzer database (IQVIA), and included patients aged <18 years who were diagnosed with COVID-19 in one of 524 general and 81 pediatric practices in Germany between October 2020 and August 2021 (index date: first COVID-19 diagnosis). Post-COVID-19 condition was assessed between the index date and November 2021. Covariates included age, sex, type of practice, and chronic conditions documented in at least 1% of the population.There were 6568 children and adolescents included in this study (mean [SD] age 10.1 [4.9] years; 49.2% girls). The prevalence of post-COVID-19 condition was 1.7% in the population. Patients aged 13-17 years were more likely to be diagnosed with post-COVID-19 condition compared with those being aged ≤5 years (RR = 3.14). Anxiety disorders (RR = 2.53), somatoform disorders (RR = 2.11), and allergic rhinitis (RR = 2.02) were also significantly associated with post-COVID-19 condition.Post-COVID-19 condition was rare in COVID-19 children and adolescents in Germany. Data from other settings are warranted to confirm these findings.The prevalence of post-COVID-19 condition was 1.7% in this population of children and adolescents. Older children and adolescents were more likely to be diagnosed with post-COVID-19 condition than their younger counterparts. Anxiety disorders, somatoform disorders, and allergic rhinitis were significantly associated with post-COVID-19 condition. More data from other settings and countries are warranted to corroborate or refute these findings.

Influence of polymer matrix on the induction heating behavior of CFRPC laminates

Abstract: Within this study, the influence on the induction heating rate of different matrix polymer systems in combination with different reinforcing fabrics made of carbon fibers (CF) was experimentally investigated for a frequency of 480 kHz. Additionally, an electrical model representing CF-CF junctions in non-crimped fabrics, as well as roving-roving junctions in woven fabrics, was developed. The dielectric properties of the polymer matrix have no significant influence on the induction heating behavior of CFRPC compared to other laminate parameters. Compared to the heat dissipated due to the contact resistance m, the heat dissipated at one cross-junction due to dielectric losses is up to twelve decades lower. The dominant heating mechanism for induction heating of CFRPC laminates crucially depends on the magnitude of contact resistivity at the cross-junction. Below a contact resistivity of 10−5 Ω*m2 the losses due to Joule heating and beyond 10−5 Ω*m2 the losses due to contact resistances dominate.

Mild Cognitive Disorder in Post-COVID-19 Syndrome: A Retrospective Cohort Study of 67,000 Primary Care Post-COVID Patients

Abstract: Little is known about the impact of COVID-19 on mild cognitive disorder.The aim of this retrospective cohort study was to investigate whether COVID-19 diagnosis is associated with subsequent mild cognitive disorder (MCD) compared to acute upper respiratory infections (AURI).This retrospective cohort study used data from the Disease Analyzer database (IQVIA) and included 67,046 patients with first-time symptomatic or asymptomatic COVID-19 diagnoses in 1,172 general practices in Germany between March 2020 and September 2021. Diagnoses were based on ICD-10 codes. Patients diagnosed with AURI were matched to 67,046 patients with COVID-19 using propensity scores based on sex, age, index month, and comorbidities. The index date was the diagnosis date for either COVID-19 or AURI. Associations between the COVID-19 and MCD were studied using conditional Poisson regression models.The incidence of MCD was 7.6 cases per 1,000 person-years in the COVID-19 group and 5.1 cases per 1,000 person-years in the AURI group (IRR = 1.49, 95% CI = 1.22-1.82). The incidence rate ratio decreased strongly with increasing age from 10.08 (95% CI = 4.00-24.42) in the age group≤50 to 1.03 (95% CI = 0.81-1.31) in the age group > 70. In addition, the association between COVID-19 and MCD was significant in women (IRR: 1.70, 95% CI: 1.34-2.16) but not in men (IRR: 1.08, 95% CI: 0.75-1.56).The incidence of MCD was low but significantly higher in COVID-19 than in AURI patients, especially among younger patients. If a cognitive disorder is suspected, referral to a specialist is recommended.

Heroic behavior: A review of the literature on high-stakes altruism in the wild

Abstract: This review compiles and contextualizes the available empirical literature on natural occurrences of high-stakes altruism among nonrelatives, i.e., behaviors often called 'heroic'. Four domains are covered: exceptional bravery and self-sacrifice in war, heroism in civilian life, undirected organ donations, and rescues of persecuted persons during mass violence and genocides. The diversity of strategies used to identify instances of heroic behavior and the multiplicity of data collection methods employed in this relatively sparse literature currently preclude a systematic comparison of results. Therefore, the aim of this overview is to provide an exhaustive point of entry to a fascinating field of research with much untapped potential for testing theories about prosocial behavior.

Critically high metal ion levels found in metal-on-metal modular hinged knee arthroplasty

Abstract: This study compared the cobalt and chromium serum ion concentration of patients treated with two different metal-on-metal (MoM) hinged total knee arthroplasty (TKA) systems, as well as a titanium nitride (TiN)-coated variant.A total of 63 patients (65 implants) were treated using either a MoM-coated (n = 29) or TiN-coated (n = 7) hinged TKA (GenuX mobile bearing, MUTARS; Implantcast, Germany) versus the BPKS (Brehm, Germany) hinged TKA (n = 27), in which the weight placed on the MoM hinge is diffused through a polyethylene (PE) inlay, reducing the direct load on the MoM hinge. Serum cobalt and chromium ion concentrations were assessed after minimum follow-up of 12 months, as well as functional outcome and quality of life.No differences in mean age (69 years, 40 to 86), mean age adapted Charlson Comorbidity Index (3.1 (SD 1.4)), mean BMI (29.2 kg/m2 (SD 5.8)), or number of other implants were observed between groups. Significant improvements in outcome scores and pain levels were achieved for all groups, and there was no difference in quality of life (12-Item Short-Form Health Survey questionnaire (SF-12)). Mean cobalt and chromium ion levels were significantly higher for the GenuX versus the BPKS hinged TKA (GenuX vs BPKS: cobalt: 16.3 vs 9.4 µg/l; chromium: 9.5 vs 5.2 µg/l). The TiN-coated implants did not appear to confer improvement in the metal ion levels. Metal ion concentrations above 7 µg/l were detected in 81%(29/36) of GenuX patients versus 41% (11/27) in the BPKS group. No GenuX patients had normal levels under 2 µg/l, versus 22% of BPKS patients. No significant reduction in outcome scores was observed regardless of the metal ion levels, whereas higher work-related activity was correlated with higher chromium concentrations.Hinged TKA, using MoM hinges, resulted in critically high cobalt and chromium ion concentrations. The BPKS hinged TKA showed significantly lower metal ion concentrations compared with the GenuX TKA. No benefits were observed using TiN coating. The different weightbearing mechanics might influence the wear of the component materials. Higher workloads and physical activity could influence chromium levels. Cite this article: Bone Joint J 2022;104-B(3):376-385.

Heroic behavior: A review of the literature on high-stakes altruism in the wild.

Abstract: This review compiles and contextualizes the available empirical literature on natural occurrences of high-stakes altruism among nonrelatives, i.e., behaviors often called ‘heroic’. Four domains are covered: exceptional bravery and self-sacrifice in war, heroism in civilian life, undirected organ donations, and rescues of persecuted persons during mass violence and genocides. The diversity of strategies used to identify instances of heroic behavior and the multiplicity of data collection methods employed in this relatively sparse literature currently preclude a systematic comparison of results. Therefore, the aim of this overview is to provide an exhaustive point of entry to a fascinating field of research with much untapped potential for testing theories about prosocial behavior.

Negative affect related traits and the chasm between self-report and neuroscience

Abstract: Fifty years of neurobiological research on negative affect related traits (NART) has, if anything, only found relatively few and small replicable effects. Here, we outline ten issues potentially contributing to a conceptual chasm between NART and neurobiological measures relating to (A) measurements of individual differences in neurobiological variables, (B) conceptualizations of trait variables, and (C) potential relationships between trait and neurobiological variables. We believe that these issues may transfer to neurobiological research on other traits and that addressing them in future work may contribute to replicable results and valid interpretations. The issues raised also suggest the need for a comprehensive neurobiological theory of NART and for well-designed theory-based studies that may narrow the chasm between traits and neurobiological markers.

High-spin carbonyl complexes of iron(<scp>i</scp>) and cobalt(<scp>i</scp>)

Abstract: Metal carbonyl complexes are almost exclusively found in a low-spin state due to the strong-field nature of the CO ligand. Here the characterisation of highly labile three-coordinate metal(I) monocarbonyl complexes of iron and cobalt is presented. Experimental and quantum chemical examinations reveal their high-spin configuration.

Post‐neoadjuvant assessment of tumour budding according to <scp>ITBCC</scp> subgroups delivers stage‐ and <scp>regression‐grade</scp> independent prognostic information in intestinal‐type gastric adenocarcinoma

Abstract: Tumour budding (TB) has been associated with adverse clinicopathological factors and poor survival in a plethora of therapy-naïve carcinoma entities including gastric adenocarcinoma (GC). As conventional histopathological grading is usually omitted in the post-neoadjuvant setting of GC, our study aimed to investigate the prognostic impact of TB in GCs resected after neoadjuvant therapy. We evaluated TB according to the criteria from the International Tumour Budding Consensus Conference (ITBCC) in 167 post-neoadjuvant resections of intestinal-type GC and correlated the results with overall survival (OS) and clinicopathological parameters. GCs were categorised into Bd1 (0-4 buds, low TB), Bd2 (5-9 buds, intermediate TB), and Bd3 (≥10 buds, high TB). Carcinomas with intermediate and high TB were significantly enriched in higher ypTNM stages and strongly associated with reduced 5-year OS in univariable analyses (p < 0.001). In multivariable analyses including sex, age, resection status, UICC stage, and tumour regression grading, TB remained a stage-independent predictor of survival (p < 0.001, hazard ratio Bd2: 2.60, Bd3: 4.74). The assessment of TB according to the ITBCC criteria provides valuable prognostic information in the post-neoadjuvant setting of intestinal-type GC and may be a considerable substitute for the conventional grading system in GCs after neoadjuvant therapy.

The antioxidant Rutin counteracts the pathological impact of α-synuclein on the enteric nervous system in vitro.

Abstract: Motoric disturbances in Parkinson's disease (PD) derive from the loss of dopaminergic neurons in the substantia nigra. Intestinal dysfunctions often appear long before manifestation of neuronal symptoms, suggesting a strong correlation between gut and brain in PD. Oxidative stress is a key player in neurodegeneration causing neuronal cell death. Using natural antioxidative flavonoids like Rutin, might provide intervening strategies to improve PD pathogenesis. To explore the potential effects of micro (mRutin) compared to nano Rutin (nRutin) upon the brain and the gut during PD, its neuroprotective effects were assessed using an in vitro PD model. Our results demonstrated that Rutin inhibited the neurotoxicity induced by A53T α-synuclein (Syn) administration by decreasing oxidized lipids and increasing cell viability in both, mesencephalic and enteric cells. For enteric cells, neurite outgrowth, number of synaptic vesicles, and tyrosine hydroxylase positive cells were significantly reduced when treated with Syn. This could be reversed by the addition of Rutin. nRutin revealed a more pronounced result in all experiments. In conclusion, our study shows that Rutin, especially the nanocrystals, are promising natural compounds to protect neurons from cell death and oxidative stress during PD. Early intake of Rutin may provide a realizable option to prevent or slow PD pathogenesis.