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We present an IR-PD study of tantalum cluster adsorbate complexes [Tan(N2)m]+, abbreviated (n,m), n = 5–8. We utilize infrared spectroscopy of isolated and size selected clusters as prepared and characterized by a cryogenic tandem ion trap setup, and we augment our experiments with quantum chemical simulations at the level of density functional theory. The cluster adsorbate complexes (n,m) reveal vibrational bands above 2000 cm−1, which indicate end-on coordinated μ1-N2 oscillators, and bands below 2000 cm−1, which indicate side-on μ2-κN:κN,N coordinated ones. We observe a general increase in spectral complexity and an inhomogeneous broadening, mainly towards the red, at certain points of N2 loading m, which originates from an increasingly higher amount of double and triple N2 coordination at Ta sites, eventually at all of them. Other than the small tantalum clusters Tan+, n = 2–4, the IR-PD spectra of the initial N2 adsorbate species (n,1), n = 5–8, provide strong evidence for a lack of spontaneous N2 cleavage. Spontaneous N2 cleavage by Tan+, n = 5–8, seems suppressed. Therefore, the ability of a small Ta cluster to cleave dinitrogen disappears with one more tantalum core atom. The study of stepwise N2 adsorption on size selected Tan+, n = 5–8 clusters revealed adsorption limits m(max) of [Tan(N2)m]+ that are independent of cluster size within this size range. Cryo-adsorption kinetics at 26 K allowed for kinetic fits to consecutive N2 adsorption steps, and the fits revealed significant N2 desorption rates upon higher N2 loads, and the cluster adsorbate complexes eventually reached equilibrium. Some enhanced N2 desorption rates point towards likely adsorbate shell reorganization, and there is also some evidence for the coexistence of isomeric cluster adsorbate complexes. [ABSTRACT FROM AUTHOR]

We investigate small tantalum clusters Tan+, n = 2–4, for their capability to cleave N2 adsorption spontaneously. We utilize infrared photon dissociation (IR-PD) spectroscopy of isolated and size selected clusters under cryogenic conditions within a buffer gas filled ion trap, and we augment our experiments by quantum chemical simulations (at DFT level). All Tan+ clusters, n = 2–4, seem to cleave N2 efficiently. We confirm and extend a previous study under ambient conditions on Ta2+ cluster [Geng et al., Proc. Natl. Acad. Sci. U. S. A. 115, 11680–11687 (2018)]. Our cryo studies and the concomitant DFT simulations of the tantalum trimer Ta3+ suggest cleavage of the first and activation of the second and third N2 molecule across surmountable barriers and along much-involved multidimensional reaction paths. We unravel the underlying reaction processes and the intermediates involved. The study of the N2 adsorbate complexes of Ta4+ presented here extends our earlier study and previously published spectra from (4,m), m = 1–5 [Fries et al., Phys. Chem. Chem. Phys. 23(19), 11345–11354 (2021)], up to m = 12. We confirm the priory published double activation and nitride formation, succeeded by single side-on N2 coordination. Significant red shifts of IR-PD bands from these side-on coordinated μ2-κN:κN,N N2 ligands correlate with the degree of tilting towards the second coordinating Ta center. All subsequently attaching N2 adsorbates onto Ta4+ coordinate in an end-on fashion, and we find clear evidence for co-existence of end-on coordination isomers. The study of stepwise N2 adsorption revealed adsorption limits m(max) of [Tan(N2)m]+ which increase with n, and kinetic fits revealed significant N2 desorption rates upon higher N2 loads. The enhanced absolute rate constants of the very first adsorbate steps kabs(n,0) of the small Ta3+ and Ta4+ clusters independently suggest dissociative N2 adsorption and likely N2 cleavage into Ta nitrides. [ABSTRACT FROM AUTHOR]

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Interactions at high temperatures between thin films and the Si substrate limit materials discovery using combinatorial processing platforms (CPPs). To overcome this, a diffusion and reaction barrier, SiO2, by thermal oxidation of Si tips is developed. The application of this diffusion barrier in CPPs for atomic‐scale investigations of new materials in atom probe tomography is reported. Thermal SiO2 layers (20 and 50 nm thick) are examined as barriers to separate coatings from Si tips. Pt is chosen as it easily forms silicides. CPPs are sequentially annealed in vacuum at 400 °C for 10 h, 600 °C for 2 h, and 800 °C for 2 h. The thermal SiO2 diffusion barrier remains stable and prevents intermixing at least up to 800 °C. Moreover, it provides improved film adhesion as dewetting of Pt on the oxide surface occurred at 800 °C instead of 600 °C without a thermal diffusion barrier. A comprehensive structural and chemical analysis of the Pt film, the thermal SiO2 layer, and their interfaces is performed using scanning and transmission electron microscopy, and atom probe tomography. As a result, the thermal SiO2 forms a stable barrier, even at the lowest thickness of 20 nm, avoiding the formation of Pt silicides, even at 800 °C. [ABSTRACT FROM AUTHOR]

This study aimed to assess the suitability of fermented food interventions to replenish damaged gut microbiota. Metagenomic assessment of published sequencing data found that fermented food interventions led to a significant increase in the gut antibiotic resistome in healthy human subjects. Antibiotic resistome and viable antibiotic-resistant (AR) bacteria were further highly prevalent in retail kimchi and artisan cheeses by metagenomic and culture analyses. Representative AR pathogens of importance in nosocomial infections, such as Klebsiella pneumoniae, Serratia marcescens, and vancomycin-resistant Enterococcus (VRE), as well as commensals and lactic acid bacteria, were characterized; some exhibited an extremely high minimum inhibitory concentration (MIC) against antibiotics of clinical significance. Exposing fermented food microbiota to representative antibiotics further led to a boost of the corresponding antibiotic and multidrug-resistance gene pools, as well as disturbed microbiota, including the rise of previously undetectable pathogens. These results revealed an underestimated public health risk associated with fermented food intervention at the current stage, particularly for susceptible populations with compromised gut integrity and immune functions seeking gut microbiota rescue. The findings call for productive intervention of foodborne AR via technology innovation and strategic movements to mitigate unnecessary, massive damages to the host gut microbiota due to orally administered or biliary excreted antibiotics. [ABSTRACT FROM AUTHOR]

Introduction: Females of the Northern house mosquito, Culex pipiens, enter an overwintering dormancy, or diapause, in response to short day lengths and low environmental temperatures that is characterized by small egg follicles and high starvation resistance. During diapause, Culex pipiens Major Royal Jelly Protein 1 ortholog (CpMRJP1) is upregulated in females of Cx. pipiens. This protein is highly abundant in royal jelly, a substance produced by honey bees (Apis mellifera), that is fed to future queens throughout larval development and induces the queen phenotype (e.g., high reproductive activity and longer lifespan). However, the role of CpMRJP1 in Cx. pipiens is unknown. Methods: We first conducted a phylogenetic analysis to determine how the sequence of CpMRJP1 compares with other species. We then investigated how supplementing the diets of both diapausing and nondiapausing females of Cx. pipiens with royal jelly affects egg follicle length, fat content, protein content, starvation resistance, and metabolic profile. Results: We found that feeding royal jelly to females reared in long-day, diapause-averting conditions significantly reduced the egg follicle lengths and switched their metabolic profiles to be similar to diapausing females. In contrast, feeding royal jelly to females reared in short-day, diapause-inducing conditions significantly reduced lifespan and switched their metabolic profile to be similar nondiapausing mosquitoes. Moreover, RNAi directed against CpMRJPI significantly increased egg follicle length of short-day reared females, suggesting that these females averted diapause. Discussion: Taken together, our data show that consuming royal jelly reverses several key seasonal phenotypes of Cx. pipiens and that these responses are likely mediated in part by CpMRJP1. [ABSTRACT FROM AUTHOR]

Background: With artificial intelligence (AI) on the rise, it remains unclear if AI is able to professionally evaluate medical research and give scientifically valid recommendations. Aim: This study aimed to assess the accuracy of ChatGPT's responses to ten key questions on brain abscess diagnostics and treatment in comparison to the guideline recently published by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). Methods: All ten PECO (Population, Exposure, Comparator, Outcome) questions which had been developed during the guideline process were presented directly to ChatGPT. Next, ChatGPT was additionally fed with data from studies selected for each PECO question by the ESCMID committee. AI's responses were subsequently compared with the recommendations of the ESCMID guideline. Results: For 17 out of 20 challenges, ChatGPT was able to give recommendations on the management of patients with brain abscess, including grade of evidence and strength of recommendation. Without data prompting, 70% of questions were answered very similar to the guideline recommendation. In the answers that differed from the guideline recommendations, no patient hazard was present. Data input slightly improved the clarity of ChatGPT's recommendations, but, however, led to less correct answers including two recommendations that directly contradicted the guideline, being associated with the possibility of a hazard to the patient. Conclusion: ChatGPT seems to be able to rapidly gather information on brain abscesses and give recommendations on key questions about their management in most cases. Nevertheless, single responses could possibly harm the patients. Thus, the expertise of an expert committee remains inevitable. [ABSTRACT FROM AUTHOR]

Purpose: There is an overlap in the cerebrospinal fluid (CSF) characteristics of patients presenting with different etiologies of CSF pleocytosis. Here, we characterized patients with CSF pleocytosis treated in a large hospital. Methods: A retrospective cohort study of 1150 patients with an elevated CSF leukocyte count > 5 cells/µl treated at a university hospital in Germany from January 2015 to December 2017 was performed. Information on clinical presentation, laboratory parameters, diagnosis and outcome was collected. Clinical and laboratory features were tested for their potential to differentiate between bacterial meningitis (BM) and other causes of CSF pleocytosis. Results: The most common etiologies of CSF pleocytosis were CNS infections (34%: 20% with detected pathogen, 14% without), autoimmune (21%) and neoplastic diseases (16%). CSF cell count was higher in CNS infections with detected pathogen (median 82 cells/µl) compared to autoimmune (11 cells/µl, p = 0.001), neoplastic diseases (19 cells/µl, p = 0.01) and other causes (11 cells/µl, p < 0.001). The CHANCE score was developed to differentiate BM from other causes of CSF pleocytosis: Multivariate regression revealed that CSF cell count > 100 cells/µl, CSF protein > 100 mg/dl, CRP > 5 mg/dl, elevated white blood cell count, abnormal mental status and nuchal rigidity are important indicators. The CHANCE score identified patients with BM with high sensitivity (92.1%) and specificity (90.9%) (derivation cohort: AUC: 0.955, validation cohort: AUC: 0.956). Conclusion: Overall, the most common causes for CSF pleocytosis include infectious, neoplastic or autoimmune CNS diseases in ~ 70% of patients. The CHANCE score could be of help to identify patients with high likelihood of BM and support clinical decision making. [ABSTRACT FROM AUTHOR]

Purpose: The objectives of this study were to analyse the clinical value of protein S100b (S100b) in association with clinical findings and anticoagulation therapy in predicting traumatic intracranial haemorrhage (tICH) and unfavourable outcomes in elderly individuals with low-energy falls (LEF). Methods: We conducted a retrospective study in the emergency department (ED) of the LMU University Hospital, Munich by consecutively including all patients aged ≥ 65 years presenting to the ED following a LEF between September 2014 and December 2016 and receiving an emergency cranial computed tomography (cCT) examination. Primary endpoint was the prevalence of tICH. Multivariate logistic regression models and receiver operating characteristics were used to measure the association between clinical findings, anticoagulation therapy and S100b and tICH. Results: We included 2687 patients, median age was 81 years (60.4% women). Prevalence of tICH was 6.7% (180/2687) and in-hospital mortality was 6.1% (11/180). Skull fractures were highly associated with tICH (odds ratio OR 46.3; 95% confidence interval CI 19.3–123.8, p < 0.001). Neither anticoagulation therapy nor S100b values were significantly associated with tICH (OR 1.14; 95% CI 0.71–1.86; OR 1.08; 95% CI 0.90–1.25, respectively). Sensitivity of S100b (cut-off: 0.1 ng/ml) was 91.6% (CI 95% 85.1–95.9), specificity was 17.8% (CI 95% 16–19.6), and the area under the curve value was 0.59 (95% CI 0.54 − 0.64) for predicting tICH. Conclusion: In conclusion, under real ED conditions, neither clinical findings nor protein S100b concentrations or presence of anticoagulation therapy was sufficient to decide with certainty whether a cCT scan can be bypassed in elderly patients with LEF. Further prospective validation is required. [ABSTRACT FROM AUTHOR]

We report the N2 cryo adsorption kinetics of selected gas phase mixed rhodium–iron clusters [RhiFej]+ in the range of i = 3–8 and j = 3–8 in 26 K He buffer gas by the use of a cryo tandem RF-hexapole trap–Fourier transform ion cyclotron resonance mass spectrometer. From kinetic data and fits, we extract relative rate constants for each N2 adsorption step and possible desorption steps. We find significant trends in adsorption behavior, which reveal adsorption limits, intermittent adsorption limits, and equilibrium reactions. For those steps, which are in equilibrium, we determine the Gibbs free energies. We conclude on likely ligand shell reorganization and some weakly bound N2 ligands for clusters where multiple N2 adsorbates are in equilibrium. The relative rate constants are transferred to absolute rate constants, which are slightly smaller than the collision rate constants calculated by the average dipole orientation (Langevin) theory. The calculated sticking probabilities increase, in general, with the size of the clusters and decrease with the level of N2 adsorption, in particular, when reaching an adsorption/desorption equilibrium. We receive further evidence on cluster size dependent properties, such as cluster geometries and metal atom distributions within the clusters through the accompanying spectroscopic and computational study on the equiatomic i = j clusters [Klein et al., J. Chem. Phys. 156, 014302 (2022)]. [ABSTRACT FROM AUTHOR]

We investigated the N2 adsorption behavior of bimetallic rhodium–iron cluster cations [RhiFej(N2)m]+ by means of InfraRed MultiplePhotoDissociation (IR-MPD) spectroscopy in comparison with density functional theory (DFT) modeling. This approach allows us to refine our kinetic results [Ehrhard et al., J. Chem. Phys. (in press)] to enhance our conclusions. We focus on a selection of cluster adsorbate complexes within the ranges of i = j = 3–8 and m = 1–10. For i = j = 3, 4, DFT suggests alloy structures in the case of i = j = 4 of high (D2d) symmetry: Rh–Fe bonds are preferred instead of Fe–Fe bonds or Rh–Rh bonds. N2 adsorption and IR-MPD studies reveal strong evidence for preferential adsorption to Rh sites and mere secondary adsorption to Fe. In some cases, we observe adsorption isomers. With the help of modeling the cluster adsorbate complex [Rh3Fe3(N2)7]+, we find clear evidence that the position of IR bands allows for an element specific assignment of an adsorption site. We transfer these findings to the [Rh4Fe4(N2)m]+ cluster adsorbate complex where the first four N2 molecules are exclusively adsorbed to the Rh atoms. The spectra of the larger adsorbates reveal N2 adsorption onto the Fe atoms. Thus, the spectroscopic findings are well interpreted for the smaller clusters in terms of computed structures, and both compare well to those of our accompanying kinetic study [Ehrhard et al., J. Chem. Phys. (in press)]. In contrast to our previous studies of bare rhodium clusters, the present investigations do not provide any indication for a spin quench in [RhiFej(N2)m]+ upon stepwise N2 adsorption. [ABSTRACT FROM AUTHOR]

We present a study of stepwise cryogenic N2 adsorption on size-selected Fen+ (n = 8–20) clusters within a hexapole collision cell held at T = 21–28 K. The stoichiometries of the observed adsorption limits and the kinetic fits of stepwise N2 uptake reveal cluster size-dependent variations that characterize four structural regions. Exploratory density functional theory studies support tentative structural assignment in terms of icosahedral, hexagonal antiprismatic, and closely packed structural motifs. There are three particularly noteworthy cases, Fe13+ with a peculiar metastable adsorption limit, Fe17+ with unprecedented nitrogen phobia (inefficient N2 adsorption), and Fe18+ with an isomeric mixture that undergoes relaxation upon considerable N2 uptake. [ABSTRACT FROM AUTHOR]

Infrared photodissociation (IR-PD) spectra of iron cluster dinitrogen adsorbate complexes [Fen(N2)m]+ for n = 8–20 reveal slightly redshifted IR active bands in the region of 2200–2340 cm−1. These bands mostly relate to stretching vibrations of end-on coordinated N2 chromophores, a μ1,end end-on binding motif. Density Functional Theory (DFT) modeling and detailed analysis of n = 13 complexes are consistent with an icosahedral Fe13+ core structure. The first adsorbate shell closure at (n,m) = (13,12)—as recognized by the accompanying paper on the kinetics of N2 uptake by cationic iron clusters—comes with extensive IR-PD band broadening resulting from enhanced couplings among adjacent N2 adsorbates. DFT modeling predicts spin quenching by N2 adsorption as evidenced by the shift of the computed spin minima among possible spin states (spin valleys). The IR-PD spectrum of (17,1) surprisingly reveals an absence of any structure but efficient non-resonant fragmentation, which might indicate some weakly bound (roaming) N2 adsorbate. The multiple and broad bands of (17,m) for all other cases than (17,1) and (17,7) indicate a high degree of variation in N2 binding motifs and couplings. In contrast, the (17,7) spectrum of six sharp bands suggests pairwise equivalent N2 adsorbates. The IR-PD spectra of (18,m) reveal additional features in the 2120–2200 cm−1 region, which we associate with a μ1,side side-on motif. Some additional features in the (18,m) spectra at high N2 loads indicate a μ1,tilt tilted end-on adsorption motif. [ABSTRACT FROM AUTHOR]

We present the RASS-MCMF catalogue of 8449 X-ray selected galaxy clusters over 25 000 deg2 of extragalactic sky. The accumulation of deep multiband optical imaging data, the development of the Multi-Component Matched Filter (MCMF) cluster confirmation algorithm, and the release of the DESI Legacy Survey DR10 catalogue makes it possible – for the first time, more than 30 yr after the launch of the ROSAT X-ray satellite – to identify the majority of the galaxy clusters detected in the second ROSAT All-Sky-Survey (RASS) source catalogue (2RXS). The resulting 90 per cent pure RASS-MCMF catalogue is the largest intracluster medium (ICM)-selected cluster sample to date. RASS-MCMF probes a large dynamic range in cluster mass spanning from galaxy groups to the most massive clusters. The cluster redshift distribution peaks at |$z$| ∼ 0.1 and extends to redshifts |$z$| ∼ 1. Out to |$z$| ∼ 0.4, the RASS-MCMF sample contains more clusters per redshift interval (d N /d z) than any other ICM-selected sample. In addition to the main sample, we present two subsamples with 6912 and 5506 clusters, exhibiting 95 per cent and 99 per cent purity, respectively. We forecast the utility of the sample for a cluster cosmological study, using realistic mock catalogues that incorporate most observational effects, including the X-ray exposure time and background variations, the existence likelihood selection and the impact of the optical cleaning with the algorithm MCMF. Using realistic priors on the observable–mass relation parameters from a DES-based weak lensing analysis, we estimate the constraining power of the RASS-MCMF×DES sample to be of 0.026, 0.033, and 0.15 (1σ) on the parameters Ωm, σ8, and |$w$|⁠ , respectively. [ABSTRACT FROM AUTHOR]

Purpose: Identification of patients at risk of complicated or more severe COVID-19 is of pivotal importance, since these patients might require monitoring, antiviral treatment, and hospitalization. In this study, we prospectively evaluated the SACOV-19 score for its ability to predict complicated or more severe COVID-19. Methods: In this prospective multicenter study, we included 124 adult patients with acute COVID-19 in three German hospitals, who were diagnosed in an early, uncomplicated stage of COVID-19 within 72 h of inclusion. We determined the SACOV-19 score at baseline and performed a follow-up at 30 days. Results: The SACOV-19 score's AUC was 0.816. At a cutoff of > 3, it predicted deterioration to complicated or more severe COVID-19 with a sensitivity of 94% and a specificity of 55%. It performed significantly better in predicting complicated COVID-19 than the random tree-based SACOV-19 predictive model, the CURB-65, 4C mortality, or qCSI scores. Conclusion: The SACOV-19 score is a feasible tool to aid decision making in acute COVID-19. [ABSTRACT FROM AUTHOR]

Background: Brain pericytes participate in the regulation of cerebral blood flow and the maintenance of blood–brain barrier integrity. Because of their perivascular localization, their receptor repertoire, and their potential ability to respond to inflammatory and infectious stimuli by producing various cytokines and chemokines, these cells are also thought to play an active role in the immune response to brain infections. This assumption is mainly supported by in vitro studies, investigations in in vivo disease models are largely missing. Here, we analysed the role of brain pericytes in pneumococcal meningitis, in vitro and in vivo in two animal models of pneumococcal meningitis. Methods: Primary murine and human pericytes were stimulated with increasing concentrations of different serotypes of Streptococcus pneumoniae in the presence or absence of Toll-like receptor inhibitors and their cell viability and cytokine production were monitored. To gain insight into the role of pericytes in brain infection in vivo, we performed studies in a zebrafish embryo model of pneumococcal meningitis in which pericytes were pharmacologically depleted. Furthermore, we analyzed the impact of genetically induced pericyte ablation on disease progression, intracranial complications, and brain inflammation in an adult mouse model of this disease. Results: Both murine and human pericytes reacted to pneumococcal exposure with the release of selected cytokines. This cytokine release is pneumolysin-dependent, TLR-dependent in murine (but not human) pericytes and can be significantly increased by macrophage-derived IL-1b. Pharmacological depletion of pericytes in zebrafish embryos resulted in increased cerebral edema and mortality due to pneumococcal meningitis. Correspondingly, in an adult mouse meningitis model, a more pronounced blood–brain barrier disruption and leukocyte infiltration, resulting in an unfavorable disease course, was observed following genetic pericyte ablation. The degree of leukocyte infiltration positively correlated with an upregulation of chemokine expression in the brains of pericyte-depleted mice. Conclusions: Our findings show that pericytes play a protective role in pneumococcal meningitis by impeding leukocyte migration and preventing blood–brain barrier breaching. Thus, preserving the integrity of the pericyte population has the potential as a new therapeutic strategy in pneumococcal meningitis. [ABSTRACT FROM AUTHOR]

Tumor development and progression is shaped by the tumor microenvironment (TME), a heterogeneous assembly of infiltrating and resident host cells, their secreted mediators and intercellular matrix. In this context, tumors are infiltrated by various immune cells with either pro-tumoral or anti-tumoral functions. Recently, we published our non-invasive immunization platform DIVA suitable as a therapeutic vaccination method, further optimized by repeated application (DIVA² ). In our present work, we revealed the therapeutic effect of DIVA² in an MC38 tumor model and specifically focused on the mechanisms induced in the TME after immunization. DIVA2 resulted in transient tumor control followed by an immune evasion phase within three weeks after the initial tumor inoculation. High-dimensional flow cytometry analysis and single-cell mRNA-sequencing of tumor-infiltrating leukocytes revealed cytotoxic CD8+ T cells as key players in the immune control phase. In the immune evasion phase, inflammatory CCR2+ PDL-1+ monocytes with immunosuppressive properties were recruited into the tumor leading to suppression of DIVA² -induced tumor-reactive T cells. Depletion of CCR2+ cells with specific antibodies resulted in prolonged survival revealing CCR2+ monocytes as important for tumor immune escape in the TME. In summary, the present work provides a platform for generating a strong antigen-specific primary and memory T cell immune response using the optimized transcutaneous immunization method DIVA² . This enables protection against tumors by therapeutic immune control of solid tumors and highlights the immunosuppressive influence of tumor infiltrating CCR2+ monocytes that need to be inactivated in addition for successful cancer immunotherapy [ABSTRACT FROM AUTHOR]

Introduction: Transcutaneous immunization (TCI) is a non-invasive vaccination method promoting strong cellular immune responses, crucial for the immunological rejection of cancer. Previously, we reported on the combined application of the TLR7 agonist imiquimod (IMQ) together with the anti-psoriatic drug dithranol as novel TCI platform DIVA (dithranol/IMQ based vaccination). In extension of this work, we further optimized DIVA in terms of drug dose, application pattern and established a new IMQ formulation. Methods: C57BL/6 mice were treated on the ear skin with dithranol and IMQ-containing ointments together with ovalbumin-derived peptides. T cell responses were determined by flow cytometry and IFN-γ ELISpot assay, local skin inflammation was characterized by ear swelling. Results: Applying the adjuvants on separate skin sites, a reduced number of specific CD8+ T cells with effector function was detectable, indicating that the local concurrence of adjuvants and peptide antigens is required for optimal vaccination. Likewise, changing the order of dithranol and IMQ resulted in an increased skin inflammatory reaction, but lower frequencies of antigen-specific CD8+ T cells indicating that dithranol is essential for superior T cell priming upon DIVA. Dispersing nanocrystalline IMQ in a spreadable formulation (IMI-Sol+) facilitated storage and application rendering comparable immune responses. DIVA applied one or two weeks after the first immunization resulted in a massive increase in antigen-specific T cells and up to a ten-fold increased memory response. Finally, in a prophylactic tumor setting, double but no single DIVA treatment enabled complete control of tumor growth, resulting in full tumor protection. Discussion: Taken together, the described optimized transcutaneous vaccination method leads to the generation of a strong cellular immune response enabling the effective control of tumor growth and has the potential for clinical development as a novel non-invasive vaccination method for peptide-based cancer vaccines in humans. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of community-acquired acute bacterial meningitis has decreased during the last decades. However, outcome remains poor with a significant proportion of patients not surviving and up to 50% of survivors suffering from long-term sequelae. These guidelines were developed by the Deutsche Gesellschaft für Neurologie (DGN) under guidance of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) to guide physicians through diagnostics and treatment of adult patients with acute bacterial meningitis. Recommendations: The most important recommendations are: (i) In patients with suspected acute bacterial meningitis, we recommend that lumbar cerebrospinal fluid (with simultaneous collection of serum to determine the cerebrospinal fluid-serum glucose index and blood cultures) is obtained immediately after the clinical examination (in the absence of severely impaired consciousness, focal neurological deficits, and/or new epileptic seizures). (ii) Next, we recommend application of dexamethasone and empiric antibiotics intravenously. (iii) The recommended initial empiric antibiotic regimen consists of ampicillin and a group 3a cephalosporin (e.g., ceftriaxone). (iv) In patients with severely impaired consciousness, new onset focal neurological deficits (e.g. hemiparesis) and/or patients with newly occurring epileptic seizures, we recommend that dexamethasone and antibiotics are started immediately after the collection of blood; we further recommend that —if the imaging findings do not indicate otherwise —a lumbar CSF sample is taken directly after imaging. (v) Due to the frequent occurrence of intracranial and systemic complications, we suggest that patients with acute bacterial meningitis are treated at an intensive care unit in the initial phase of the disease. In the case of impaired consciousness, we suggest that this is done at an intensive care unit with experience in the treatment of patients with severe CNS diseases. Conclusions: The German S2k-guidelines give up to date recommendations for workup, diagnostics and treatment in adult patients with acute bacterial meningitis. [ABSTRACT FROM AUTHOR]

Background: Brain pericytes participate in the regulation of cerebral blood flow and the maintenance of blood–brain barrier integrity. Because of their perivascular localization, their receptor repertoire, and their potential ability to respond to inflammatory and infectious stimuli by producing various cytokines and chemokines, these cells are also thought to play an active role in the immune response to brain infections. This assumption is mainly supported by in vitro studies, investigations in in vivo disease models are largely missing. Here, we analysed the role of brain pericytes in pneumococcal meningitis, in vitro and in vivo in two animal models of pneumococcal meningitis. Methods: Primary murine and human pericytes were stimulated with increasing concentrations of different serotypes of Streptococcus pneumoniae in the presence or absence of Toll-like receptor inhibitors and their cell viability and cytokine production were monitored. To gain insight into the role of pericytes in brain infection in vivo, we performed studies in a zebrafish embryo model of pneumococcal meningitis in which pericytes were pharmacologically depleted. Furthermore, we analyzed the impact of genetically induced pericyte ablation on disease progression, intracranial complications, and brain inflammation in an adult mouse model of this disease. Results: Both murine and human pericytes reacted to pneumococcal exposure with the release of selected cytokines. This cytokine release is pneumolysin-dependent, TLR-dependent in murine (but not human) pericytes and can be significantly increased by macrophage-derived IL-1b. Pharmacological depletion of pericytes in zebrafish embryos resulted in increased cerebral edema and mortality due to pneumococcal meningitis. Correspondingly, in an adult mouse meningitis model, a more pronounced blood–brain barrier disruption and leukocyte infiltration, resulting in an unfavorable disease course, was observed following genetic pericyte ablation. The degree of leukocyte infiltration positively correlated with an upregulation of chemokine expression in the brains of pericyte-depleted mice. Conclusions: Our findings show that pericytes play a protective role in pneumococcal meningitis by impeding leukocyte migration and preventing blood–brain barrier breaching. Thus, preserving the integrity of the pericyte population has the potential as a new therapeutic strategy in pneumococcal meningitis. [ABSTRACT FROM AUTHOR]

The analysis of the secretome provides important information on proteins defining intercellular communication and the recruitment and behavior of cells in specific tissues. Especially in the context of tumors, secretome data can support decisions for diagnosis and therapy. The mass spectrometry–based analysis of cell-conditioned media is widely used for the unbiased characterization of cancer secretomes in vitro. Metabolic labeling using azide-containing amino acid analogs in combination with click chemistry facilitates this type of analysis in the presence of serum, preventing serum starvation-induced effects. The modified amino acid analogs, however, are less efficiently incorporated into newly synthesized proteins and may perturb protein folding. Combining transcriptome and proteome analysis, we elucidate in detail the effects of metabolic labeling with the methionine analog azidohomoalanine (AHA) on gene and protein expression. Our data reveal that 15–39% of the proteins detected in the secretome displayed changes in transcript and protein expression induced by AHA labeling. Gene Ontology (GO) analyses indicate that metabolic labeling using AHA leads to induction of cellular stress and apoptosis-related pathways and provide first insights on how this affects the composition of the secretome on a global scale. Key messages: Azide-containing amino acid analogs affect gene expression profiles. Azide-containing amino acid analogs influence cellular proteome. Azidohomoalanine labeling induces cellular stress and apoptotic pathways. Secretome consists of proteins with dysregulated expression profiles. [ABSTRACT FROM AUTHOR]

We present the splashback radius measurements around the SRG/eROSITA eFEDS X-ray selected galaxy clusters by cross-correlating them with HSC S19A photometric galaxies. The X-ray selection is expected to be less affected by systematics related to projection that affects optical cluster finder algorithms. We use a nearly volume-limited sample of 109 galaxy clusters selected in 0.5–2.0 keV band having luminosity |$L_X \gt 10^{43.5}\, {\rm erg \, s}^{-1}\, h^{-2}$| within the redshift z < 0.75 and obtain measurements of the projected cross-correlation with a signal to noise of 17.43. We model our measurements to infer a 3D profile and find that the steepest slope is sharper than −3 and associate the location with the splashback radius. We infer the value of the 3D splashback radius |$r_{\rm sp} = 1.45^{+0.30}_{-0.26}\, h^{-1}\, {\rm Mpc}$|. We also measure the weak-lensing signal of the galaxy clusters and obtain halo mass |$\log [M_{\rm 200m}/ h^{-1}\, {\rm M_\odot }] = 14.52 \pm 0.06$| using the HSC-S16A shape catalogue data at the median redshift z  = 0.46 of our cluster sample. We compare our r sp values with the spherical overdensity boundary |$r_{\rm 200m} = 1.75 \pm 0.08\, h^{-1} \, {\rm Mpc}$| based on the halo mass, which is consistent within 1.2σ with the ΛCDM predictions. Our constraints on the splashback radius, although broad, are the best measurements thus far obtained for an X-ray selected galaxy cluster sample. [ABSTRACT FROM AUTHOR]

We present the first cosmological study of a sample of eROSITA clusters, which were identified in the eROSITA Final Equatorial Depth Survey (eFEDS). In a joint selection on X-ray and optical observables, the sample contains 455 clusters within a redshift range of 0.1 < z < 1.2, of which 177 systems are covered by the public data from the Hyper Suprime-Cam (HSC) survey that enables uniform weak-lensing cluster mass constraints. With minimal assumptions, at each cluster redshift we empirically model (1) the scaling relations between the cluster halo mass and the observables, which include the X-ray count rate, the optical richness, and the weak-lensing mass, and (2) the X-ray selection in terms of the completeness function |$\mathcal {C}$|⁠. Using the richness distribution of the clusters, we directly measure the X-ray completeness and adopt those measurements as informative priors for the parameters of |$\mathcal {C}$|⁠. In a blinded analysis, we obtain the cosmological constraints |$\Omega _{\mathrm{m}}= 0.245^{+0.048}_{-0.058}$|⁠ , |$\sigma _{8}= 0.833^{+0.075}_{-0.063}$|⁠ , and |$S_{8}\equiv \sigma _{8}\left(\Omega _{\mathrm{m}}/0.3\right)^{0.3}= 0.791^{+0.028}_{-0.031}$| in a flat ΛCDM cosmology. Extending to a flat w CDM cosmology leads to the constraint on the equation of state parameter of the dark energy of w  = −1.25 ± 0.47. The eFEDS constraints are in good agreement with the results from the Planck mission, the galaxy–galaxy lensing and clustering analysis of the Dark Energy Survey, and the cluster abundance analysis of the SPT-SZ survey at a level of ≲ 1σ. With the empirical modelling, this work presents the first fully self-consistent cosmological constraints based on a synergy between wide-field X-ray and weak lensing surveys. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic and associated public health and social measures, decreasing patient numbers have been described in various healthcare settings in Germany, including emergency care. This could be explained by changes in disease burden, e.g. due to contact restrictions, but could also be a result of changes in utilisation behaviour of the population. To better understand those dynamics, we analysed routine data from emergency departments to quantify changes in consultation numbers, age distribution, disease acuity and day and hour of the day during different phases of the COVID-19 pandemic. Methods: We used interrupted time series analyses to estimate relative changes for consultation numbers of 20 emergency departments spread throughout Germany. For the pandemic period (16-03-2020 – 13-06-2021) four different phases of the COVID-19 pandemic were defined as interruption points, the pre-pandemic period (06-03-2017 – 09-03-2020) was used as the reference. Results: The most pronounced decreases were visible in the first and second wave of the pandemic, with changes of − 30.0% (95%CI: − 32.2%; − 27.7%) and − 25.7% (95%CI: − 27.4%; − 23.9%) for overall consultations, respectively. The decrease was even stronger for the age group of 0–19 years, with − 39.4% in the first and − 35.0% in the second wave. Regarding acuity levels, consultations assessed as urgent, standard, and non-urgent showed the largest decrease, while the most severe cases showed the smallest decrease. Conclusions: The number of emergency department consultations decreased rapidly during the COVID-19 pandemic, without extensive variation in the distribution of patient characteristics. Smallest changes were observed for the most severe consultations and older age groups, which is especially reassuring regarding concerns of possible long-term complications due to patients avoiding urgent emergency care during the pandemic. [ABSTRACT FROM AUTHOR]

Background: Low energy falls (LEF) in older adults constitute a relevant cause for emergency department (ED) visits, hospital admission and in-hospital mortality. Patient-reported outcome measures containing information about patients' medical, mental and social health problems might support disposition and therapy decisions. We investigated the value of a tablet-based (self-)assessment in predicting hospital admission and in-hospital mortality. Methods: Patients 65 years or older, consecutively presenting with LEF to our level I trauma center ED (from November 2020 to March 2021), were eligible for inclusion in this prospective observational study. The primary endpoint was hospital admission; secondary endpoints were in-hospital mortality and the use of the tablet for self-reported assessment. Multivariate logistic regression models were calculated to measure the association between clinical findings and endpoints. Results: Of 618 eligible patients, 201 patients were included. The median age was 82 years (62.7% women). The hospital admission rate was 45.3% (110/201), with an in-hospital mortality rate of 3.6% (4/110). Polypharmacy (odds ratio (OR): 8.48; 95% confidence interval (95%CI) 1.21–59.37, p = 0.03), lower emergency severity index (ESI) scores (OR: 0.33; 95%CI 0.17–0.64, p = 0.001) and increasing injury severity score (ISS) (OR: 1.54; 95%CI 1.32–1.79, p < 0.001) were associated with hospital admission. The Charlson comorbidity index (CCI) was significantly associated with in-hospital mortality (OR: 2.60; 95%CI: 1.17–5.81, p = 0.03). Increasing age (OR: 0.94; 95%CI: 0.89–0.99, p = 0.03) and frailty (OR: 0.71; 95%CI: 0.51–0.99, p = 0.04) were associated with the incapability of tablet use. Conclusions: The severity of fall-related injuries and the clinical acuity are easily accessible, relevant predictors for hospital admission. Tablet-based (self-)assessment may be feasible and acceptable during ED visits and might help facilitate comprehensive geriatric assessments during ED stay. [ABSTRACT FROM AUTHOR]

Introduction: Artificial Neural Networks (ANN) are increasingly used in metabolomics but are hard to interpret. Objectives: We aimed at developing a feature impact score that is model-agnostic, simple, and interpretable. Methods: Feature Impact Assessment (FIA) is calculated by varying combinations of features within their observed value range and checking for changes in prediction outcomes. FIA was implemented in R and tested on metabolomics datasets. Results: FIA exceeded LIME and SHAP in selecting biologically meaningful features. Values were comparable across different ANN architectures. Conclusion: FIA is a novel score ranking feature impact, helping interpreting ANN in the metabolomics field. [ABSTRACT FROM AUTHOR]

Background and purpose: Idiopathic facial palsy (IFP) accounts for over 60% of peripheral facial palsy (FP) cases. The cause of IFP remains to be determined. Possible etiologies are nerve swelling due to inflammation and/or viral infection. In this study, we applied an integrative mass spectrometry approach to identify possibly altered protein patterns in the cerebrospinal fluid (CSF) of IFP patients. Methods: We obtained CSF samples from 34 patients with FP. In four patients, varicella‐zoster virus was the cause (VZV‐FP). Among the 30 patients diagnosed with IFP, 17 had normal CSF parameters, five had slightly elevated CSF cell counts and normal or elevated CSF protein, and eight had normal CSF cell counts but elevated CSF protein. Five patients with primary headache served as controls. All samples were tested for viral pathogens by PCR and subjected to liquid chromatography tandem mass spectrometry and bioinformatics analysis and multiplex cytokine/chemokine arrays. Results: All CSF samples, except those from VZV‐FP patients, were negative for all tested pathogens. The protein composition of CSF samples from IFP patients with normal CSF was comparable to controls. IFP patients with elevated CSF protein showed dysregulated proteins involved in inflammatory pathways, findings which were similar to those in VZV‐FP patients. Multiplex analysis revealed similarly elevated cytokine levels in the CSF of IFP patients with elevated CSF protein and VZV‐FP. Conclusions: Our study revealed a subgroup of IFP patients with elevated CSF protein that showed upregulated inflammatory pathways, suggesting an inflammatory/infectious cause. However, no evidence for an inflammatory cause was found in IFP patients with normal CSF. [ABSTRACT FROM AUTHOR]

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Background and purpose: Meningitis and encephalitis are potentially life‐threatening diseases that require fast and accurate diagnostics and therapy. The value of polymerase chain reaction (PCR) multiplex testing in clinical practice is still a matter of debate. This study aims to evaluate its benefits and limitations in emergency patients. Methods: We assessed the value of a meningoencephalitis PCR array in the clinical routine of an emergency department. Results: Of 1578 emergency patients who received a lumbar puncture, 43% received it for a clinically suspected central nervous system (CNS) infection. After initial workup for cerebrospinal fluid (CSF) cell count, protein and glucose, a CNS infection was still considered likely in 307 patients. In these patients, further microbiologic workup was performed. A total of 230 samples were examined by PCR and a pathogen was detected in 66 of these samples. In the case of a positive microbiologic result, a comparison between PCR array and standard method was available for 59 samples, which demonstrated an overcall agreement of 80% (n = 47/59). Of interest, exclusively array‐positive results were observed for patients with meningitis found to be positive for Streptococcus pneumoniae; four out of five patients had been treated with antibiotics before the lumbar puncture. In samples with normal CSF cell count only two positive array results were obtained, both for human herpesvirus 6, and these were not clinically relevant. Conclusion: Our data suggest that the array substantially contributes to a detection of pathogens in patients with suspected CNS infection and seems of particular interest in patients with acute bacterial meningitis under empiric antibiotic treatment. In CSF samples with normal cell count, it might be dispensable. [ABSTRACT FROM AUTHOR]

Background: Degradation of the endothelial protective glycocalyx layer during COVID-19 infection leads to shedding of major glycocalyx components. These circulating proteins and their degradation products may feedback on immune and endothelial cells and activate molecular signaling cascades in COVID-19 associated microvascular injury. To test this hypothesis, we measured plasma glycocalyx components in patients with SARS-CoV-2 infection of variable disease severity and identified molecular signaling networks activated by glycocalyx components in immune and endothelial cells. Methods: We studied patients with RT-PCR confirmed COVID-19 pneumonia, patients with COVID-19 Acute Respiratory Distress Syndrome (ARDS) and healthy controls (wildtype, n=20 in each group) and measured syndecan-1, heparan sulfate and hyaluronic acid. The in-silico construction of signaling networks was based on RNA sequencing (RNAseq) of mRNA transcripts derived from blood cells and of miRNAs isolated from extracellular vesicles from the identical cohort. Differentially regulated RNAs between groups were identified by gene expression analysis. Both RNAseq data sets were used for network construction of circulating glycosaminoglycans focusing on immune and endothelial cells. Results: Plasma concentrations of glycocalyx components were highest in COVID-19 ARDS. Hyaluronic acid plasma levels in patients admitted with COVID-19 pneumonia who later developed ARDS during hospital treatment (n=8) were significantly higher at hospital admission than in patients with an early recovery. RNAseq identified hyaluronic acid as an upregulator of TLR4 in pneumonia and ARDS. In COVID-19 ARDS, syndecan-1 increased IL-6, which was significantly higher than in pneumonia. In ARDS, hyaluronic acid activated NRP1, a co-receptor of activated VEGFA, which is associated with pulmonary vascular hyperpermeability and interacted with VCAN (upregulated), a proteoglycan important for chemokine communication. Conclusions: Circulating glycocalyx components in COVID-19 have distinct biologic feedback effects on immune and endothelial cells and result in upregulation of key regulatory transcripts leading to further immune activation and more severe systemic inflammation. These consequences are most pronounced during the early hospital phase of COVID-19 before pulmonary failure develops. Elevated levels of circulating glycocalyx components may early identify patients at risk for microvascular injury and ARDS. The timely inhibition of glycocalyx degradation could provide a novel therapeutic approach to prevent the development of ARDS in COVID-19. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine the long-term results of implants in orbital reconstruction after exenteration. Materials and Methods: From 1998 to 2012, patients undergoing implant-supported rehabilitation after subtotal or total exenteration due to a tumor were included in a retrospective study. All the patients were evaluated for soft tissue reconstruction, irradiation, complications, abutments, hygiene index, implant mobility, and long-term success. Results: Forty-eight patients (aged between 27 and 81 years) were selected. A total of 187 implants were inserted. All the patients were supplied with epitheses after implantation in the long term. Of the 187 implants, nine implants placed on five patients were lost. The mean follow-up period was 34 months (ranging from 6 to 144 months). The 5-year survival rate was 88%. Conclusion: On the basis of this retrospective study of 48 patients with 187 implants, the following observations were made: (1) the 5-year survival of implants in nonradiated bone was 92%, and (2) the 5-year survival of implants in radiated bone was 86%. Extraoral implants should be presented as an option in orbital rehabilitation after exenteration. [ABSTRACT FROM AUTHOR]

The article focuses on addressing concerns raised about preanalytical issues and laboratory techniques affecting cerebrospinal fluid (CSF) studies. Topics include the criticality of preanalytical time, the significance of laboratory techniques, such as manual cell counting, and the need for researchers to consider these factors when interpreting CSF analysis results.

Pneumococcal meningitis is associated with dysregulation of the coagulation cascade. Previously, we detected upregulation of cerebral plasminogen activator inhibitor-2 (PAI-2) mRNA expression during pneumococcal meningitis. Diverse functions have been ascribed to PAI-2, but its role remains unclear. We analyzed the function of SERPINB2 (coding for PAI-2) in patients with bacterial meningitis, in a well-established pneumococcal meningitis mouse model, using Serpinb2 knockout mice, and in vitro in wt and PAI-2-deficient bone marrow-derived macrophages (BMDMs). We measured PAI-2 in cerebrospinal fluid of patients, and performed functional, histopathological, protein and mRNA expression analyses in vivo and in vitro. We found a substantial increase of PAI-2 concentration in CSF of patients with pneumococcal meningitis, and up-regulation and increased release of PAI-2 in mice. PAI-2 deficiency was associated with increased mortality in murine pneumococcal meningitis and cerebral hemorrhages. Serpinb2−/− mice exhibited increased C5a levels, but decreased IL-10 levels in the brain during pneumococcal infection. Our in vitro experiments confirmed increased expression and release of PAI-2 by wt BMDM and decreased IL-10 liberation by PAI-2-deficient BMDM upon pneumococcal challenge. Our data show that PAI-2 is elevated during in pneumococcal meningitis in humans and mice. PAI-2 deficiency causes an inflammatory imbalance, resulting in increased brain pathology and mortality. [ABSTRACT FROM AUTHOR]

Background: In this retrospective routine data analysis, we investigate the number of emergency department (ED) consultations during the COVID-19 pandemic of 2020 in Germany compared to the previous year with a special focus on numbers of myocardial infarction and acute heart failure. Methods: Aggregated case numbers for the two consecutive years 2019 and 2020 were obtained from 24 university hospitals and 9 non-university hospitals in Germany and assessed by age, gender, triage scores, disposition, care level and by ICD-10 codes including the tracer diagnoses myocardial infarction (I21) and heart failure (I50). Results: A total of 2,216,627 ED consultations were analyzed, of which 1,178,470 occurred in 2019 and 1,038,157 in 2020. The median deviation in case numbers between 2019 and 2020 was − 14% [CI (− 11)–(− 16)]. After a marked drop in all cases in the first COVID-19 wave in spring 2020, case numbers normalized during the summer. Thereafter starting in calendar week 39 case numbers constantly declined until the end of the year 2020. The decline in case numbers predominantly concerned younger [− 16%; CI (− 13)–(− 19)], less urgent [− 18%; CI (− 12)–(− 22)] and non-admitted cases [− 17%; CI (− 13)–(− 20)] in particular during the second wave. During the entire observation period admissions for chest pain [− 13%; CI (− 21)–2], myocardial infarction [− 2%; CI (− 9)–11] and heart failure [− 2%; CI (− 10)–6] were less affected and remained comparable to the previous year. Conclusions: ED visits were noticeably reduced during both SARS-CoV-2 pandemic waves in Germany but cardiovascular diagnoses were less affected and no refractory increase was noted. However, long-term effects cannot be ruled out and need to be analysed in future studies. [ABSTRACT FROM AUTHOR]

Those changes have now been updated in the HTML and PDF version of this Article. Correction to: I npj Vaccines i https://doi.org/10.1038/s41541-022-00530-9, published online 24 September 2022 In the original version of this Article, Jonas Pielenhofer and Luise Meiser were mistakenly omitted from the Acknowledgements. The original article can be found online at https://doi.org/10.1038/s41541-022-00530-9. [Extracted from the article]

Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our present work, we combine the anti-psoriatic agent dithranol with IMQ-TCI to boost vaccination efficacy (Dithranol/IMQ-based transcutaneous vaccination (DIVA)). Using ovalbumin-derived peptides as model antigens in mice, DIVA induced superior cytolytic CD8+ T cells and CD4+ T cells with a TH1 cytokine profile in the priming as well as in the memory phase. Regarding the underlying mechanisms, dithranol induced an oxidant-dependent, monocyte-attracting inflammatory milieu in the skin boosting TLR7-dependent activation of dendritic cells and macrophages leading to superior T cell priming and protective immunity in vaccinia virus infection. In conclusion, we introduce the non-invasive vaccination method DIVA to induce strong primary and memory T cell responses upon a single local treatment. This work provides relevant insights in cutaneous vaccination approaches, paving the way for clinical development in humans. [ABSTRACT FROM AUTHOR]

Background: Symptoms caused by cardiac arrhythmia are common problems that lead to presentation to the emergency department. However, the prevalence of pathological heart rhythm in patients triaged for cardiac arrhythmia in the emergency department remains up to now unknown. Methods and results: In this retrospective study, patients triaged for cardiac arrhythmia admitted to the interdisciplinary emergency department of the Ludwig-Maximilians University Hospital in Munich within 1 year were included. Subsequently, cardiac rhythm in the 12-lead electrocardiogram, clinical presentation, admission rate, and diagnosis at discharge was analyzed. A total of 558 out of 39,798 patients were triaged for cardiac arrhythmia. Of these 42.3% of patients showed a pathological heart rhythm on the initial electrocardiogram (66.9% atrial fibrillation, 16.5% atrial flutter, 16.5% others). About 80% presented in emergency severity index III (many resources are needed without critical vitals) conditions. Sixty-two percent of the pathological electrocardiogram group and 60% of the sinus rhythm group of patients were admitted to the hospital, and 34.7% with pathological electrocardiogram underwent invasive investigations (16.8% in the sinus rhythm group). In 43.4% of patients, the diagnosis of cardiac arrhythmia was already known from previous medical contacts. Conclusion: A total of 1.8% of patients who presented to our interdisciplinary emergency department were triaged for cardiac arrhythmia. With 49.5%, the hospital admission rate was quite high but the patients presented to the emergency department in our cohort were rarely in critical condition. As a high percentage of our cohort had a history of cardiac arrhythmia, better outpatient management is needed for these patients to reduce emergency department visits and save resources. [ABSTRACT FROM AUTHOR]

Considering the role of healthcare workers (HCW) in promoting vaccine uptake and previously recorded hesitancy among HCW, we aim to examine the COVID-19 vaccination intent and status of HCW through a cross-sectional anonymous online survey at LMU University Hospital in Munich. Data collection was informed by the Health Belief Model (HBM) and focused on vaccination intent, status and on potential factors affecting the decision-making process. In total, 2555 employees completed the questionnaire. Our data showed that an approving attitude towards recommended vaccines and having received an influenza vaccine in the previous winter were strongly associated with COVID-19 vaccination intent. Further, a positive COVID-19 vaccination status was associated with a higher likelihood of approving the extension of the validity of non-pharmaceutical interventions at the workplace. Our HBM-analysis demonstrated strong associations between the perceived benefits and barriers and COVID-19 vaccination intent. Unchanged or low perceived susceptibility and severity were associated with refusal or indecisiveness. Our findings highlight the factors associated with the decision regarding a COVID-19 vaccine and indicate a pattern-like behavior in the acceptance of novel vaccines by HCW. These insights can help inform the communication aims of vaccination campaigns among HCW within similar organizational contexts or in future outbreaks. [ABSTRACT FROM AUTHOR]

The diagnosis of RCVS was established by the combination of the following findings: (i) thunderclap headache, (ii) vasoconstriction on cerebrovascular imaging, and (iii) rule out of subarachnoid haemorrhage by CT and lumbar puncture. Dear Sirs, Reversible cerebral vasoconstriction syndrome (RCVS) is an important differential diagnosis in patients with acute onset thunderclap headache [[1]]. Since the symptoms (acute severe headache) as well as the clinical and radiographic constellation were neither suggestive of intracranial hypertension nor typical MRI abnormalities reported in patients with intracranial hypertension, we saw no indication for further diagnostics and particularly treatment. To our knowledge, this is the first case describing thunderclap headache and RCVS after intravenous iron substitution in a patient with chronic iron deficiency anemia. [Extracted from the article]

The origin and function of CD20+ T cells are poorly understood. Here, we characterized CD20+ T cells in mice and humans and investigated how they are affected by anti-CD20 antibody treatment. We report that murine CD20+ T cells are unable to endogenously express the B cell lineage marker CD20; the development of CD20+ T cells in rodents requires the presence of CD20-expressing B cells. Our results demonstrated that both murine and human T cells acquire CD20 from B cells via trogocytosis while being activated by an antigen-presenting B cell. In patients with multiple sclerosis (MS) and mice with experimental autoimmune encephalomyelitis (EAE), expression of CD20 on T cells is associated with an up-regulation of activation markers, proinflammatory cytokines, and adhesion molecules, suggesting high pathogenic potential. Supporting this hypothesis, CD20+ T cells expand during active EAE in rodents; furthermore, adoptive transfer of CD20+ T cells into EAE-diseased mice worsened histological and clinical severity. Of direct therapeutic relevance, we demonstrate that the exclusive therapeutic elimination of CD20+ T cells effectively ameliorates EAE, independent of B cells. The results support the hypothesis that CD20+ T cells arise upon B cell–T cell interaction and that depletion of CD20+ T cells might contribute to the success of anti-CD20 antibody therapies in MS and other inflammatory disorders. Understanding CD20+ T cells in MS: Anti-CD20 monoclonal antibodies have shown some efficacy in patients with multiple sclerosis (MS). Although CD20 is mostly expressed by B cells, a subpopulation of CD20+ T cells has been identified. The origin of CD20+ T cells and their role in autoimmune diseases are not fully elucidated. Now, Ochs et al. found that T cells can acquire CD20 directly from B cells via tragocytosis. In mice with experimental autoimmune encephalomyelitis (EAE) and in patients with MS, expansion of this population contributes to the ongoing pathological inflammatory process. Selective depletion of CD20+ T cells in EAE mice had therapeutic effects, suggesting that elimination of this population might contribute to the efficacy of anti-CD20 therapies in MS. [ABSTRACT FROM AUTHOR]

Solvent-free inorganic-organic hybrid polymers were prepared for digital light processing (DLP) and ink-jet printing. The resins were characterized in terms of viscosity, surface tension, and refractive index. Optical bulk components were prepared with both printing techniques and compared regarding their surface roughness and optical scattering. The haze of DLP-samples can be avoided by inkjet 3D printing. Moreover, different quantum dots (QD) could be incorporated into resins; DLP resulted in complex 3D assemblies. Highlights: Synthesis of solvent-free inorganic-organic hybrid resins. Viscosity and surface tension suitable for DLP and ink-jet technology. Quantum dots can be incorporated to result in functional composites. Printing of bulk optical components. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the cost-effectiveness of supplemental short-protocol brain MRI after negative non-contrast CT for the detection of minor strokes in emergency patients with mild and unspecific neurological symptoms. Methods: The economic evaluation was centered around a prospective single-center diagnostic accuracy study validating the use of short-protocol brain MRI in the emergency setting. A decision-analytic Markov model distinguished the strategies "no additional imaging" and "additional short-protocol MRI" for evaluation. Minor stroke was assumed to be missed in the initial evaluation in 40% of patients without short-protocol MRI. Specialized post-stroke care with immediate secondary prophylaxis was assumed for patients with detected minor stroke. Utilities and quality-of-life measures were estimated as quality-adjusted life years (QALYs). Input parameters were obtained from the literature. The Markov model simulated a follow-up period of up to 30 years. Willingness to pay was set to $100,000 per QALY. Cost-effectiveness was calculated and deterministic and probabilistic sensitivity analysis was performed. Results: Additional short-protocol MRI was the dominant strategy with overall costs of $26,304 (CT only: $27,109). Cumulative calculated effectiveness in the CT-only group was 14.25 QALYs (short-protocol MRI group: 14.31 QALYs). In the deterministic sensitivity analysis, additional short-protocol MRI remained the dominant strategy in all investigated ranges. Probabilistic sensitivity analysis results from the base case analysis were confirmed, and additional short-protocol MRI resulted in lower costs and higher effectiveness. Conclusion: Additional short-protocol MRI in emergency patients with mild and unspecific neurological symptoms enables timely secondary prophylaxis through detection of minor strokes, resulting in lower costs and higher cumulative QALYs. Key Points: • Short-protocol brain MRI after negative head CT in selected emergency patients with mild and unspecific neurological symptoms allows for timely detection of minor strokes. • This strategy supports clinical decision-making with regard to immediate initiation of secondary prophylactic treatment, potentially preventing subsequent major strokes with associated high costs and reduced QALY. • According to the Markov model, additional short-protocol MRI remained the dominant strategy over wide variations of input parameters, even when assuming disproportionally high costs of the supplemental MRI scan. [ABSTRACT FROM AUTHOR]

CD4+CXCR5+Foxp3+ T-follicular regulatory (TFR) cells control the germinal center responses. Like T-follicular helper cells, they express high levels of N uclear F actor of A ctivated T -cells c1 , predominantly its short isoform NFATc1/αA. Ablation of NFATc1 in Tregs prevents upregulation of CXCR5 and migration of TFR cells into B-cell follicles. By contrast, constitutive active NFATc1/αA defines the surface density of CXCR5, whose level determines how deep a TFR migrates into the GC and how effectively it controls antibody production. As one type of effector Treg, TFR cells express B ly mphocyte- i nduced m aturation p rotein-1 (Blimp-1). Blimp-1 can directly repress Cxcr5 and NFATc1/αA is necessary to overcome this Blimp-1-mediated repression. Interestingly, Blimp-1 even reinforces the recruitment of NFATc1 to Cxcr5 by protein-protein interaction and by those means cooperates with NFATc1 for Cxcr5 transactivation. On the contrary, Blimp-1 is necessary to counterbalance NFATc1/αA and preserve the Treg identity. This is because although NFATc1/αA strengthens the follicular development of Tregs, it bears the inherent risk of causing an ex-Treg phenotype. [ABSTRACT FROM AUTHOR]