Showing papers by "Humboldt University of Berlin published in 2022"

Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders.

Abstract: BACKGROUND AND OBJECTIVES To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti-interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). METHODS Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab. RESULTS Patients received TCZ for 23.8 months (median; interquartile range 13.0-51.1 months), with an IV dose of 8.0 mg/kg (median; range 6-12 mg/kg) every 31.6 days (mean; range 26-44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5-5) to 0 (range 0-0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0-5] to 0 [range 0-4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0-3.0] to 0.2 [range 0-2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy. DISCUSSION This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.

SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. In this study, serum of Beta-infected patients revealed reduced cross-neutralization of wild-type virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wild type-elicited antibodies, including a public VH1-58 clonotype that targets the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift, with implications for design of next-generation vaccines and therapeutics.

The aquaponic principle—It is all about coupling

Abstract: The aquaponic principle is the coupling of animal aquaculture (e.g. fish) with plant production (e.g. vegetables) for saving resources. At present, various definitions of aquaponics exist, some bearing the risk of misinterpretation by dismissing the original meaning or being contradictory. In addition, there is no standard terminology for the aspects of coupling between the aquaponic subsystems. In this study, we addressed both issues. (1) We developed new or revised definitions that are summarised by: Aquaponic farming comprises aquaponics (which couples tank-based animal aquaculture with hydroponics) and trans-aquaponics, which extends aquaponics to tankless aquaculture as well as non-hydroponics plant cultivation methods. Within our conceptual system, the term aquaponics corresponds to the definitions of FAO and EU. (2) A system analysis approach was utilised to explore different aquaponic setups aiming to better describe the way aquaponic subsystems are connected. We introduced the new terms ‘coupling type’ and ‘coupling degree’, where the former qualitatively characterises the water-mediated connections of aquaponic subsystems. A system with on-demand nutrient water supply for the independent operating plant cultivation is an ‘on-demand coupled system’ and we propose to deprecate the counterintuitive term ‘decoupled system’ for this coupling type. The coupling degree comprises a set of parameters to quantitatively determine the coupling's efficiency of internal streams, for example, water and nutrients. This new framework forms a basis for improved communication, provides a uniform metric for comparing aquaponic facilities, and offers criteria for facility optimisation. In future system descriptions, it will simplify evaluation of the coupling's contribution to sustainability of aquaponics.

SUSY in the sky with gravitons

Abstract: A bstract Picture yourself in the wave zone of a gravitational scattering event of two massive, spinning compact bodies (black holes, neutron stars or stars). We show that this system of genuine astrophysical interest enjoys a hidden $$ \mathcal{N} $$ N = 2 supersymmetry, at least to the order of spin-squared (quadrupole) interactions in arbitrary D spacetime dimensions. Using the $$ \mathcal{N} $$ N = 2 supersymmetric worldline action, augmented by finite-size corrections for the non-Kerr black hole case, we build a quadratic-in-spin extension to the worldline quantum field theory (WQFT) formalism introduced in our previous work, and calculate the two bodies’ deflection and spin kick to sub-leading order in the post-Minkowskian expansion in Newton’s constant G . For spins aligned to the normal vector of the scattering plane we also obtain the scattering angle. All D -dimensional observables are derived from an eikonal phase given as the free energy of the WQFT that is invariant under the $$ \mathcal{N} $$ N = 2 supersymmetry transformations.

Which Picker Fits My Data? A Quantitative Evaluation of Deep Learning Based Seismic Pickers

Abstract: Seismic event detection and phase picking are the base of many seismological workflows. In recent years, several publications demonstrated that deep learning approaches significantly outperform classical approaches and even achieve human-like performance under certain circumstances. However, as most studies differ in the datasets and exact evaluation tasks studied, it is yet unclear how the different approaches compare to each other. Furthermore, there are no systematic studies how the models perform in a cross-domain scenario, i.e., when applied to data with different characteristics. Here, we address these questions by conducting a large-scale benchmark study. We compare six previously published deep learning models on eight datasets covering local to teleseismic distances and on three tasks: event detection, phase identification and onset time picking. Furthermore, we compare the results to a classical Baer-Kradolfer picker. Overall, we observe the best performance for EQTransformer, GPD and PhaseNet, with EQTransformer having a small advantage for teleseismic data. Furthermore, we conduct a cross-domain study, in which we analyze model performance on datasets they were not trained on. We show that trained models can be transferred between regions with only mild performance degradation, but not from regional to teleseismic data or vice versa. As deep learning for detection and picking is a rapidly evolving field, we ensured extensibility of our benchmark by building our code on standardized frameworks and making it openly accessible. This allows model developers to easily compare new models or evaluate performance on new datasets, beyond those presented here. Furthermore, we make all trained models available through the SeisBench framework, giving end-users an easy way to apply these models in seismological analysis.

Myocarditis following<scp>COVID</scp>‐19 vaccine: incidence, presentation, diagnosis, pathophysiology, therapy, and outcomes put into perspective. A clinical consensus document supported by the Heart Failure Association of the European Society of Cardiology (ESC) and the ESC Working Group on Myocardial and Pericardial Diseases

Abstract: Over 10 million doses of COVID-19 vaccines based on RNA technology, viral vectors, recombinant protein, and inactivated virus have been administered worldwide. Although generally very safe, post-vaccine myocarditis can result from adaptive humoral and cellular, cardiac-specific inflammation within days and weeks of vaccination. Rates of vaccine-associated myocarditis vary by age and sex with the highest rates in males between 12 and 39 years. The clinical course is generally mild with rare cases of left ventricular dysfunction, heart failure and arrhythmias. Mild cases are likely underdiagnosed as cardiac magnetic resonance imaging (CMR) is not commonly performed even in suspected cases and not at all in asymptomatic and mildly symptomatic patients. Hospitalization of symptomatic patients with electrocardiographic changes and increased plasma troponin levels is considered necessary in the acute phase to monitor for arrhythmias and potential decline in left ventricular function. In addition to evaluation for symptoms, electrocardiographic changes and elevated troponin levels, CMR is the best non-invasive diagnostic tool with endomyocardial biopsy being restricted to severe cases with heart failure and/or arrhythmias. The management beyond guideline-directed treatment of heart failure and arrhythmias includes non-specific measures to control pain. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs, and corticosteroids have been used in more severe cases, with only anecdotal evidence for their effectiveness. In all age groups studied, the overall risks of SARS-CoV-2 infection-related hospitalization and death are hugely greater than the risks from post-vaccine myocarditis. This consensus statement serves as a practical resource for physicians in their clinical practice, to understand, diagnose, and manage affected patients. Furthermore, it is intended to stimulate research in this area.

Privacy and Confidentiality in Process Mining: Threats and Research Challenges

Abstract: Privacy and confidentiality are very important prerequisites for applying process mining to comply with regulations and keep company secrets. This article provides a foundation for future research ...

A proteomic survival predictor for COVID-19 patients in intensive care

Abstract: Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.

A Nanohook‐Equipped Bionanocatalyst for Localized Near‐Infrared‐Enhanced Catalytic Bacterial Disinfection

Abstract: Novel bionanocatalysts have opened a new era in fighting multidrug-resistant (MDR) bacteria. They can kill bacteria by elevating the level of reactive oxygen species (ROS) in the presence of chemicals like H2 O2 . However, ROSs' ultrashort diffusion distance limit their bactericidal activity. We present a nanohook-equipped bionanocatalyst (Ni@Co-NC) with bacterial binding ability that shows robust ROS-generating capacity under physiological H2 O2 levels. The Ni@Co-NC's pH-dependent performance confines its effects to the biofilm microenvironment, leaving healthy tissue unaffected. Furthermore, it can generate heat upon NIR laser irradiation, enhancing its catalytic performance while achieving heat ablation against bacteria. With the Ni@Co-NC's synergistic effects, bacterial populations fall by >99.99 %. More surprisingly, the mature biofilm shows no recurrence after treatment with the Ni@Co-NC, demonstrating its tremendous potential for treating MDR bacterial related infections.

The bouba/kiki effect is robust across cultures and writing systems.

Abstract: The bouba/kiki effect-the association of the nonce word bouba with a round shape and kiki with a spiky shape-is a type of correspondence between speech sounds and visual properties with potentially deep implications for the evolution of spoken language. However, there is debate over the robustness of the effect across cultures and the influence of orthography. We report an online experiment that tested the bouba/kiki effect across speakers of 25 languages representing nine language families and 10 writing systems. Overall, we found strong evidence for the effect across languages, with bouba eliciting more congruent responses than kiki. Participants who spoke languages with Roman scripts were only marginally more likely to show the effect, and analysis of the orthographic shape of the words in different scripts showed that the effect was no stronger for scripts that use rounder forms for bouba and spikier forms for kiki. These results confirm that the bouba/kiki phenomenon is rooted in crossmodal correspondence between aspects of the voice and visual shape, largely independent of orthography. They provide the strongest demonstration to date that the bouba/kiki effect is robust across cultures and writing systems. This article is part of the theme issue 'Voice modulation: from origin and mechanism to social impact (Part II)'.

Development and validation of combined symptom‐medication scores for allergic rhinitis*

Abstract: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs.We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air® , and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]).We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820).The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.

All things retarded: radiation-reaction in worldline quantum field theory

Abstract: A bstract We exhibit an initial-value formulation of the worldline quantum field theory (WQFT) approach to the classical two-body problem in general relativity. We show that the Schwinger-Keldysh (in-in) formalism leads to purely retarded propagators in the evaluation of observables in the WQFT. Integration technology for retarded master integrals is introduced at third post-Minkowskian (3PM) order. As an application we compute the complete radiation-reacted impulse and radiated four momentum for the scattering of two non-spinning neutron stars including tidal effects at 3PM order, as well as the leading (2PM) far-field gravitational waveform.

Impact of Anthropomorphic Robot Design on Trust and Attention in Industrial Human-Robot Interaction

Abstract: The application of anthropomorphic features to robots is generally considered beneficial for human-robot interaction (HRI). Although previous research has mainly focused on social robots, the pheno...

Electronic properties of metal halide perovskites and their interfaces: the basics.

Abstract: We have witnessed tremendous progress of metal halide perovskite (MHP)-based optoelectronic devices, especially in the field of photovoltaics. Despite intensive research in the past few years, questions still remain regarding their fundamental optoelectronic properties, among which the electronic properties exhibit an interplay of numerous phenomena that deserve serious scrutiny. In this Focus article, we aim to provide a contemporary understanding of the unique electronic properties that has been resolved by the community. First introducing some of the basic concepts established in semiconductor physics, the intrinsic and extrinsic electronic properties of the MHPs are disentangled and explained. With this, the complex interplay of interface-, dopant-, and surface state-induced electronic states in determining the electrostatic landscape in the material can be comprehended, and the energy level alignment in device architectures more reliably assessed.

Evolutionary Impact of Size-Selective Harvesting on Shoaling Behavior: Individual-Level Mechanisms and Possible Consequences for Natural and Fishing Mortality

Abstract: AbstractIntensive and size-selective harvesting is an evolutionary driver of life history as well as individual behavioral traits. Yet whether and to what degree harvesting modifies the collective behavior of exploited species are largely unknown. We present a multigeneration harvest selection experiment with zebrafish, Danio rerio, as a model species to understand the effects of size-selective harvesting on shoaling behavior. The experimental system is based on a large-harvested (typical of most wild-capture fisheries targeting larger size classes) and small-harvested (typical of specialized fisheries and gape-limited predators targeting smaller size classes) selection lines. By combining high-resolution tracking of fish behavior with computational agent-based modeling, we show that shoal cohesion changed in the direction expected by a trade-off between individual vigilance and the use of social cues. In particular, we document a decrease of individual vigilance in the small-harvested line, which was linked to an increase in the attention to social cues, favoring more cohesive shoals. Opposing outcomes were found for the large-harvested line, which formed less cohesive shoals. Using the agent-based model, we outline possible consequences of changes in shoaling behavior for both fishing and natural mortality. The changes in shoaling induced by large size-selective harvesting may decrease fishing mortality but increase mortality by natural predators. Our work suggests an insofar overlooked evolutionary mechanism by which size-selective harvesting can affect fishing and natural mortality of exploited fish.

Coping with COVID: risk and resilience factors for mental health in a German representative panel study

Abstract: The coronavirus disease 2019 (COVID-19) pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare.In a stratified random sample of the German household population (n = 6684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress [(PD; measured via Patient Health Questionnaire for Depression and Anxiety (PHQ-4)] from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting.PHQ-4 scores in 2020 (M = 2.45) and 2021 (M = 2.21) were elevated compared to 2019 (M = 1.79). Several risk factors (catastrophizing, neuroticism, and asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, and optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes.We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. A comparison of pre-pandemic data stresses the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.

Natural History of Obesity Due to POMC, PCSK1, and LEPR Deficiency and the Impact of Setmelanotide

Abstract: Rare homozygous or biallelic variants in POMC, PCSK1, and LEPR can disrupt signaling through the melanocortin-4 receptor (MC4R) pathway, resulting in hyperphagia and severe early-onset obesity. In pivotal Phase 3 clinical trials, treatment with the MC4R agonist setmelanotide reduced hunger and weight in patients with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency.To characterize the historical weight trajectory in these patients.This analysis included data from 2 pivotal single-arm, open-label, Phase 3 trials (NCT02896192, NCT03287960). These were multicenter trials. Patients had obesity due to POMC/PCSK1 or LEPR deficiency. During the trial, patients were treated with setmelanotide. Historical data on measured weight and height were obtained during screening.A total of 17 patients (POMC, n = 8; PCSK1, n = 1; LEPR, n = 8) with historical weight and height data were included in this analysis. Before setmelanotide treatment, patients with obesity due to POMC/PCSK1 or LEPR deficiency were above the 95th percentile for weight throughout childhood, demonstrated continuous weight gain, and did not show long-term weight loss upon interventions (eg, diet, surgery, exercise). Setmelanotide treatment attenuated weight and body mass index trajectories over the observation period of 1 year.In patients with POMC, PCSK1, or LEPR deficiency, traditional interventions for weight loss had limited impact on the trajectory of severe early-onset obesity. However, setmelanotide treatment attenuated weight and body mass index trajectories and led to weight loss associated with health benefits in most individuals.