Recent Additions

  • Publication
    A Core Outcome Set for Efficacy of Acute Treatment of Hereditary Angioedema
    ( 2024)
    Petersen, Remy S.
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    Fijen, Lauré
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    Apfelbacher, Christian
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    Magerl, Markus
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    Weller, Karsten
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    Aberer, Werner
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    Adatia, Adil
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    Audhya, Paul
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    Bara N.A., Noémi-Anna
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    Betschel, Stephen
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    Boccon-Gibod, Isabelle
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    Bouillet, Laurence
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    Brodszki, Nicholas
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    Busse, Paula J.
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    Buttgereit, Thomas
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    Bygum, Anette
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    Cancian, Mauro
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    Craig, Timothy
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    Csuka, Dorottya
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    Farkas, Henriette
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    Fomina, Daria
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    Gil-Serrano, Johana
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    Gompels, Mark
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    Guidos Fogelbach, Guillermo
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    Guilarte, Mar
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    Hide, Michihiro
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    Kiani-Alikhan, Sorena
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    Kinaciyan, Tamar
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    Lenten, Annet
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    lleonart, Ramon
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    Longhurst, Hilary
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    Lumry, William R.
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    Malbran, Alejandro
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    Malinauskiene, Laura
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    Matta Campos, Juan J.
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    Mendivil, Joan
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    Nieto-Martinez, Sandra A.
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    Peter, Jonathan G.
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    Porebski, Grzegorz
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    Reshef, Avner
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    Riedl, Marc
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    Valerieva, Anna
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    Waserman, Susan
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    Maurer, Marcus
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    Cohn, Danny M.
    Background: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants. Objective: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks. Methods: We conducted a Delphi consensus study involving all relevant parties: patients with hereditary angioedema, hereditary angioedema expert clinicians and clinical researchers, pharmaceutical companies, and regulatory bodies. Two Internet-based survey rounds were conducted. In round 1, panelists indicated the importance of individual outcomes used in clinical trials on a 9-point Likert scale. Based on these results, a core outcome set was developed and voted on by panelists in round 2. Results: A total of 58 worldwide panelists completed both rounds. The first round demonstrated high importance scores and substantial agreement among the panelists. In the second round, a consensus of 90% or greater was achieved on a core outcome set consisting of five key outcomes: change in overall symptom severity at one predetermined time point between 15 minutes and 4 hours after treatment, time to end of progression of all symptoms, the need for rescue medication during the entire attack, impairment of daily activities, and treatment satisfaction. Conclusions: This international study obtained a high level of consensus on a core outcome set for the acute treatment of hereditary angioedema attacks, consisting of five key outcomes.
  • Publication
    Bimekizumab treatment in patients with active psoriatic arthritis and prior inadequate response to tumour necrosis factor inhibitors: 52-week safety and efficacy from the phase III BE COMPLETE study and its open-label extension BE VITAL
    ( 2024)
    Coates, Laura C.
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    Landewé, Robert
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    McInnes, Iain B.
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    Mease, Phillip J.
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    Ritchlin, Christopher T.
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    Tanaka, Yoshiya
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    Asahina, Akihiko
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    Behrens, Frank
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    Gladman, Dafna D.
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    Gossec, Laure
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    Orbai, Ana-Maria
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    Gottlieb, Alice B.
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    Warren, Richard B.
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    Ink, Barbara
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    Bajracharya, Rajan
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    Shende, Vishvesh
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    Coarse, Jason
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    Merola, Joseph F.
    Objectives To assess 52-week safety and efficacy of bimekizumab in patients with active psoriatic arthritis (PsA) and prior inadequate response/intolerance to tumour necrosis factor inhibitors. Methods Patients completing the 16-week phase III double-blind, placebo-controlled BE COMPLETE (NCT03896581) study entered the open-label extension, BE VITAL (NCT04009499). All patients in BE VITAL received 160 mg bimekizumab every 4 weeks. Safety and efficacy are reported to week 52. Results A total of 347/400 (86.8%) patients completed week 52. To week 52, the exposure-adjusted incidence rate/100 patient-years for ≥1 treatment-emergent adverse event (TEAE) was 126.0, and was 7.0 for serious TEAEs. The most frequent TEAEs were SARSCoV-2 (COVID-19), oral candidiasis, nasopharyngitis and urinary tract infection. All fungal infections were mild or moderate in severity and localised; two patients discontinued the study due to oral candidiasis. No cases of active tuberculosis, uveitis or inflammatory bowel disease were reported. One sudden death occurred. Sustained efficacy was observed with bimekizumab from week 16 to 52 across clinical and patient-reported outcomes. At week 52, 51.7% bimekizumab-randomised and 40.6% placebo/bimekizumab patients (receiving bimekizumab from week 16 to 52) had ≥50% improvement in the American College of Rheumatology criteria. Complete skin clearance (Psoriasis Area and Severity Index 100) was achieved by 65.9% bimekizumab and 60.2% placebo/bimekizumab patients at week 52. Minimal disease activity was achieved by 47.2% bimekizumab and 33.1% placebo/bimekizumab patients at week 52. Conclusions Bimekizumab demonstrated a safety profile consistent with previous reports; no new safety signals were identified. Sustained efficacy was observed from week 16 to 52.
  • Publication
    Immune signatures of checkpoint inhibitor-induced autoimmunity - A focus on neurotoxicity
    ( 2024)
    Müller-Jensen, Leonie
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    Schulz, Axel R.
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    Mei, Henrik E.
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    Mohr, Raphael
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    Ulrich, Claas
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    Knape, Philipp
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    Frost, Nikolaj
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    Frischbutter, Stefan
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    Kunkel, Desiree
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    Schinke, Christian
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    Ginesta Roque, Lorena
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    Maierhof, Smilla K.
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    Nickel, Florian T.
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    Heinzerling, Lucie
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    Endres, Matthias
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    Boehmerle, Wolfgang
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    Huehnchen, Petra
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    Knauss, Samuel
    Background: Neurologic immune-related adverse events (irAE-n) are rare but severe toxicities of immune checkpoint inhibitor (ICI) treatment. To overcome diagnostic and therapeutic challenges, a better mechanistic understanding of irAE-n is paramount. Methods: In this observational cohort study, we collected serum and peripheral blood samples from 34 consecutive cancer patients with irAE-n (during acute illness) and 49 cancer control patients without irAE-n (pre- and on-ICI treatment, n = 44 without high-grade irAEs, n = 5 with high-grade nonneurologic irAEs). Patients received either anti-programmed cell death protein (PD)-1 or anti-PD ligand-1 monotherapy or anti-PD-1/anti-cytotoxic T-lymphocyte-associated protein-4 combination therapy. Most common cancers were melanoma, lung cancer, and hepatocellular carcinoma. Peripheral blood immune profiling was performed using 48-marker single-cell mass cytometry and a multiplex cytokine assay. Results: During acute illness, patients with irAE-n presented higher frequencies of cluster of differentiation (CD)8+ effector memory type (EM-)1 and central memory (CM) T cells compared to controls without irAEs. Multiorgan immunotoxicities (neurologic + nonneurologic) were associated with higher CD8+ EM1 T cell counts. While there were no B cell changes in the overall cohort, we detected a marked decrease of IgD- CD11c+ CD21low and IgD- CD24+ CD21high B cells in a subgroup of patients with autoantibody-positive irAE-n. We further identified signatures indicative of enhanced chemotaxis and inflammation in irAE-n patients and discovered C-X-C motif chemokine ligand (CXCL)10 as a promising marker to diagnose high-grade immunotoxicities such as irAE-n. Conclusions: We demonstrate profound and partly subgroup-specific immune cell dysregulation in irAE-n patients, which may guide future biomarker development and targeted treatment approaches.
  • Publication
    Nociceptive Processing of Elite Athletes Varies between Sport-Specific Loads: An EEG-Based Study Approach
    ( 2024)
    Dreismickenbecker, Elias
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    Fleckenstein, Johannes
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    Walter, Carmen
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    Enax-Krumova, Elena K.
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    Fischer, Michael J. M.
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    Kreuzer, Matthias
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    Anders, Malte
    Introduction For the downstream nociceptive processing of elite athletes, recent studies indicate that athletes probably tolerate more pain as compared with a normally active population. Phenotyping the nociceptive processing of athletes in different types of endurance sports can provide insight into training-specific effects, which may help in understanding the long-term effects of specific exercise. Methods Twenty-six elite endurance athletes from the disciplines of rowing, triathlon, and running and 26 age- and sex-matched, recreationally active control subjects who participated in the subjective pain perception and processing of standardized noxious stimuli were investigated by EEG. This included standardized heat pain thresholds (HPT) and contact heat-evoked potentials from heat stimulation, measured with EEG as well as pinprick-evoked potentials from mechanical stimulation. Results After noxious stimulation, athletes showed a higher activation of the event-related spectral perturbation (ERSP) patterns in the N2P2 EEG response at the Cz Electrode compared with the controls. After noxious contact heat stimulation, triathletes had a higher ERSP activation compared with the controls, whereas the rowers had a higher ERSP activation after noxious mechanical stimulation. Also, HPT in triathletes were increased despite their increased central activation after thermal stimulation. We found a correlation between increased HPT and training hours and years, although athletes did not differ within these variables. Conclusions Although we were able to identify differences between athletes of different endurance sports, the reasons and implications of these differences remain unclear. The study of sport-specific somatosensory profiles may help to understand the mechanisms of exercise-related long-term effects on pain processing and perception. Furthermore, sport-specific somatosensory effects may support the personalization of exercise interventions and identify risk factors for chronic pain in elite athletes.
  • Publication
    Structural basis for the bi-specificity of USP25 and USP28 inhibitors
    ( 2024)
    Patzke, Jonathan Vincent
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    Sauer, Florian
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    Nair, Radhika Karal
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    Endres, Erik
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    Proschak, Eugen
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    Hernández Olmos, Víctor
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    Sotriffer, Christoph
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    Kisker, Caroline
    The development of cancer therapeutics is often hindered by the fact that specific oncogenes cannot be directly pharmaceutically addressed. Targeting deubiquitylases that stabilize these oncogenes provides a promising alternative. USP28 and USP25 have been identified as such target deubiquitylases, and several small-molecule inhibitors indiscriminately inhibiting both enzymes have been developed. To obtain insights into their mode of inhibition, we structurally and functionally characterized USP28 in the presence of the three different inhibitors AZ1, Vismodegib and FT206. The compounds bind into a common pocket acting as a molecular sink. Our analysis provides an explanation why the two enzymes are inhibited with similar potency while other deubiquitylases are not affected. Furthermore, a key glutamate residue at position 366/373 in USP28/USP25 plays a central structural role for pocket stability and thereby for inhibition and activity. Obstructing the inhibitor-binding pocket by mutation of this glutamate may provide a tool to accelerate future drug development efforts for selective inhibitors of either USP28 or USP25 targeting distinct binding pockets.

Most viewed

  • Publication
    Quanten-Ghost-Imaging mit asynchroner Detektion
    Ein fortschrittlicher Aufbau für Quanten-Ghost-Imaging ermöglicht rauscharme 3-D-Bildgebung von entfernten Objekten. Eine wesentliche technische Neuerung liegt in der asynchronen Detektion durch unabhängige SPAD-Detektoren, wodurch sich der Aufbau entscheidend vereinfachen lässt und sich nun für beliebige Entfernungen eignet. Wie jüngste experimentelle Ergebnisse verdeutlichen, besitzt dieser Aufbau das Potenzial, klassische Systeme in vielen Aspekten zu übertreffen.
  • Publication
    Ready or Not, AI Comes - an Interview Study of Organizational AI Readiness Factors
    ( 2021)
    Jöhnk, J.
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    Weißert, M.
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    Wyrtki, K.
    Artificial intelligence (AI) offers organizations much potential. Considering the manifold application areas, AI's inherent complexity, and new organizational necessities, companies encounter pitfalls when adopting AI. An informed decision regarding an organization's readiness increases the probability of successful AI adoption and is important to successfully leverage AI's business value. Thus, companies need to assess whether their assets, capabilities, and commitment are ready for the individual AI adoption purpose. Research on AI readiness and AI adoption is still in its infancy. Consequently, researchers and practitioners lack guidance on the adoption of AI. The paper presents five categories of AI readiness factors and their illustrative actionable indicators. The AI readiness factors are deduced from an in-depth interview study with 25 AI experts and triangulated with both scientific and practitioner literature. Thus, the paper provides a sound set of organizational AI readiness factors, derives corresponding indicators for AI readiness assessments, and discusses the general implications for AI adoption. This is a first step toward conceptualizing relevant organizational AI readiness factors and guiding purposeful decisions in the entire AI adoption process for both research and practice.
  • Publication
    Lamellierte Aktiv-Werkzeugelemente in flexiblen Blechumformwerkzeugen
    ( 1999)
    Garreis, F.
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    Geiger, M.
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    Euringer, M.
    By the acquired CAD/CAM-process chain, which includes the lamination of activ-elements and generation of NC-programs, work planning for manufacturing of laminated activ-elements can be simplified significantly. By optimization of seam length, seam arrangement and weld cycle nondeforming lamella-blocks can be fabricated by laser beam welding. Postprocessing of weld camber by polishing is necessary.
  • Publication
    Einfluß variabler Designeffekte auf den Wirkungsgrad von seriell verschalteten Farbstoffsolarmodulen
    ( 2006)
    Brandt, Henning
    Diplomarbeit im an der Fachhochschule für Technik und Wirtschaft Berlin, Studiengang: Umwelttechnik / Regenerative Energien. Angefertigt am Fraunhofer-Institut für Solare Energiesysteme Freiburg (ISE).
  • Publication
    BMP-2 (and partially GDF-5) coating significantly accelerates and augments bone formation close to hydroxyapatite/tricalcium-phosphate/brushite implant cylinders for tibial bone defects in senile, osteopenic sheep
    ( 2023)
    Sachse, André
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    Hasenbein, Ines
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    Hortschansky, Peter
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    Schmuck, Klaus D.
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    Maenz, Stefan
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    Illerhaus, Bernhard
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    ; ;
    Huber, Rene
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    Kunisch, Elke
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    Horbert, Victoria
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    Gunnella, Francesca
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    Roth, Andreas J.
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    Schubert, Harald
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    Kinne, Raimund W.
    Bilateral defects (diameter 8 mm) in the medial tibial head of senile, osteopenic female sheep (n = 48; 9.63 ± 0.10 years; mean ± SEM) were treated with hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP)/dicalcium phosphate dihydrate (DCPD; brushite) cylinders coated with BMP-2 (25 or 250 micrograms) or growth differentiation factor (GDF)-5 (125 or 1250 micrograms; left side); cylinders without BMP served as controls (right side). Three, 6, and 9 months post-operation (n = 6 each group), bone structure and formation were analyzed in vivo by X-ray and ex vivo by osteodensitometry, histomorphometry, and micro-computed tomography (micro-CT) at 3 and 9 months. Semi-quantitative X-ray evaluation showed significantly increasing bone densities around all implant cylinders over time. High-dose BMP-2-coated cylinders (3 and 9 months) and low-dose GDF-5-coated cylinders (3 and 6 months) demonstrated significantly higher densities than controls (dose-dependent for BMP-2 at 3 months). This was confirmed by osteodensitometry at 9 months for high-dose BMP-2-coated cylinders (and selected GDF-5 groups), and was again dose-dependent for BMP-2. Osteoinduction by BMP-2 was most pronounced in the adjacent bone marrow (dynamic histomorphometry/micro-CT). BMP-2 (and partially GDF-5) significantly increased the bone formation in the vicinity of HA/TCP/DCPD cylinders used to fill tibial bone defects in senile osteopenic sheep and may be suitable for surgical therapy of critical size, non-load-bearing bone defects in cases of failed tibial head fracture or defect healing.