TY - JOUR A1 - Baumbach, Sebastian Felix A1 - Hörterer, Hubert A1 - Oppelt, Sonja A1 - Szeimies, Ulrike A1 - Polzer, Hans A1 - Walther, Markus T1 - Do pre-operative radiologic assessment predict postoperative outcomes in patients with insertional Achilles tendinopathy?: a retrospective database study JF - Archives of Orthopaedic and Trauma Surgery N2 - Introduction Diagnosis and treatment of insertional tendinopathy of the Achilles tendon (IAT) remains a challenge. The aim of this study was to assess the influence of pre-operative radiological pathologies on the patient-reported outcomes following open debridement of all pathologies for IAT. Materials and methods In this IRB-approved retrospective correlation and comparative study, patients with pre-operative imaging were identified from the authors’ retrospective IAT database comprising of 118 patients. All were treated by a standardized surgical treatment strategy utilizing a midline, transachillary approach and debridement of all pathologies. A total of fifteen radiologic parameters were measured on radiographs (RX) and MRI. The patient-reported outcomes were assessed using the Victorian Institute of Sport Assessment-Achilles questionnaire (VISA-A-G) and the general health questionnaire SF-12 at a minimum follow-up of 12 months. The data are presented as mean ± SD (95% CI). Results 88 patients (74.6%) with an average age of 50 ± 12 (47–52) years were included. Radiographs were available in 68 patients and MRI in 53. The mean follow-up was 3.8 ± 1.9 (3.4–4.3) years. The overall VISA-A-G was 81 ± 22 (77–86), the SF-12 PCS 54 ± 7 (52–55), and the SF-12 MCS 52 ± 9 (50–54) points. None of the assessed radiological parameters had a significant influence on the patient-reported outcome following surgical treatment for IAT. Conclusion In this retrospective correlation study, no significant association was found between preoperative radiographic and MRI radiologic parameters for IAT and postoperative patient-reported outcomes (VISA-A-G and SF-12). KW - Achilles KW - insertion KW - PROM KW - imaging KW - surgery Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307963 SN - 1434-3916 VL - 142 IS - 11 ER - TY - JOUR A1 - Kraemer, Markus A1 - Becker, Jana A1 - Bley, Thorsten Alexander A1 - Steinbrecher, Andreas A1 - Minnerup, Jens A1 - Hellmich, Bernhard T1 - Diagnostik und Therapie der Riesenzellarteriitis T1 - Diagnostics and treatment of giant cell arteritis JF - Der Nervenarzt N2 - Die Riesenzellarteriitis (RZA) ist in der Altersgruppe der über 50-Jährigen die häufigste idiopathische systemische Vaskulitis. Die Erkrankung bedarf einer zeitnahen Diagnostik und Therapie, um schwere Komplikationen wie eine Erblindung oder einen Schlaganfall zu vermeiden. Die Rezidivneigung erfordert eine mehrjährige, zum Teil lebenslange Glukokortikoid(GC)-Therapie, was das Risiko GC-induzierter Langzeitnebenwirkungen erhöht. Daher wird bei der Mehrzahl der Patienten eine additive GC-einsparende Therapie empfohlen. Hierzu steht der Anti-IL-6-Rezeptor-Antikörper Tocilizumab in subkutaner Applikation als zugelassene Substanz zur Verfügung, alternativ kann Methotrexat (MTX) eingesetzt werden (off-label). N2 - Giant cell arteritis (GCA) is the most common idiopathic systemic vasculitis in the age group over 50 years. It requires prompt diagnostics and treatment to avoid severe complications, such as visual loss or stroke. The tendency to relapse makes a glucocorticoid (GC) treatment necessary for several years and sometimes lifelong, which increases the risk of GC-induced long-term side effects. Therefore, additive GC-sparing treatment is recommended in the majority of patients. For this purpose, the anti-IL‑6 receptor antibody tocilizumab is available as an approved substance for subcutaneous application; alternatively, methotrexate (MTX) can be used (off-label). KW - Riesenzellarteriitis KW - Diagnose KW - Therapie KW - Glukokortikoide KW - Glukokortikoideinsparende Therapie KW - Tocilizumab KW - Methotrexat KW - giant cell arteritis KW - diagnosis KW - therapy KW - glucocorticoids KW - glucocorticoid-sparing agents KW - Tocilizumab KW - Methotrexate Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307771 SN - 0028-2804 SN - 1433-0407 VL - 93 IS - 8 ER - TY - JOUR A1 - Gschmack, Eva A1 - Monoranu, Camelia-Maria A1 - Marouf, Hecham A1 - Meyer, Sarah A1 - Lessel, Lena A1 - Idris, Raja A1 - Berg, Daniela A1 - Maetzler, Walter A1 - Steigerwald, Frank A1 - Volkmann, Jens A1 - Gerlach, Manfred A1 - Riederer, Peter A1 - Koutsilieri, Eleni A1 - Scheller, Carsten T1 - Plasma autoantibodies to glial fibrillary acidic protein (GFAP) react with brain areas according to Braak staging of Parkinson’s disease JF - Journal of Neural Transmission N2 - Idiopathic Parkinson’s disease (PD) is characterized by a progredient degeneration of the brain, starting at deep subcortical areas such as the dorsal motor nucleus of the glossopharyngeal and vagal nerves (DM) (stage 1), followed by the coeruleus–subcoeruleus complex; (stage 2), the substantia nigra (SN) (stage 3), the anteromedial temporal mesocortex (MC) (stage 4), high-order sensory association areas and prefrontal fields (HC) (stage 5) and finally first-order sensory association areas, premotor areas, as well as primary sensory and motor field (FC) (stage 6). Autoimmunity might play a role in PD pathogenesis. Here we analyzed whether anti-brain autoantibodies differentially recognize different human brain areas and identified autoantigens that correlate with the above-described dissemination of PD pathology in the brain. Brain tissue was obtained from deceased individuals with no history of neurological or psychiatric disease and no neuropathological abnormalities. Tissue homogenates from different brain regions (DM, SN, MC, HC, FC) were subjected to SDS-PAGE and Western blot. Blots were incubated with plasma samples from 30 PD patients and 30 control subjects and stained with anti-IgG antibodies to detect anti-brain autoantibodies. Signals were quantified. Prominent autoantigens were identified by 2D-gel-coupled mass spectrometry sequencing. Anti-brain autoantibodies are frequent and occur both in healthy controls and individuals with PD. Glial fibrillary acidic protein (GFAP) was identified as a prominent autoantigen recognized in all plasma samples. GFAP immunoreactivity was highest in DM areas and lowest in FC areas with no significant differences in anti-GFAP autoantibody titers between healthy controls and individuals with PD. The anti-GFAP autoimmunoreactivity of different brain areas correlates with the dissemination of histopathological neurodegeneration in PD. We hypothesize that GFAP autoantibodies are physiological but might be involved as a cofactor in PD pathogenesis secondary to a leakage of the blood–brain barrier. KW - Parkinson KW - GFAP KW - autoantibodies KW - Braak Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325161 VL - 129 IS - 5-6 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Weinzierl, Franz-Xaver A1 - Buck, Andreas K. A1 - Rowe, Steven P. A1 - Higuchi, Takahiro A1 - Seitz, Anna Katharina A1 - Kübler, Hubert A1 - Schirbel, Andreas A1 - Essler, Markus A1 - Bundschuh, Ralph A. A1 - Werner, Rudolf A. T1 - Matched-pair analysis of [\(^{177}\)Lu]Lu-PSMA I&T and [\(^{177}\)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - Background Labelled with lutetium-177, the urea-based small molecules PSMA I&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT. Materials and methods A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [\(^{177}\)Lu]Lu-PSMA I&T, and a matched cohort of 55 patients treated with [\(^{177}\)Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared. Results Toxicity assessment revealed grade III anaemia in a single patient (1.8%) for [\(^{177}\)Lu]Lu-PSMA I&T and five (9.1%) for [\(^{177}\)Lu]Lu-PSMA-617. In addition, one (1.9%) grade III thrombopenia for [\(^{177}\)Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [\(^{177}\)Lu]Lu-PSMA I&T did not differ significantly when compared to patients treated with [\(^{177}\)Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). Conclusion In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed. KW - PSMA I&T KW - PSMA-617 KW - prostate-specific membrane antigen KW - prostate cancer KW - radioligand therapy KW - matched pair Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324581 VL - 49 IS - 9 ER - TY - JOUR A1 - Kuon, Jonas A1 - Blasi, Miriam A1 - Unsöld, Laura A1 - Vogt, Jeannette A1 - Mehnert, Anja A1 - Alt-Epping, Bernd A1 - Oorschot, Birgitt van A1 - Sistermanns, Jochen A1 - Ahlborn, Miriam A1 - Ritterbusch, Ulrike A1 - Stevens, Susanne A1 - Kahl, Christoph A1 - Ruellan, Anne A1 - Matthias, Kathrin A1 - Kubin, Thomas A1 - Stahlhut, Kerstin A1 - Heider, Andrea A1 - Lordick, Florian A1 - Thomas, Michael T1 - Impact of molecular alterations on quality of life and prognostic understanding over time in patients with incurable lung cancer: a multicenter, longitudinal, prospective cohort study JF - Supportive Care in Cancer N2 - Purpose The purpose of this study is to investigate changes over time in quality of life (QoL) in incurable lung cancer patients and the impact of determinants like molecular alterations (MA). Methods In a prospective, longitudinal, multicentric study, we assessed QoL, symptom burden, psychological distress, unmet needs, and prognostic understanding of patients diagnosed with incurable lung cancer at the time of the diagnosis (T0) and after 3 (T1), 6 (T2) and 12 months (T3) using validated questionnaires like FACT-L, National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT), PHQ-4, SCNS-SF-34, and SEIQoL. Results Two hundred seventeen patients were enrolled, 22 (10%) with reported MA. QoL scores improved over time, with a significant trend for DT, PHQ-4, and SCNS-SF-34. Significant determinants for stable or improving scores over time were survival > 6 months, performance status at the time of diagnosis, and presence of MA. Patients with MA showed better QoL scores (FACT-L at T1 104.4 vs 86.3; at T2 107.5 vs 90.0; at T3 100.9 vs 92.8) and lower psychological distress (NCCN DT at T1 3.3 vs 5; at T2 2.7 vs 4.5; at T3 3.7 vs 4.5; PHQ-4 at T1 2.3 vs 4.1; at T2 1.7 vs 3.6; at T3 2.2 vs 3.6), but also a worsening of the scores at 1 year and a higher percentage of inaccurate prognostic understanding (27 vs 17%) compared to patients without MA. Conclusion Patients with tumors harboring MA are at risk of QoL deterioration during the course of the disease. Physicians should adapt their communication strategies in order to maintain or improve QoL. KW - lung cancer KW - quality of life KW - molecular alterations KW - prognostic awareness Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308211 SN - 0941-4355 SN - 1433-7339 VL - 30 IS - 4 ER - TY - JOUR A1 - Bernhard, Lukas A1 - Krumpholz, Roman A1 - Krieger, Yannick A1 - Czempiel, Tobias A1 - Meining, Alexander A1 - Navab, Nassir A1 - Lüth, Tim A1 - Wilhelm, Dirk T1 - PLAFOKON: a new concept for a patient-individual and intervention-specific flexible surgical platform JF - Surgical Endoscopy N2 - Background Research in the field of surgery is mainly driven by aiming for trauma reduction as well as for personalized treatment concepts. Beyond laparoscopy, other proposed approaches for further reduction of the therapeutic trauma have failed to achieve clinical translation, with few notable exceptions. We believe that this is mainly due to a lack of flexibility and high associated costs. We aimed at addressing these issues by developing a novel minimally invasive operating platform and a preoperative design workflow for patient-individual adaptation and cost-effective rapid manufacturing of surgical manipulators. In this article, we report on the first in-vitro cholecystectomy performed with our operating platform. Methods The single-port overtube (SPOT) is a snake-like surgical manipulator for minimally invasive interventions. The system layout is highly flexible and can be adapted in design and dimensions for different kinds of surgery, based on patient- and disease-specific parameters. For collecting and analyzing this data, we developed a graphical user interface, which assists clinicians during the preoperative planning phase. Other major components of our operating platform include an instrument management system and a non-sterile user interface. For the trial surgery, we used a validated phantom which was further equipped with a porcine liver including the gallbladder. Results Following our envisioned preoperative design workflow, a suitable geometry of the surgical manipulator was determined for our trial surgery and rapidly manufactured by means of 3D printing. With this setup, we successfully performed a first in-vitro cholecystectomy, which was completed in 78 min. Conclusions By conducting the trial surgery, we demonstrated the effectiveness of our PLAFOKON operating platform. While some aspects – especially regarding usability and ergonomics – can be further optimized, the overall performance of the system is highly promising, with sufficient flexibility and strength for conducting the necessary tissue manipulations. KW - individualized surgery KW - surgical manipulator KW - operating platform KW - preoperative planning KW - 3D printing Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307490 SN - 0930-2794 SN - 1432-2218 VL - 36 IS - 7 ER - TY - JOUR A1 - Dietzsch, Stefan A1 - Braesigk, Annett A1 - Seidel, Clemens A1 - Remmele, Julia A1 - Kitzing, Ralf A1 - Schlender, Tina A1 - Mynarek, Martin A1 - Geismar, Dirk A1 - Jablonska, Karolina A1 - Schwarz, Rudolf A1 - Pazos, Montserrat A1 - Weber, Damien C. A1 - Frick, Silke A1 - Gurtner, Kristin A1 - Matuschek, Christiane A1 - Harrabi, Semi Ben A1 - Glück, Albrecht A1 - Lewitzki, Victor A1 - Dieckmann, Karin A1 - Benesch, Martin A1 - Gerber, Nicolas U. A1 - Obrecht, Denise A1 - Rutkowski, Stefan A1 - Timmermann, Beate A1 - Kortmann, Rolf-Dieter T1 - Types of deviation and review criteria in pretreatment central quality control of tumor bed boost in medulloblastoma—an analysis of the German Radiotherapy Quality Control Panel in the SIOP PNET5 MB trial JF - Strahlentherapie und Onkologie N2 - Purpose In Germany, Austria, and Switzerland, pretreatment radiotherapy quality control (RT-QC) for tumor bed boost (TB) in non-metastatic medulloblastoma (MB) was not mandatory but was recommended for patients enrolled in the SIOP PNET5 MB trial between 2014 and 2018. This individual case review (ICR) analysis aimed to evaluate types of deviations in the initial plan proposals and develop uniform review criteria for TB boost. Patients and methods A total of 78 patients were registered in this trial, of whom a subgroup of 65 patients were available for evaluation of the TB treatment plans. Dose uniformity was evaluated according to the definitions of the protocol. Additional RT-QC criteria for standardized review of target contours were elaborated and data evaluated accordingly. Results Of 65 initial TB plan proposals, 27 (41.5%) revealed deviations of target volume delineation. Deviations according to the dose uniformity criteria were present in 14 (21.5%) TB plans. In 25 (38.5%) cases a modification of the RT plan was recommended. Rejection of the TB plans was rather related to unacceptable target volume delineation than to insufficient dose uniformity. Conclusion In this analysis of pretreatment RT-QC, protocol deviations were present in a high proportion of initial TB plan proposals. These findings emphasize the importance of pretreatment RT-QC in clinical trials for MB. Based on these data, a proposal for RT-QC criteria for tumor bed boost in non-metastatic MB was developed. KW - brain tumor KW - pediatric KW - focal radiotherapy KW - quality assurance KW - individual case review Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307812 SN - 0179-7158 SN - 1439-099X VL - 198 IS - 3 ER - TY - JOUR A1 - Dürrnagel, Matteo A1 - Beyer, Jacob A1 - Thomale, Ronny A1 - Schwemmer, Tilman T1 - Unconventional superconductivity from weak coupling JF - The European Physical Journal B N2 - We develop a joint formalism and numerical framework for analyzing the superconducting instability of metals from a weak coupling perspective. This encompasses the Kohn–Luttinger formulation of weak coupling renormalization group for superconductivity as well as the random phase approximation imposed on the diagrammatic expansion of the two-particle Green’s function. The central quantity to resolve is the effective interaction in the Cooper channel, for which we develop an optimized numerical framework. Our code is capable of treating generic multi-orbital models in two as well as three spatial dimensions and, in particular, arbitrary avenues of spin-orbit coupling. KW - superconducting instability KW - metals KW - weak coupling KW - unconventional superconductivity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325153 SN - 1434-6028 VL - 95 IS - 7 ER - TY - JOUR A1 - Kourou, Maria A1 - Zarvalis, Konstantinos T1 - Compact sets in petals and their backward orbits under semigroups of holomorphic functions JF - Potential Analysis N2 - Let (ϕ\(_t\))\(_{t≥0}\) be a semigroup of holomorphic functions in the unit disk \(\mathbb {D}\) and K a compact subset of \(\mathbb {D}\). We investigate the conditions under which the backward orbit of K under the semigroup exists. Subsequently, the geometric characteristics, as well as, potential theoretic quantities for the backward orbit of K are examined. More specifically, results are obtained concerning the asymptotic behavior of its hyperbolic area and diameter, the harmonic measure and the capacity of the condenser that K forms with the unit disk. KW - semigroup of holomorphic functions KW - backward orbit KW - petal KW - harmonic measure KW - condenser capacity KW - Koenigs function KW - green energy KW - hyperbolic area Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324368 SN - 0926-2601 VL - 59 IS - 4 ER - TY - JOUR A1 - Franz, David J. T1 - Moral responsibility for self-deluding beings JF - Philosophia N2 - In this article, I argue for four theses. First, libertarian and compatibilist accounts of moral responsibility agree that the capability of practical reason is the central feature of moral responsibility. Second, this viewpoint leads to a reasons-focused account of human behavior. Examples of human action discussed in debates about moral responsibility suggest that typical human actions are driven primarily by the agent’s subjective reasons and are sufficiently transparent for the agent. Third, this conception of self-transparent action is a questionable idealization. As shown by psychological research on self-assessment, motivated reasoning, and terror management theory, humans oftentimes have only a limited understanding of their conduct. Self-deception is rather the rule than the exception. Fourth, taking the limited self-transparency of practical reason seriously leads to a socially contextualized conception of moral responsibility. KW - moral responsibility KW - self-deception KW - reasoning biases KW - practical reasoning KW - rationalization KW - motivated reasoning Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324871 SN - 0048-3893 VL - 50 IS - 4 ER - TY - JOUR A1 - Beyer, Jacob A1 - Goth, Florian A1 - Müller, Tobias T1 - Better integrators for functional renormalization group calculations JF - The European Physical Journal B N2 - We analyze a variety of integration schemes for the momentum space functional renormalization group calculation with the goal of finding an optimized scheme. Using the square lattice t-t' Hubbard model as a testbed we define and benchmark the quality. Most notably we define an error estimate of the solution for the ordinary differential equation circumventing the issues introduced by the divergences at the end of the FRG flow. Using this measure to control for accuracy we find a threefold reduction in number of required integration steps achievable by choice of integrator. We herewith publish a set of recommended choices for the functional renormalization group, shown to decrease the computational cost for FRG calculations and representing a valuable basis for further investigations. KW - functional renormalization group KW - FRG KW - FRG calculations KW - integrators KW - ordinary differential equations KW - ODE Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325131 SN - 1434-6028 VL - 95 IS - 7 ER - TY - JOUR A1 - Spano, Nicola T1 - Husserl’s taxonomy of action JF - Husserl Studies N2 - In the present article I discuss, in confrontation with the most recent studies on Husserl’s phenomenology of acting and willing, the taxonomy of action that is collected in the volume ‘Wille und Handlung’ of the Husserliana edition Studien zur Struktur des Bewussteins. In so doing, I first present Husserl’s universal characterization of action (Handlung) as a volitional process (willentlicher Vorgang). Then, after clarifying what it means for a process to have a character of volitionality (Willentlichkeit), I illustrate the various types of actions, which Husserl distinguishes as ‘straightforward’ (schlicht) or ‘deciding’ (entscheidend), ‘primary’ (primär) or ‘secondary’ (sekundär), ‘inner’ (innere) or ‘outer’ (äußere), ‘immediate’ (unmittelbar) or mediate (mittelbar), ‘simple’ (einfach) or ‘compound’ (zusammengesetzt). Finally, I consider Husserl’s discussion of the direction and foundation of action. KW - Edmund Husserl KW - action KW - phenomenology of acting and willing Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324744 SN - 0167-9848 VL - 38 IS - 3 ER - TY - JOUR A1 - Dedukh, Dmitrij A1 - Da Cruz, Irene A1 - Kneitz, Susanne A1 - Marta, Anatolie A1 - Ormanns, Jenny A1 - Tichopád, Tomáš A1 - Lu, Yuan A1 - Alsheimer, Manfred A1 - Janko, Karel A1 - Schartl, Manfred T1 - Achiasmatic meiosis in the unisexual Amazon molly, Poecilia formosa JF - Chromosome Research N2 - Unisexual reproduction, which generates clonal offspring, is an alternative strategy to sexual breeding and occurs even in vertebrates. A wide range of non-sexual reproductive modes have been described, and one of the least understood questions is how such pathways emerged and how they mechanistically proceed. The Amazon molly, Poecilia formosa, needs sperm from males of related species to trigger the parthenogenetic development of diploid eggs. However, the mechanism, of how the unreduced female gametes are produced, remains unclear. Cytological analyses revealed that the chromosomes of primary oocytes initiate pachytene but do not proceed to bivalent formation and meiotic crossovers. Comparing ovary transcriptomes of P. formosa and its sexual parental species revealed expression levels of meiosis-specific genes deviating from P. mexicana but not from P. latipinna. Furthermore, several meiosis genes show biased expression towards one of the two alleles from the parental genomes. We infer from our data that in the Amazon molly diploid oocytes are generated by apomixis due to a failure in the synapsis of homologous chromosomes. The fact that this failure is not reflected in the differential expression of known meiosis genes suggests the underlying molecular mechanism may be dysregulation on the protein level or misexpression of a so far unknown meiosis gene, and/or hybrid dysgenesis because of compromised interaction of proteins from diverged genomes. KW - meiosis KW - parthenogenesis KW - synaptonemal complex KW - recombination KW - crossing-over KW - achiasmatic KW - transcriptome KW - oogenesis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325128 VL - 30 IS - 4 ER - TY - JOUR A1 - Fricke, Ute A1 - Redlich, Sarah A1 - Zhang, Jie A1 - Tobisch, Cynthia A1 - Rojas-Botero, Sandra A1 - Benjamin, Caryl S. A1 - Englmeier, Jana A1 - Ganuza, Cristina A1 - Riebl, Rebekka A1 - Uhler, Johannes A1 - Uphus, Lars A1 - Ewald, Jörg A1 - Kollmann, Johannes A1 - Steffan-Dewenter, Ingolf T1 - Plant richness, land use and temperature differently shape invertebrate leaf-chewing herbivory on plant functional groups JF - Oecologia N2 - Higher temperatures can increase metabolic rates and carbon demands of invertebrate herbivores, which may shift leaf-chewing herbivory among plant functional groups differing in C:N (carbon:nitrogen) ratios. Biotic factors influencing herbivore species richness may modulate these temperature effects. Yet, systematic studies comparing leaf-chewing herbivory among plant functional groups in different habitats and landscapes along temperature gradients are lacking. This study was conducted on 80 plots covering large gradients of temperature, plant richness and land use in Bavaria, Germany. We investigated proportional leaf area loss by chewing invertebrates (‘herbivory’) in three plant functional groups on open herbaceous vegetation. As potential drivers, we considered local mean temperature (range 8.4–18.8 °C), multi-annual mean temperature (range 6.5–10.0 °C), local plant richness (species and family level, ranges 10–51 species, 5–25 families), adjacent habitat type (forest, grassland, arable field, settlement), proportion of grassland and landscape diversity (0.2–3 km scale). We observed differential responses of leaf-chewing herbivory among plant functional groups in response to plant richness (family level only) and habitat type, but not to grassland proportion, landscape diversity and temperature—except for multi-annual mean temperature influencing herbivory on grassland plots. Three-way interactions of plant functional group, temperature and predictors of plant richness or land use did not substantially impact herbivory. We conclude that abiotic and biotic factors can assert different effects on leaf-chewing herbivory among plant functional groups. At present, effects of plant richness and habitat type outweigh effects of temperature and landscape-scale land use on herbivory among legumes, forbs and grasses. KW - climate KW - ecosystem function KW - land use KW - plant guilds KW - plant–insect interactions Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325079 VL - 199 IS - 2 ER - TY - JOUR A1 - Zupanc, Günther K. H. A1 - Rössler, Wolfgang T1 - Government funding of research beyond biomedicine: challenges and opportunities for neuroethology JF - Journal of Comparative Physiology A N2 - Curiosity-driven research is fundamental for neuroethology and depends crucially on governmental funding. Here, we highlight similarities and differences in funding of curiosity-driven research across countries by comparing two major funding agencies—the National Science Foundation (NSF) in the United States and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). We interviewed representatives from each of the two agencies, focusing on general funding trends, levels of young investigator support, career-life balance, and international collaborations. While our analysis revealed a negative trend in NSF funding of biological research, including curiosity-driven research, German researchers in these areas have benefited from a robust positive trend in DFG funding. The main reason for the decrease in curiosity-driven research in the US is that the NSF has only partially been able to compensate for the funding gap resulting from the National Institutes of Health restricting their support to biomedical research using select model organisms. Notwithstanding some differences in funding programs, particularly those relevant for scientists in the postdoctoral phase, both the NSF and DFG clearly support curiosity-driven research. KW - German Research Foundation KW - Government research funding KW - National Science Foundation KW - Deutsche Forschungsgemeinschaft KW - neuroethology Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325113 VL - 208 IS - 3 ER - TY - JOUR A1 - Bittner, Nataly A1 - Boon, Andy A1 - Delbanco, Evert H. A1 - Walter, Christof A1 - Mally, Angela T1 - Assessment of aromatic amides in printed food contact materials: analysis of potential cleavage to primary aromatic amines during simulated passage through the gastrointestinal tract JF - Archives of Toxicology N2 - Recent analyses conducted by German official food control reported detection of the aromatic amides N-(2,4-dimethylphenyl)acetamide (NDPA), N-acetoacetyl-m-xylidine (NAAX) and 3-hydroxy-2-naphthanilide (Naphthol AS) in cold water extracts from certain food contact materials made from paper or cardboard, including paper straws, paper napkins, and cupcake liners. Because aromatic amides may be cleaved to potentially genotoxic primary amines upon oral intake, these findings raise concern that transfer of NDPA, NAAX and Naphthol AS from food contact materials into food may present a risk to human health. The aim of the present work was to assess the stability of NDPA, NAAX and Naphthol AS and potential cleavage to 2,4-dimethylaniline (2,4-DMA) and aniline during simulated passage through the gastrointestinal tract using static in vitro digestion models. Using the digestion model established by the National Institute for Public Health and the Environment (RIVM, Bilthoven, NL) and a protocol recommended by the European Food Safety Authority, potential hydrolysis of the aromatic amides to the respective aromatic amines was assessed by LC–MS/MS following incubation of the aromatic amides with digestive fluid simulants. Time-dependent hydrolysis of NDPA and NAAX resulting in formation of the primary aromatic amine 2,4-DMA was consistently observed in both models. The highest rate of cleavage of NDPA and NAAX was recorded following 4 h incubation with 0.07 M HCl as gastric-juice simulant, and amounted to 0.21% and 0.053%, respectively. Incubation of Naphthol AS with digestive fluid simulants did not give rise to an increase in the concentration of aniline above the background that resulted from the presence of aniline as an impurity of the test compound. Considering the lack of evidence for aniline formation from Naphthol AS and the extremely low rate of hydrolysis of the amide bonds of NDPA and NAAX during simulated passage through the gastrointestinal tract that gives rise to only very minor amounts of the potentially mutagenic and/or carcinogenic aromatic amine 2,4-DMA, risk assessment based on assumption of 100% cleavage to the primary aromatic amines would appear to overestimate health risks related to the presence of aromatic amides in food contact materials. KW - aromatic amides KW - primary aromatic amine KW - food contact materials KW - simulated digestion Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324697 VL - 96 IS - 5 ER - TY - JOUR A1 - Zamò, Alberto A1 - Gerhard-Hartmann, Elena A1 - Ott, German A1 - Anagnostopoulos, Ioannis A1 - Scott, David W. A1 - Rosenwald, Andreas A1 - Rauert-Wunderlich, Hilka T1 - Routine application of the Lymph2Cx assay for the subclassification of aggressive B-cell lymphoma: report of a prospective real-world series JF - Virchows Archiv N2 - The subclassification of diffuse large B-cell lymphoma (DLBCL) into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes has become mandatory in the 2017 update of the WHO classification of lymphoid neoplasms and will continue to be used in the WHO 5\(^{th}\) edition. The RNA-based Lymph2Cx assay has been validated as a reliable surrogate of high-throughput gene expression profiling assays for distinguishing between GCB and ABC DLBCL and provides reliable results from formalin-fixed, paraffin-embedded (FFPE) material. This test has been previously used in clinical trials, but experience from real-world routine application is rare. We routinely applied the Lymph2Cx assay to day-to-day diagnostics on a series of 147 aggressive B-cell lymphoma cases and correlated our results with the immunohistochemical subclassification using the Hans algorithm and fluorescence in situ hybridization findings using break-apart probes for MYC, BCL2, and BCL6. The routine use of the Lymph2Cx assay had a high technical success rate (94.6%) with a low rate of failure due to poor material and/or RNA quality. The Lymph2Cx assay was discordant with the Hans algorithm in 18% (23 of 128 cases). Discordant cases were mainly classified as GCB by the Hans algorithm and as ABC by Lymph2Cx (n = 11, 8.6%). Only 5 cases (3.9%) were classified as non-GCB by the Hans algorithm and as GCB by Lymph2Cx. Additionally, 5.5% of cases (n = 7) were left unclassified by Lymph2Cx, whereas they were defined as GCB (n = 4) or non-GCB (n = 3) by the Hans algorithm. Our data support the routine applicability of the Lymph2Cx assay. KW - diffuse large B-cell lymphoma KW - Hans algorithm KW - Lymph2Cx assay KW - cell of origin Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324686 VL - 481 IS - 6 ER - TY - JOUR A1 - Scorcelletti, Matteo A1 - Kara, Serhan A1 - Zange, Jochen A1 - Jordan, Jens A1 - Semler, Oliver A1 - Schönau, Eckhard A1 - Rittweger, Jörn A1 - Ireland, Alex A1 - Seefried, Lothar T1 - Lower limb bone geometry in adult individuals with X-linked hypophosphatemia: an observational study JF - Osteoporosis International N2 - Summary We assessed lower-limb geometry in adults with X-linked hypophosphatemia (XLH) and controls. We found large differences in multiple measures including femoral and tibial torsion, bowing and cross-sectional area and acetabular version and coverage which may contribute to clinical problems such as osteoarthritis, fractures and altered gait common in XLH. Purpose Individuals with X-linked hypophosphatemia (XLH) are at risk of lower-limb deformities and early onset of osteoarthritis. These two factors may be linked, as altered biomechanics is a risk factor for osteoarthritis. This exploratory evaluation aims at providing clues and concepts for this association to facilitate future larger-scale and longitudinal studies on that aspect. Methods For this observational study, 13 patients with XLH, aged 18–65 years (6 female), were compared with sex-, age- and weight-matched healthy individuals at a single German research centre. Femoral and hip joint geometry, including femoral and tibial torsion and femoral and tibial shaft bowing, bone cross-sectional area (CSA) and acetabular version and coverage were measured from magnetic resonance imaging (MRI) scans. Results Total femoral torsion was 29° lower in individuals with XLH than in controls (p < 0.001), mainly resulting from lower intertrochanteric torsion (ITT) (p < 0.001). Femoral lateral and frontal bowing, tibial frontal bowing, mechanical axis, femoral mechanical–anatomical angle, acetabular version and acetabular coverage were all greater and tibial torsion lower in individuals with XLH as compared to controls (all p < 0.05). Greater femoral total and marrow cavity CSA, greater tibial marrow cavity CSA and lower cortical CSA were observed in XLH (all p < 0.05). Discussion We observed large differences in clinically relevant measures of tibia and particularly femur bone geometry in individuals with XLH compared to controls. These differences may plausibly contribute to clinical manifestations of XLH such as early-onset osteoarthritis, pseudofractures and altered gait and therefore should be considered when planning corrective surgeries. KW - bone KW - femur KW - geometry KW - shape KW - XLH Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324655 VL - 33 IS - 7 ER - TY - JOUR A1 - Higuchi, Takahiro A1 - Serfling, Sebastian E. A1 - Rowe, Steven P. A1 - Werner, Rudolf A. T1 - Therapeutic effects of lipid lowering medications on myocardial blood flow, inflammation, and sympathetic nerve activity using nuclear techniques JF - Current Cardiology Reports N2 - Purpose of Review Statins are routinely applied in patients with coronary artery disease, as they allow significantly to reduce blood cholesterol levels. Although those drugs are endorsed by current guidelines and prescribed routinely, a substantial portion of patients are still statin-intolerant and image-piloted strategies may then be helpful to identify patients that need further intensified treatment, e.g., to initiate treatment with proprotein convertase subtilisin / kexin type 9 inhibitors (PCSK9i). In addition, it has also been advocated that statins exhibit nonlipid, cardio-protective effects including improved cardiac nerve integrity, blood flow, and anti-inflammatory effects in congestive heart failure (HF) patients. Recent Findings In subjects after myocardial infarction treated with statins, \(^{123}\)I-metaiodobenzylguanidine (MIBG) scintigraphy has already revealed enhanced cardiac nerve function relative to patients without statins. In addition, all of those aforementioned statin-targeted pathways in HF can be visualized and monitored using dedicated cardiac radiotracers, e.g., \(^{123}\)I-MIBG or \(^{18}\)F-AF78 (for cardiac nerve function), \(^{18}\)F-flurpiridaz (to determine coronary flow) or \(^{68}\)Ga-PentixaFor (to detect inflammation). Summary Statins exhibit various cardio-beneficial effects, including improvement of cardiac nerve function, blood flow, and reduction of inflammation, which can all be imaged using dedicated nuclear cardiac radiotracers. This may allow for in vivo monitoring of statin-induced cardioprotection beyond lipid profiling in HF patients. KW - sympathetic nervous system KW - cardiac nerve KW - MIBG KW - inflammation KW - blood flow KW - statin Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324599 VL - 24 IS - 12 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Bundschuh, Ralph A. A1 - Weinzierl, Franz-Xaver A1 - Serfling, Sebastian E. A1 - Kosmala, Aleksander A1 - Seitz, Anna Katharina A1 - Kübler, Hubert A1 - Buck, Andreas K. A1 - Essler, Markus A1 - Werner, Rudolf A. T1 - mCRPC patients with PSA fluctuations under radioligand therapy have comparable survival benefits relative to patients with sustained PSA decrease JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - Introduction In men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy. Materials and methods In this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan–Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle). Results Sixty-one out of one hundred seventy-six (34.7%) patients showed a sustained increase and 86/176 (48.8%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95% CI 0.22–0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95% CI 0.30–0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95% CI 0.78–2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95% CI 0.38–4.05; P = 0.68). Conclusion Initial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression. KW - radioligand therapy KW - late response KW - flare phenomenon KW - PSA KW - prostate cancer KW - PSMA Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324562 VL - 49 IS - 13 ER -