TY - JOUR A1 - Matler, Alexander A1 - Arrowsmith, Merle A1 - Schorr, Fabian A1 - Hermann, Alexander A1 - Hofmann, Alexander A1 - Lenczyk, Carsten A1 - Braunschweig, Holger T1 - Reactivity of Terminal Iron Borylenes and Bis(borylenes) with Carbodiimides: Cycloaddition, Metathesis, Insertion and C−H Activation Pathways JF - European Journal of Inorganic Chemistry N2 - The reactions of carbodiimides with the iron arylborylene complex [Fe=BDur(CO)\(_{3}\)(PMe\(_{3}\))] (Dur=2,3,5,6-Me\(_{4}\)C\(_{6}\)H) and the iron bis(borylene) complex [Fe{=BDur}{=BN(SiMe\(_{3}\))\(_{2}\)}(CO)\(_{3}\)] yield a wide variety of temperature-dependent products, including known FeBNC and novel FeBNB metallacycles, complexes of N-heterocyclic boracarbene and spiro-boracarbene ligands and a unique 1,3,2,4-diazadiborolyl pianostool complex, characterized by NMR spectroscopy and X-ray crystallography. The product distributions can be rationalized by considering sequences of cycloaddition, metathesis, insertion, and C−H activation pathways mainly governed by sterics. KW - structure elucidation KW - borylene complexes KW - cycloaddition KW - metathesis KW - reaction mechanisms Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257397 VL - 2021 IS - 45 ER - TY - JOUR A1 - Stangl, Stephanie A1 - Haas, Kirsten A1 - Eichner, Felizitas A. A1 - Grau, Anna A1 - Selig, Udo A1 - Ludwig, Timo A1 - Fehm, Tanja A1 - Stübner, Tanja A1 - Rashid, Asarnusch A1 - Kerscher, Alexander A1 - Bargou, Ralf A1 - Hermann, Silke A1 - Arndt, Volker A1 - Meyer, Martin A1 - Wildner, Manfred A1 - Faller, Hermann A1 - Schrauder, Michael G. A1 - Weigel, Michael A1 - Schlembach, Ulrich A1 - Heuschmann, Peter U. A1 - Wöckel, Achim T1 - Development and proof-of-concept of a multicenter, patient-centered cancer registry for breast cancer patients with metastatic disease — the “Breast cancer care for patients with metastatic disease” (BRE-4-MED) registry JF - Pilot and Feasibility Studies N2 - Background: Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus oncontrolling for disease symptoms and maintaining high quality of life. Information on individual needs of patients andtheir relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or arenot routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adaptedfor these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data. Methods: The concept for patient-centered “Breast cancer care for patients with metastatic disease”(BRE-4-MED)registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germanycomprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information includingroutine data from established Cancer Registries in different federal states, treating physicians in hospital as well as inoutpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancerregistry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-basedquestionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitorneeds, progression, and therapy change of individual patients. Patient’s acceptance and feasibility of data collection inclinical routine was assessed within a proof-of-concept study. Results: The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018.In total n= 31 patients were included in the pilot study, n= 22 patients were followed up after 1 month. Recordlinkage with the Cancer Registries of Bavaria and Baden-Württemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n= 7 participants. The feasibility of the registry concept in clinical routine waspositively evaluated by the participating hospitals. Conclusion: The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needsof family members, and raising clinical parameters from primary and secondary data sources as well as m-healthapplications are feasible and accepted in an incurable cancer collective. KW - Metastatic breast cancer KW - Patient-centered registry KW - Patient’s needs KW - m-Health KW - Health care service research Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229149 VL - 6 ER - TY - JOUR A1 - Lüke, Florian A1 - Haller, Florian A1 - Utpatel, Kirsten A1 - Krebs, Markus A1 - Meidenbauer, Norbert A1 - Scheiter, Alexander A1 - Spoerl, Silvia A1 - Heudobler, Daniel A1 - Sparrer, Daniela A1 - Kaiser, Ulrich A1 - Keil, Felix A1 - Schubart, Christoph A1 - Tögel, Lars A1 - Einhell, Sabine A1 - Dietmaier, Wolfgang A1 - Huss, Ralf A1 - Dintner, Sebastian A1 - Sommer, Sebastian A1 - Jordan, Frank A1 - Goebeler, Maria-Elisabeth A1 - Metz, Michaela A1 - Haake, Diana A1 - Scheytt, Mithun A1 - Gerhard-Hartmann, Elena A1 - Maurus, Katja A1 - Brändlein, Stephanie A1 - Rosenwald, Andreas A1 - Hartmann, Arndt A1 - Märkl, Bruno A1 - Einsele, Hermann A1 - Mackensen, Andreas A1 - Herr, Wolfgang A1 - Kunzmann, Volker A1 - Bargou, Ralf A1 - Beckmann, Matthias W. A1 - Pukrop, Tobias A1 - Trepel, Martin A1 - Evert, Matthias A1 - Claus, Rainer A1 - Kerscher, Alexander T1 - Identification of disparities in personalized cancer care — a joint approach of the German WERA consortium JF - Cancers N2 - (1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in Würzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy. KW - precision oncology KW - MTB KW - patient access KW - cancer care KW - outreach KW - real world data KW - outcomes research Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290311 SN - 2072-6694 VL - 14 IS - 20 ER - TY - JOUR A1 - Sudarevic, Boban A1 - Troya, Joel A1 - Fuchs, Karl-Hermann A1 - Hann, Alexander A1 - Vereczkei, Andras A1 - Meining, Alexander T1 - Design and development of a flexible 3D-printed endoscopic grasping instrument JF - Applied Sciences N2 - (1) Background: Interventional endoscopic procedures are growing more popular, requiring innovative instruments and novel techniques. Three-dimensional printing has demonstrated great potential for the rapid development of prototypes that can be used for the early assessment of various concepts. In this work, we present the development of a flexible endoscopic instrument and explore its potential benefits. (2) Methods: The properties of the instrument, such as its maneuverability, flexibility, and bending force, were evaluated in a series of bench tests. Additionally, the effectiveness of the instrument was evaluated in an ex vivo porcine model by medical experts, who graded its properties and performance. Furthermore, the time necessary to complete various interventional endoscopic tasks was recorded. (3) Results: The instrument achieved bending angles of ±216° while achieving a bending force of 7.85 (±0.53) Newtons. The time needed to reach the operating region was 120 s median, while it took 70 s median to insert an object in a cavity. Furthermore, it took 220 s median to insert the instrument and remove an object from the cavity. (4) Conclusions: This study presents the development of a flexible endoscopic instrument using three-dimensional printing technology and its evaluation. The instrument demonstrated high bending angles and forces, and superior properties compared to the current state of the art. Furthermore, it was able to complete various interventional endoscopic tasks in minimal time, thus potentially leading to the improved safety and effectiveness of interventional endoscopic procedures in the future. KW - endoscopy KW - endoscopic intervention KW - 3D printing KW - endoscopic instruments KW - minimally invasive surgery KW - rapid prototyping Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319186 SN - 2076-3417 VL - 13 IS - 9 ER - TY - JOUR A1 - Strinitz, Marc A1 - Pham, Mirko A1 - März, Alexander G. A1 - Feick, Jörn A1 - Weidner, Franziska A1 - Vogt, Marius L. A1 - Essig, Fabian A1 - Neugebauer, Hermann A1 - Stoll, Guido A1 - Schuhmann, Michael K. A1 - Kollikowski, Alexander M. T1 - Immune cells invade the collateral circulation during human stroke: prospective replication and extension JF - International Journal of Molecular Sciences N2 - It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R\(^2\) = 0.09696, p = 0.0373) and (4) greater infarct extent (R\(^2\) = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment. KW - ischemic stroke KW - cerebral ischemia KW - mechanical thrombectomy KW - large vessel occlusion KW - leukocytes KW - neutrophils KW - collateral circulation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284281 SN - 1422-0067 VL - 22 IS - 17 ER - TY - JOUR A1 - Schmidt, Uwe A1 - Werner, Luis A1 - Arrowsmith, Merle A1 - Deissenberger, Andrea A1 - Hermann, Alexander A1 - Hofmann, Alexander A1 - Ullrich, Stefan A1 - Mattock, James D. A1 - Vargas, Alfredo A1 - Braunschweig, Holger T1 - Trans‐selektive Dihydroborierung eines cis‐Diborens durch Insertion: Synthese eines linearen sp\(^3\)‐sp\(^2\)‐sp\(^3\)‐Triborans und anschließende Kationisierung JF - Angewandte Chemie N2 - Die Reaktion zwischen Aryl‐ und Amino(dihydro)boranen und Dibora[2]ferrocenophan 1 führt zur Bildung von 1,3‐trans‐Dihydrotriboranen durch formale Hydrierung und Insertion eines Borylens in die B=B Doppelbindung. Die Aryltriboran‐Derivate unterliegen einer reversiblen Photoisomerisierung zugunsten eines cis‐1,2‐μ‐H‐3‐Hydrotriborans, während eine Hydridabstraktion zu kationischen Triboranen führt, welche die ersten doppelt basenstabilisierten B\(_3\)H\(_4\)\(^+\)‐Analoga darstellen. KW - Diboren KW - Hydroborierung KW - Kation KW - Photoisomerisierung KW - Triboran Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219713 VL - 132 IS - 1 ER - TY - JOUR A1 - Schmidt, Uwe A1 - Werner, Luis A1 - Arrowsmith, Merle A1 - Deissenberger, Andrea A1 - Hermann, Alexander A1 - Hofmann, Alexander A1 - Ullrich, Stefan A1 - Mattock, James D. A1 - Vargas, Alfredo A1 - Braunschweig, Holger T1 - trans-Selective Insertional Dihydroboration of a cis-Diborene: Synthesis of Linear sp\(^3\)-sp\(^2\)-sp\(^3\)-Triboranes and Subsequent Cationization JF - Angewandte Chemie International Edition N2 - The reaction of aryl‐ and amino(dihydro)boranes with dibora[2]ferrocenophane 1 leads to the formation 1,3‐trans ‐dihydrotriboranes by formal hydrogenation and insertion of a borylene unit into the B=B bond. The aryltriborane derivatives undergo reversible photoisomerization to the cis ‐1,2‐μ‐H‐3‐hydrotriboranes, while hydride abstraction affords cationic triboranes, which represent the first doubly base‐stabilized B3H4\(^+\) analogues. KW - cations KW - hydroboration KW - photoisomerization KW - triboranes KW - diborenes Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208090 VL - 59 IS - 1 ER - TY - JOUR A1 - Böhnke, Julian A1 - Brückner, Tobias A1 - Hermann, Alexander A1 - González-Belman, Oscar F. A1 - Arrowsmith, Merle A1 - Jiménez-Halla, J. Oscar C. A1 - Braunschweig, Holger T1 - Single and double activation of acetone by isolobal B≡N and B≡B triple bonds JF - Chemical Science N2 - B≡N and B≡B triple bonds induce C-H activation of acetone to yield a (2-propenyloxy)aminoborane and an unsymmetrical 1-(2- propenyloxy)-2-hydrodiborene, respectively. DFT calculations showed that, despite their stark electronic differences, both the B≡N and B≡B triple bonds activate acetone via a similar coordination-deprotonation mechansim. In contrast, the reaction of acetone with a cAAC-supported diboracumulene yielded a unique 1,2,3-oxadiborole, which according to DFT calculations also proceeds via an unsymmetrical diborene, followed by intramolecular hydride migration and a second C-H activation of the enolate ligand. KW - acetone KW - diborynes KW - iminoboranes KW - boron KW - small-molecule activation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164286 VL - 9 ER - TY - INPR A1 - Cid, Jessica A1 - Hermann, Alexander A1 - Radcliffe, James E. A1 - Curless, Liam D. A1 - Braunschweig, Holger A1 - Ingleson, Michael J. T1 - Synthesis of Unsymmetrical Diboron(5) Compounds and Their Conversion to Diboron(5) Cations T2 - Organometallics N2 - Reaction of bis-catecholatodiboron-NHC adducts, B\(_2\)Cat\(_2\)(NHC), (NHC = IMe (tetramethylimidazol-2-ylidene), IMes (1,3-dimesitylimidazol-2-ylidene) or IDIPP (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)) with BCl3 results in the replacement of the catecholato group bound to the four coordinate boron with two chlorides to yield diboron(5) Lewis acid-base adducts of formula CatB-BCl\(_2\)(NHC). These compounds are precursors to diboron(5) monocations, accessed by adding AlCl\(_3\) or K[B(C\(_6\)F\(_5\))\(_4\)] as halide abstraction agents in the presence of a Lewis base. The substitution of the chlorides of CatB-BCl\(_2\)(NHC) for hydrides is achieved using Bu\(_3\)SnH and a halide abstracting agent to form 1,1-dihydrodiboron(5) compounds, CatB-BH\(_2\)(NHC). Attempts to generate diboron(4) monocations of formula [CatB-B(Y)(NHC)]\(^+\) (Y = Cl or H) led to the rapid formation of CatBY. KW - diboron KW - boronium cations KW - boron KW - Lewis acids KW - electrophiles Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164299 N1 - This document is the unedited Author's version of a Submitted Work that was subsequently accepted for publication in Organometallics, copyright © 2018 American Chemical Society after peer review. To access the final edited and published work see dx.doi.org/10.1021/acs.organomet.8b00288 ER - TY - INPR A1 - Hermann, Alexander A1 - Cid, Jessica A1 - Mattock, James D. A1 - Dewhurst, Rian D. A1 - Krummenacher, Ivo A1 - Vargas, Alfredo A1 - Ingleson, Michael J. A1 - Braunschweig, Holger T1 - Diboryldiborenes: π‐Conjugated B\(_4\) Chains Isoelectronic to the Butadiene Dication T2 - Angewandte Chemie, International Edition N2 - sp\(^2\)–sp\(^3\) diborane species based on bis(catecholato)diboron and N-heterocyclic carbenes (NHCs) are subjected to catechol/bromide exchange selectively at the sp\(^3\) boron atom. The reduction of the resulting 1,1-dibromodiborane adducts led to reductive coupling and isolation of doubly NHC-stabilized 1,2-diboryldiborenes. These compounds are the first examples of molecules exhibiting pelectron delocalization over an all-boron chain. KW - diboranes KW - diborenes KW - N-heterocyclic carbenes KW - boron chains KW - pi-conjugation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167977 N1 - This is the pre-peer reviewed version of the following article: A. Hermann, J. Cid, J. D. Mattock, R. D. Dewhurst, I. Krummenacher, A. Vargas, M. J. Ingleson, H. Braunschweig, Angew. Chem. Int. Ed. 2018, 57, 10091, which has been published in final form at https://doi.org/10.1002/anie.201805394. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. ER - TY - INPR A1 - Hermann, Alexander A1 - Arrowsmith, Merle A1 - Trujillo-Gonzalez, Daniel A1 - Jiménez-Halla, J. Oscar C. A1 - Vargas, Alfredo A1 - Braunschweig, Holger T1 - Trapping of a Borirane Intermediate in the Reductive Coupling of an Arylborane to a Diborene T2 - Journal of the American Chemical Society N2 - The reductive coupling of an NHC-stabilized aryldibromoborane yields a mixture of trans- and cis-diborenes in which the aryl groups are coplanar with the diborene core. Under dilute reduction conditions two diastereomers of a borirane-borane intermediate are isolated, which upon further reduction give rise to the aforementioned diborene mixture. DFT calculations suggest a mechanism proceeding via nucleophilic attack of a dicoordinate borylene intermediate on the aryl ring and subsequent intramolecular B-B bond formation. KW - boron KW - reactive intermediates KW - reductive coupling Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203140 N1 - This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Journal of the American Chemical Society, copyright © American Chemical Society after peer review. To access the final edited and published work see https://doi.org/10.1021/jacs.0c02306 ER - TY - THES A1 - Hermann, Alexander T1 - Untersuchung von B-B-Doppelbindungen als Bestandteil konjugierter p-Systeme T1 - Integration of B-B Double Bonds in conjugated p-Systems N2 - Der erste Teil dieser Arbeit beschäftigt sich mit der "Synthese und Reaktivität sterisch anspruchsvoller Iminoborane". Dabei war es möglich, ausgehend von einem Terphenylamin geeignete Aminoborane zu synthetisieren, welche anschließend mit starken, nicht-nukleophilen Basen umgesetzt wurden. Mittels formaler HCl-Eliminierung mit LiTmp gelang auf diese Weise die Darstellung sterisch anspruchsvoller Iminoborane. Der zweite Teil dieser Arbeit befasst sich mit der "Untersuchung von B-B-Doppelbindungen als Bestandteil konjugierter p-Systeme". Durch die Verwendung von sterisch wenig anspruchsvollen Liganden oder Boryl-Substituenten war es möglich planare Diboren-Systeme zu generieren und darüberhinaus Divinyldiborene darzustellen. N2 - The first part of this work deals with the "Synthesis and Reactivity of Sterically Demanding Iminoboranes". Starting with a terphenylamine, it was possible to synthesize aminoboranes, which were then reacted with strong, non-nucleophilic bases. Formal HCl elimination mit LiTmp thus enabled the preparation of sterically demanding iminoboranes. The second part of this thesis focuses on the "Integration of B-B Double Bonds in conjugated p-Systems". By using sterically low damanding ligands or boryl-substituents it was possible to generate planar diborene structures and to synthesize divinyldiborenes. KW - Konjugation KW - Hauptgruppenelementverbindungen KW - Diborene KW - Hauptgruppenelementchemie KW - Conjugation KW - Diborene KW - Main Group Chemistry Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204592 ER - TY - JOUR A1 - Jaschke, Alexander A1 - Chung, Bomee A1 - Hesse, Deike A1 - Kluge, Reinhart A1 - Zahn, Claudia A1 - Moser, Markus A1 - Petzke, Klaus-Jürgen A1 - Brigelius-Flohé, Regina A1 - Puchkov, Dmytro A1 - Koepsell, Hermann A1 - Heeren, Joerg A1 - Joost, Hans-Georg A1 - Schürmann, Annette T1 - The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium JF - Human Molecular Genetics N2 - The uptake and processing of dietary lipids by the small intestine is a multistep process that involves several steps including vesicular and protein transport. The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) controls the ARF-like 1 (ARL1)-mediated Golgi recruitment of GRIP domain proteins which in turn bind several Rab-GTPases. Here, we describe the essential role of ARFRP1 and its interaction with Rab2 in the assembly and lipidation of chylomicrons in the intestinal epithelium. Mice lacking Arfrp1 specifically in the intestine \((Arfrp1^{vil−/−})\) exhibit an early post-natal growth retardation with reduced plasma triacylglycerol and free fatty acid concentrations. \(Arfrp1^{vil−/−}\) enterocytes as well as Arfrp1 mRNA depleted Caco-2 cells absorbed fatty acids normally but secreted chylomicrons with a markedly reduced triacylglycerol content. In addition, the release of apolipoprotein A-I (ApoA-I) was dramatically decreased, and ApoA-I accumulated in the \(Arfrp1^{vil−/−}\) epithelium, where it predominantly co-localized with Rab2. The release of chylomicrons from Caco-2 was markedly reduced after the suppression of Rab2, ARL1 and Golgin-245. Thus, the GTPase ARFRP1 and its downstream proteins are required for the lipidation of chylo­microns and the assembly of ApoA-I to these particles in the Golgi of intestinal epithelial cells. KW - ARF Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125658 VL - 21 IS - 14 ER - TY - INPR A1 - Schmidt, Uwe A1 - Fantuzzi, Felipe A1 - Arrowsmith, Merle A1 - Hermann, Alexander A1 - Prieschl, Dominic A1 - Rempel, Anna A1 - Engels, Bernd A1 - Braunschweig, Holger T1 - Tuneable reduction of cymantrenylboranes to diborenes or borylene-derived boratafulvenes T2 - Chemical Communications N2 - Whereas the reduction of N-heterocyclic carbene (NHC)-stabilised cymantrenyldibromoboranes, (NHC)BBr\(_2\)Cym, in benzene results in formation of the corresponding diborenes (NHC)\(_2\)B\(_2\)Cym\(_2\), a change of solvent to THF yields a borylene of the form (NHC)\(_2\)BCym, stabilised through its boratafulvene resonance form. KW - Borylene KW - Diborene KW - Boranes Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222149 ER - TY - JOUR A1 - Zhou, Xiang A1 - Dierks, Alexander A1 - Kertels, Olivia A1 - Kircher, Malte A1 - Schirbel, Andreas A1 - Samnick, Samuel A1 - Buck, Andreas K. A1 - Knorz, Sebastian A1 - Böckle, David A1 - Scheller, Lukas A1 - Messerschmidt, Janin A1 - Barakat, Mohammad A1 - Kortüm, K. Martin A1 - Rasche, Leo A1 - Einsele, Hermann A1 - Lapa, Constantin T1 - 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in patients with smoldering multiple myeloma: imaging pattern and clinical features JF - Cancers N2 - This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV\(_{mean}\)) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV\(_{mean}\) of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR\(_{mean}\)) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR\(_{mean}\) in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR\(_{max}\) of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM. KW - 18F-FDG PET/CT KW - 11C-Methionine PET/CT KW - 68Ga-Pentixafor PET/CT KW - smoldering myeloma Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211240 SN - 2072-6694 VL - 12 IS - 8 ER - TY - JOUR A1 - Haarmann, Axel A1 - Vollmuth, Christoph A1 - Kollikowski, Alexander M. A1 - Heuschmann, Peter U. A1 - Pham, Mirko A1 - Stoll, Guido A1 - Neugebauer, Hermann A1 - Schuhmann, Michael K. T1 - Vasoactive soluble endoglin: a novel biomarker indicative of reperfusion after cerebral large-vessel occlusion JF - Cells N2 - Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion. KW - endoglin KW - brain endothelium KW - stroke KW - shedding KW - mechanical thrombectomy KW - hypoxia KW - reperfusion injury KW - biomarker Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304995 SN - 2073-4409 VL - 12 IS - 2 ER - TY - JOUR A1 - Steinhardt, Maximilian Johannes A1 - Zhou, Xiang A1 - Krummenast, Franziska A1 - Meckel, Katharina A1 - Nickel, Katharina A1 - Böckle, David A1 - Messerschmidt, Janin A1 - Knorz, Sebastian A1 - Dierks, Alexander A1 - Heidemeier, Anke A1 - Lapa, Constantin A1 - Einsele, Hermann A1 - Rasche, Leo A1 - Kortüm, Klaus Martin T1 - Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma JF - International Journal of Immunopathology and Pharmacology N2 - We report on a currently 76-year-old female patient with relapsed/refractory (RR) multiple myeloma (MM) treated at our institution. This patient had received six lines of therapy including tandem autologous stem cell transplant, proteasome inhibitor, immunomodulatory drugs and CD38 antibody MOR202. At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab (“Pom-PAD-Dara”), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM. KW - CD38 KW - MOR202 KW - daratumumab KW - multiple myeloma KW - refractory KW - relapse Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236235 VL - 34 ER - TY - JOUR A1 - Grunz, Jan-Peter A1 - Kunz, Andreas Steven A1 - Baumann, Freerk T. A1 - Hasenclever, Dirk A1 - Sieren, Malte Maria A1 - Heldmann, Stefan A1 - Bley, Thorsten Alexander A1 - Einsele, Hermann A1 - Knop, Stefan A1 - Jundt, Franziska T1 - Assessing osteolytic lesion size on sequential CT scans is a reliable study endpoint for bone remineralization in newly diagnosed multiple myeloma JF - Cancers N2 - Multiple myeloma (MM) frequently induces persisting osteolytic manifestations despite hematologic treatment response. This study aimed to establish a biometrically valid study endpoint for bone remineralization through quantitative and qualitative analyses in sequential CT scans. Twenty patients (seven women, 58 ± 8 years) with newly diagnosed MM received standardized induction therapy comprising the anti-SLAMF7 antibody elotuzumab, carfilzomib, lenalidomide, and dexamethasone (E-KRd). All patients underwent whole-body low-dose CT scans before and after six cycles of E-KRd. Two radiologists independently recorded osteolytic lesion sizes, as well as the presence of cortical destruction, pathologic fractures, rim and trabecular sclerosis. Bland–Altman analyses and Krippendorff’s α were employed to assess inter-reader reliability, which was high for lesion size measurement (standard error 1.2 mm) and all qualitative criteria assessed (α ≥ 0.74). After six cycles of E-KRd induction, osteolytic lesion size decreased by 22% (p < 0.001). While lesion size response did not correlate with the initial lesion size at baseline imaging (Pearson’s r = 0.144), logistic regression analysis revealed that the majority of responding osteolyses exhibited trabecular sclerosis (p < 0.001). The sum of osteolytic lesion sizes on sequential CT scans defines a reliable study endpoint to characterize bone remineralization. Patient level response is strongly associated with the presence of trabecular sclerosis. KW - multiple myeloma KW - bone remineralization KW - computed tomography KW - whole-body imaging Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-362526 SN - 2072-6694 VL - 15 IS - 15 ER - TY - JOUR A1 - Jendretzki, Julia A1 - Henniger, Dorothea A1 - Schiffmann, Lisa A1 - Wolz, Constanze A1 - Kollikowski, Anne A1 - Meining, Alexander A1 - Einsele, Hermann A1 - Winkler, Marcela A1 - Löffler, Claudia T1 - Every fifth patient suffered a high nutritional risk — Results of a prospective patient survey in an oncological outpatient center JF - Frontiers in Nutrition N2 - Introduction Malnutrition in cancer patients often remains undetected and underestimated in clinical practice despite studies revealing prevalences from 20 to 70%. Therefore, this study aimed to identify patient groups exposed to an increased nutritional risk in a university oncological outpatient center. Methods Between May 2017 and January 2018 we screened oncological patients there using the malnutrition universal screening tool (MUST). Qualitative data were collected by a questionnaire to learn about patients’ individual information needs and changes in patients’ diets and stressful personal nutrition restrictions. Results We included 311 patients with various cancers. 20.3% (n = 63) were found to be at high risk of malnutrition, 16.4% (n = 51) at moderate risk despite a mean body mass index (BMI) of 26.5 ± 4.7 kg/m2. The average age was 62.7 (± 11.8) with equal gender distribution (52% women, n = 162). In 94.8% (n = 295) unintended weight loss led to MUST scoring. Patients with gastrointestinal tumors (25%, n = 78) and patients >65 years (22%, n = 68) were at higher risk. Furthermore, there was a significant association between surgery or chemotherapy within six months before survey and a MUST score ≥2 (OR = 3.6). Taste changes, dysphagia, and appetite loss were also particular risk factors (OR = 2.3–3.2). Young, female and normal-weight patients showed most interest in nutrition in cancer. However, only 38% (n = 118) had a nutritional counseling. Conclusion This study confirms that using the MUST score is a valid screening procedure to identify outpatients at risk of developing malnutrition. Here one in five was at high risk, but only 1% would have been detected by BMI alone. Therefore, an ongoing screening procedure with meaningful parameters should be urgently implemented into the clinical routine of cancer outpatients as recommended in international guidelines. KW - nutritional risk screening KW - malnutrition KW - nutritional counseling KW - oncology outpatients KW - MUST-Score KW - nutritional medical needs Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311284 SN - 2296-861X VL - 9 ER - TY - JOUR A1 - Averdunk, Luisa A1 - Bernhagen, Jürgen A1 - Fehnle, Karl A1 - Surowy, Harald A1 - Lüdecke, Hermann-Josef A1 - Mucha, Sören A1 - Meybohm, Patrick A1 - Wieczorek, Dagmar A1 - Leng, Lin A1 - Marx, Gernot A1 - Leaf, David E. A1 - Zarbock, Alexander A1 - Zacharowski, Kai A1 - Bucala, Richard A1 - Stoppe, Christian T1 - The Macrophage Migration Inhibitory Factor (MIF) promoter polymorphisms (rs3063368, rs755622) predict acute kidney injury and death after cardiac surgery JF - Journal of Clinical Medicine N2 - Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT\(_{5–7}\) (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT\(_7\)) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT\(_7\) were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT\(_7\) predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT\(_7\) was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT\(_7\) allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance. KW - acute kidney injury KW - genetic polymorphisms KW - risk prediction KW - (cardiac) surgery KW - inflammatory cytokines KW - clinical studies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213126 SN - 2077-0383 VL - 9 IS - 9 ER -