@article{DunceMilburnGurusaranetal.2018, author = {Dunce, James M. and Milburn, Amy E. and Gurusaran, Manickam and da Cruz, Irene and Sen, Lee T. and Benavente, Ricardo and Davies, Owen R.}, title = {Structural basis of meiotic telomere attachment to the nuclear envelope by MAJIN-TERB2-TERB1}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-07794-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226416}, year = {2018}, abstract = {Meiotic chromosomes undergo rapid prophase movements, which are thought to facilitate the formation of inter-homologue recombination intermediates that underlie synapsis, crossing over and segregation. The meiotic telomere complex (MAJIN, TERB1, TERB2) tethers telomere ends to the nuclear envelope and transmits cytoskeletal forces via the LINC complex to drive these rapid movements. Here, we report the molecular architecture of the meiotic telomere complex through the crystal structure of MAJIN-TERB2, together with light and X-ray scattering studies of wider complexes. The MAJIN-TERB2 2:2 hetero-tetramer binds strongly to DNA and is tethered through long flexible linkers to the inner nuclear membrane and two TRF1-binding 1:1 TERB2-TERB1 complexes. Our complementary structured illumination microscopy studies and biochemical findings reveal a telomere attachment mechanism in which MAJIN-TERB2-TERB1 recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA and form a mature attachment plate.}, language = {en} } @article{DubailHuberChantepieetal.2018, author = {Dubail, Johanne and Huber, C{\´e}line and Chantepie, Sandrine and Sonntag, Stephan and T{\"u}ys{\"u}z, Beyhan and Mihci, Ercan and Gordon, Christopher T. and Steichen-Gersdorf, Elisabeth and Amiel, Jeanne and Nur, Banu and Stolte-Dijkstra, Irene and van Eerde, Albertien M. and van Gassen, Koen L. and Breugem, Corstiaan C. and Stegmann, Alexander and Lekszas, Caroline and Maroofian, Reza and Karimiani, Ehsan Ghayoor and Bruneel, Arnaud and Seta, Nathalie and Munnich, Arnold and Papy-Garcia, Dulce and De La Dure-Molla, Muriel and Cormier-Daire, Val{\´e}rie}, title = {SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-05191-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226377}, year = {2018}, abstract = {Skeletal dysplasia with multiple dislocations are severe disorders characterized by dislocations of large joints and short stature. The majority of them have been linked to pathogenic variants in genes encoding glycosyltransferases, sulfotransferases or epimerases required for glycosaminoglycan synthesis. Using exome sequencing, we identify homozygous mutations in SLC10A7 in six individuals with skeletal dysplasia with multiple dislocations and amelogenesis imperfecta. SLC10A7 encodes a 10-transmembrane-domain transporter located at the plasma membrane. Functional studies in vitro demonstrate that SLC10A7 mutations reduce SLC10A7 protein expression. We generate a Slc10a7-/- mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype. Furthermore, we identify decreased heparan sulfate levels in Slc10a7-/- mouse cartilage and patient fibroblasts. Finally, we find an abnormal N-glycoprotein electrophoretic profile in patient blood samples. Together, our findings support the involvement of SLC10A7 in glycosaminoglycan synthesis and specifically in skeletal development.}, language = {en} } @article{DostalFennelKochetal.2018, author = {Dost{\´a}l, Jakub and Fennel, Franziska and Koch, Federico and Herbst, Stefanie and W{\"u}rthner, Frank and Brixner, Tobias}, title = {Direct observation of exciton-exciton interactions}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-04884-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226271}, year = {2018}, abstract = {Natural light harvesting as well as optoelectronic and photovoltaic devices depend on efficient transport of energy following photoexcitation. Using common spectroscopic methods, however, it is challenging to discriminate one-exciton dynamics from multi-exciton interactions that arise when more than one excitation is present in the system. Here we introduce a coherent two-dimensional spectroscopic method that provides a signal only in case that the presence of one exciton influences the behavior of another one. Exemplarily, we monitor exciton diffusion by annihilation in a perylene bisimide-based J-aggregate. We determine quantitatively the exciton diffusion constant from exciton-exciton-interaction 2D spectra and reconstruct the annihilation-free dynamics for large pump powers. The latter enables for ultrafast spectroscopy at much higher intensities than conventionally possible and thus improves signal-to-noise ratios for multichromophore systems; the former recovers spatio-temporal dynamics for a broad range of phenomena in which exciton interactions are present.}, language = {en} } @article{DoerkPeterlongoMannermaaetal.2019, author = {D{\"o}rk, Thilo and Peterlongo, Peter and Mannermaa, Arto and Bolla, Manjeet K. and Wang, Qin and Dennis, Joe and Ahearn, Thomas and Andrulis, Irene L. and Anton-Culver, Hoda and Arndt, Volker and Aronson, Kristan J. and Augustinsson, Annelie and Beane Freeman, Laura E. and Beckmann, Matthias W. and Beeghly-Fadiel, Alicia and Behrens, Sabine and Bermisheva, Marina and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Stig E. and Brauch, Hiltrud and Brenner, Hermann and Burwinkel, Barbara and Canzian, Federico and Chan, Tsun L. and Chang-Claude, Jenny and Chanock, Stephen J. and Choi, Ji-Yeob and Christiansen, Hans and Clarke, Christine L. and Couch, Fergus J. and Czene, Kamila and Daly, Mary B. and dos-Santos-Silva, Isabel and Dwek, Miriam and Eccles, Diana M. and Ekici, Arif B. and Eriksson, Mikael and Evans, D. Gareth and Fasching, Peter A. and Figueroa, Jonine and Flyger, Henrik and Fritschi, Lin and Gabrielson, Marike and Gago-Dominguez, Manuela and Gao, Chi and Gapstur, Susan M. and Garc{\´i}a-Closas, Montserrat and Garc{\´i}a-S{\´a}enz, Jos{\´e} A. and Gaudet, Mia M. and Giles, Graham G. and Goldberg, Mark S. and Goldgar, David E. and Guen{\´e}l, Pascal and Haeberle, Lothar and Haimann, Christopher A. and H{\aa}kansson, Niclas and Hall, Per and Hamann, Ute and Hartman, Mikael and Hauke, Jan and Hein, Alexander and Hillemanns, Peter and Hogervorst, Frans B. L. and Hooning, Maartje J. and Hopper, John L. and Howell, Tony and Huo, Dezheng and Ito, Hidemi and Iwasaki, Motoki and Jakubowska, Anna and Janni, Wolfgang and John, Esther M. and Jung, Audrey and Kaaks, Rudolf and Kang, Daehee and Kapoor, Pooja Middha and Khusnutdinova, Elza and Kim, Sung-Won and Kitahara, Cari M. and Koutros, Stella and Kraft, Peter and Kristensen, Vessela N. and Kwong, Ava and Lambrechts, Diether and Le Marchand, Loic and Li, Jingmei and Lindstr{\"o}m, Sara and Linet, Martha and Lo, Wing-Yee and Long, Jirong and Lophatananon, Artitaya and Lubiński, Jan and Manoochehri, Mehdi and Manoukian, Siranoush and Margolin, Sara and Martinez, Elena and Matsuo, Keitaro and Mavroudis, Dimitris and Meindl, Alfons and Menon, Usha and Milne, Roger L. and Mohd Taib, Nur Aishah and Muir, Kenneth and Mulligan, Anna Marie and Neuhausen, Susan L. and Nevanlinna, Heli and Neven, Patrick and Newman, William G. and Offit, Kenneth and Olopade, Olufunmilayo I. and Olshan, Andrew F. and Olson, Janet E. and Olsson, H{\aa}kan and Park, Sue K. and Park-Simon, Tjoung-Won and Peto, Julian and Plaseska-Karanfilska, Dijana and Pohl-Rescigno, Esther and Presneau, Nadege and Rack, Brigitte and Radice, Paolo and Rashid, Muhammad U. and Rennert, Gad and Rennert, Hedy S. and Romero, Atocha and Ruebner, Matthias and Saloustros, Emmanouil and Schmidt, Marjanka K. and Schmutzler, Rita K. and Schneider, Michael O. and Schoemaker, Minouk J. and Scott, Christopher and Shen, Chen-Yang and Shu, Xiao-Ou and Simard, Jaques and Slager, Susan and Smichkoska, Snezhana and Southey, Melissa C. and Spinelli, John J. and Stone, Jennifer and Surowy, Harald and Swerdlow, Anthony J. and Tamimi, Rulla M. and Tapper, William J. and Teo, Soo H. and Terry, Mary Beth and Toland, Amanda E. and Tollenaar, Rob A. E. M. and Torres, Diana and Torres-Mej{\´i}a, Gabriela and Troester, Melissa A. and Truong, Th{\´e}r{\`e}se and Tsugane, Shoichiro and Untch, Michael and Vachon, Celine M. and van den Ouweland, Ans M. W. and van Veen, Elke M. and Vijai, Joseph and Wendt, Camilla and Wolk, Alicja and Yu, Jyh-Cherng and Zheng, Wei and Ziogas, Argyrios and Ziv, Elad and Dunnig, Alison and Pharaoh, Paul D. P. and Schindler, Detlev and Devilee, Peter and Easton, Douglas F.}, title = {Two truncating variants in FANCC and breast cancer risk}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, organization = {ABCTB Investigators, NBCS Collaborators}, doi = {10.1038/s41598-019-48804-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222838}, year = {2019}, abstract = {Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95\%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.}, language = {en} } @article{DindasScherzerRoelfsemaetal.2018, author = {Dindas, Julian and Scherzer, S{\"o}nke and Roelfsema, M. Rob G. and Meyer, Katharina von and M{\"u}ller, Heike M. and Al-Rasheid, K. A. S. and Palme, Klaus and Dietrich, Petra and Becker, Dirk and Bennett, Malcolm J. and Hedrich, Rainer}, title = {AUX1-mediated root hair auxin influx governs SCFTIR1/AFB-type Ca2+ signaling}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-03582-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225368}, year = {2018}, abstract = {Auxin is a key regulator of plant growth and development, but the causal relationship between hormone transport and root responses remains unresolved. Here we describe auxin uptake, together with early steps in signaling, in Arabidopsis root hairs. Using intracellular microelectrodes we show membrane depolarization, in response to IAA in a concentration- and pH-dependent manner. This depolarization is strongly impaired in aux1 mutants, indicating that AUX1 is the major transporter for auxin uptake in root hairs. Local intracellular auxin application triggers Ca2+ signals that propagate as long-distance waves between root cells and modulate their auxin responses. AUX1-mediated IAA transport, as well as IAA- triggered calcium signals, are blocked by treatment with the SCFTIR1/AFB - inhibitor auxinole. Further, they are strongly reduced in the tir1afb2afb3 and the cngc14 mutant. Our study reveals that the AUX1 transporter, the SCFTIR1/AFB receptor and the CNGC14 Ca2+ channel, mediate fast auxin signaling in roots.}, language = {en} } @article{DietrichKrugKrastletal.2019, author = {Dietrich, Thomas and Krug, Ralf and Krastl, Gabriel and Tomson, Philip L.}, title = {Restoring the unrestorable! Developing coronal tooth tissue with a minimally invasive surgical extrusion technique}, series = {British Dental Journal}, volume = {226}, journal = {British Dental Journal}, doi = {10.1038/s41415-019-0268-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225333}, pages = {789-793}, year = {2019}, abstract = {Surgical extrusion is a recognised treatment option for teeth that have insufficient coronal tooth structure remaining due to deep caries, resorption or traumatic injury. However, the technique has not been widely adopted, arguably because extraction of a severely compromised tooth may be difficult to achieve in a gentle and predictable way. In this paper, we present our novel approach to surgical extrusion and subsequent management of teeth using a vertical extraction system (Benex), which has become the method of choice in the authors' practice for many teeth that would otherwise be deemed unrestorable. We describe the clinical procedure in detail and discuss the advantages and disadvantages compared to alternative approaches, including surgical crown lengthening and orthodontic extrusion.}, language = {en} } @article{DiehlSchmidLicataGoldhardtetal.2019, author = {Diehl-Schmid, Janine and Licata, Abigail and Goldhardt, Oliver and F{\"o}rstl, Hans and Yakushew, Igor and Otto, Markus and Anderl-Straub, Sarah and Beer, Ambros and Ludolph, Albert Christian and Landwehrmeyer, Georg Bernhard and Levin, Johannes and Danek, Adrian and Fliessbach, Klaus and Spottke, Annika and Fassbender, Klaus and Lyros, Epameinondas and Prudlo, Johannes and Krause, Bernd Joachim and Volk, Alexander and Edbauer, Dieter and Schroeter, Matthias Leopold and Drzezga, Alexander and Kornhuber, Johannes and Lauer, Martin and Grimmer, Timo}, title = {FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations}, series = {Translational Psychiatry}, volume = {9}, journal = {Translational Psychiatry}, organization = {FTLDc Study Group}, doi = {10.1038/s41398-019-0381-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225308}, year = {2019}, abstract = {C9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, 18F-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD. Thalamic metabolism did not correlate with disease severity, duration of disease, or the presence of psychotic symptoms. Against our expectations we could not demonstrate a cerebellar hypometabolism in carriers or non-carriers. Future imaging and neuropathological studies in large patient cohorts are required to further elucidate the central role of the thalamus in C9FTLD.}, language = {en} } @article{DekkerDiekstraPulitetal.2019, author = {Dekker, Annelot M. and Diekstra, Frank P. and Pulit, Sara L. and Tazelaar, Gijs H. P. and van der Spek, Rick A. and van Rheenen, Wouter and van Eijk, Kristel R. and Calvo, Andrea and Brunetti, Maura and Van Damme, Philip and Robberecht, Wim and Hardiman, Orla and McLaughlin, Russell and Chi{\`o}, Adriano and Sendtner, Michael and Ludolph, Albert C. and Weishaupt, Jochen H. and Pardina, Jesus S. Mora and van den Berg, Leonard H. and Veldink, Jan H.}, title = {Exome array analysis of rare and low frequency variants in amyotrophic lateral sclerosis}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-42091-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223686}, year = {2019}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 1 in ~350 individuals. Genetic association studies have established ALS as a multifactorial disease with heritability estimated at ~61\%, and recent studies show a prominent role for rare variation in its genetic architecture. To identify rare variants associated with disease onset we performed exome array genotyping in 4,244 cases and 3,106 controls from European cohorts. In this largest exome-wide study of rare variants in ALS to date, we performed single-variant association testing, gene-based burden, and exome-wide individual set-unique burden (ISUB) testing to identify single or aggregated rare variation that modifies disease risk. In single-variant testing no variants reached exome-wide significance, likely due to limited statistical power. Gene-based burden testing of rare non-synonymous and loss-of-function variants showed NEK1 as the top associated gene. ISUB analysis did not show an increased exome-wide burden of deleterious variants in patients, possibly suggesting a more region-specific role for rare variation. Complete summary statistics are released publicly. This study did not implicate new risk loci, emphasizing the immediate need for future large-scale collaborations in ALS that will expand available sample sizes, increase genome coverage, and improve our ability to detect rare variants associated to ALS.}, language = {en} } @article{deJongDinizSalomaetal.2018, author = {de Jong, Simone and Diniz, Mateus Jose Abdalla and Saloma, Andiara and Gadelha, Ary and Santoro, Marcos L. and Ota, Vanessa K. and Noto, Cristiano and Curtis, Charles and Newhouse, Stephen J. and Patel, Hamel and Hall, Lynsey S. and O'Reilly, Paul F. and Belangero, Sintia I. and Bressan, Rodrigo A. and Breen, Gerome}, title = {Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder}, series = {Communications Biology}, volume = {1}, journal = {Communications Biology}, organization = {Major Depressive Disorder and Bipolar Disorder Working Groups of the Psychiatric Genomics Consortium}, doi = {10.1038/s42003-018-0155-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223622}, year = {2018}, abstract = {Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30\% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.}, language = {en} } @article{DammertBraegelmannOlsenetal.2019, author = {Dammert, Marcel A. and Br{\"a}gelmann, Johannes and Olsen, Rachelle R. and B{\"o}hm, Stefanie and Monhasery, Niloufar and Whitney, Christopher P. and Chalishazar, Milind D. and Tumbrink, Hannah L. and Guthrie, Matthew R. and Klein, Sebastian and Ireland, Abbie S. and Ryan, Jeremy and Schmitt, Anna and Marx, Annika and Ozretić, Luka and Castiglione, Roberta and Lorenz, Carina and Jachimowicz, Ron D. and Wolf, Elmar and Thomas, Roman K. and Poirier, John T. and B{\"u}ttner, Reinhard and Sen, Triparna and Byers, Lauren A. and Reinhardt, H. Christian and Letai, Anthony and Oliver, Trudy G. and Sos, Martin L.}, title = {MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, doi = {10.1038/s41467-019-11371-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223569}, year = {2019}, abstract = {MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promotes sensitivity to cell cycle control inhibition and dependency on MCL1. Furthermore, MYC activation leads to heightened apoptotic priming, intrinsic genotoxic stress and susceptibility to DNA damage checkpoint inhibitors. Finally, combined AURK and CHK1 inhibition substantially prolongs the survival of mice bearing MYC-driven SCLC beyond that of combination chemotherapy. These analyses uncover MYC-paralog-specific regulation of the apoptotic machinery with implications for genotype-based selection of targeted therapeutics in SCLC patients.}, language = {en} } @article{SteuerCostaVanderAuweraGlocketal.2019, author = {Steuer Costa, Wagner and Van der Auwera, Petrus and Glock, Caspar and Liewald, Jana F. and Bach, Maximilian and Sch{\"u}ler, Christina and Wabnig, Sebastian and Oranth, Alexandra and Masurat, Florentin and Bringmann, Henrik and Schoofs, Liliane and Stelzer, Ernst H. K. and Fischer, Sabine C. and Gottschalk, Alexander}, title = {A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, doi = {10.1038/s41467-019-12098-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223273}, year = {2019}, abstract = {Animals must slow or halt locomotion to integrate sensory inputs or to change direction. In Caenorhabditis elegans, the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show RIS functions additionally as a locomotion stop neuron. RIS optogenetic stimulation caused acute and persistent inhibition of locomotion and pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides and GABA. RIS photoactivation allows the animal to maintain its body posture by sustaining muscle tone, yet inactivating motor neuron oscillatory activity. During locomotion, RIS axonal Ca2+ signals revealed functional compartmentalization: Activity in the nerve ring process correlated with locomotion stop, while activity in a branch correlated with induced reversals. GABA was required to induce, and FLP-11 neuropeptides were required to sustain locomotion stop. RIS attenuates neuronal activity and inhibits movement, possibly enabling sensory integration and decision making, and exemplifies dual use of one cell across development in a compact nervous system.}, language = {en} } @article{StichtWeinreich2023, author = {Sticht, Oliver and Weinreich, Melina}, title = {Obdach, Speisung und Heilung. Zur Geschichte des Seelhauses an der Juliuspromenade in W{\"u}rzburg}, series = {W{\"u}rzburger Di{\"o}zesangeschichtsbl{\"a}tter}, volume = {86}, journal = {W{\"u}rzburger Di{\"o}zesangeschichtsbl{\"a}tter}, issn = {0342-3093}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361319}, pages = {359-375}, year = {2023}, abstract = {Das 1379 gestiftete Seelhaus befindet sich seit 1587 an der heutigen Juliuspromenade in W{\"u}rzburg. Urspr{\"u}nglich zur Beherbergung bed{\"u}rftiger Reisender eingerichtet, entwickelte es sich seit dem 17. Jahrhundert zum Alterssitz f{\"u}r M{\"a}gde und Hausangestellte, bevor es im 19. Jahrhundert ganz aufgel{\"o}st wurde. Durch den Kauf der Hausnummern 9-11 durch die Oberzeller Schwestern 1927 erlebte sein karitativer Auftrag bis zur Zerst{\"o}rung am 16. M{\"a}rz 1945 eine Wiederbelebung.}, subject = {Seelhaus W{\"u}rzburg}, language = {de} } @article{HellerReiterLeichtetal.2023, author = {Heller, Bianca and Reiter, Florian P. and Leicht, Hans Benno and Fiessler, Cornelia and Bergheim, Ina and Heuschmann, Peter U. and Geier, Andreas and Rau, Monika}, title = {Salt-intake-related behavior varies between sexes and is strongly associated with daily salt consumption in obese patients at high risk for MASLD}, series = {Nutrients}, volume = {15}, journal = {Nutrients}, number = {18}, issn = {2072-6643}, doi = {10.3390/nu15183942}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363107}, year = {2023}, abstract = {Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) imposes a significant burden on Westernized regions. The Western diet, high in salt intake, significantly contributes to disease development. However, there are a lack of data on salt literacy and salt intake among MASLD patients in Germany. Our study aims to analyze daily salt intake and salt-intake-related behavior in MASLD patients. Methods: 234 MASLD patients were prospectively included. Daily salt intake and salt-intake-related behavior were assessed via a food frequency questionnaire (FFQ—DEGS) and a salt questionnaire (SINU). Statistical analyses were performed using SPSS. Results: Mean daily salt intake was higher in men than in women (7.3 ± 5 g/d vs. 5.3 ± 4 g/d; p \< 0.001). There was significant agreement between increased daily salt intake (6 g/d) and the behavioral salt index (SI) (p \< 0.001). Men exhibited higher SI scores compared to women, indicating lower awareness of salt in everyday life. Multivariate analysis identified specific salt-intake-related behaviors impacting daily salt consumption. Conclusions: Our study reveals a strong link between daily salt intake and salt-intake-related behavior, highlighting sex-specific differences in an MASLD cohort. To enhance patient care in high-cardiovascular-risk populations, specific behavioral approaches may be considered, including salt awareness, to improve adherence to lifestyle changes, particularly in male patients.}, language = {en} } @article{WinterSchulzSchmitteretal.2023, author = {Winter, Anna and Schulz, Stefan M. and Schmitter, Marc and M{\"u}ller-Richter, Urs and K{\"u}bler, Alexander and Kasper, Sylvia and Hartmann, Stefan}, title = {Comprehensive geriatric assessment and quality of life aspects in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)}, series = {Journal of Clinical Medicine}, volume = {12}, journal = {Journal of Clinical Medicine}, number = {17}, issn = {2077-0383}, doi = {10.3390/jcm12175738}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363096}, year = {2023}, abstract = {To define frailty in older cancer patients, the aim of this study was to assess the geriatric status and quality of life (QoL) aspects in patients suffering from recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) under palliative treatment. A comprehensive geriatric assessment (CGA) was performed on 21 r/m HNSCC patients at two defined assessments, and the QoL aspects and the impact of descriptive data were evaluated. The Kolmogorov-Smirnov test, Spearman's rho correlation, and two-way mixed ANOVA were used for statistical analysis. All patients were found to be "frail". Pain, fatigue, and the burden of illness were the highest-rated symptoms. Oral function and orofacial appearance were highly impaired. A significant impact of descriptive data on the CGA and QoL results was found (all p ≤ 0.05). Thus, the CGA results revealed high frailty, severe comorbidities, and high impairments in QoL aspects. The CGA and QoL results were negatively affected by the primary HNSCC treatment approach, the need for prosthetic treatment, and worse oral functional capacity. Therefore, frailty in r/m HNSCC patients seems to be multidimensional. The evaluation of the CGA and QoL aspects in r/m HNSCC patients can be recommended to detect special needs, organize aftercare, and improve the support for frail and vulnerable cancer patients to create a multidisciplinary treatment approach.}, language = {en} } @article{CiuchiDiSanteDobrosavljevićetal.2018, author = {Ciuchi, Sergio and Di Sante, Domenico and Dobrosavljević, Vladimir and Fratini, Simone}, title = {The origin of Mooij correlations in disordered metals}, series = {npj Quantum Materials}, volume = {3}, journal = {npj Quantum Materials}, doi = {10.1038/s41535-018-0119-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223148}, year = {2018}, abstract = {Sufficiently disordered metals display systematic deviations from the behavior predicted by semi-classical Boltzmann transport theory. Here the scattering events from impurities or thermal excitations can no longer be considered as additive-independent processes, as asserted by Matthiessen's rule following from this picture. In the intermediate region between the regime of good conduction and that of insulation, one typically finds a change of sign of the temperature coefficient of resistivity, even at elevated temperature spanning ambient conditions, a phenomenology that was first identified by Mooij in 1973. Traditional weak coupling approaches to identify relevant corrections to the Boltzmann picture focused on long-distance interference effects such as "weak localization", which are especially important in low dimensions (1D and 2D) and close to the zero-temperature limit. Here we formulate a strong-coupling approach to tackle the interplay of strong disorder and lattice deformations (phonons) in bulk three-dimensional metals at high temperatures. We identify a polaronic mechanism of strong disorder renormalization, which describes how a lattice locally responds to the relevant impurity potential. This mechanism, which quantitatively captures the Mooij regime, is physically distinct and unrelated to Anderson localization, but realizes early seminal ideas of Anderson himself, concerning the interplay of disorder and lattice deformations.}, language = {en} } @article{SchneiderSeebauerBeuerleetal.2024, author = {Schneider, Tilman and Seebauer, Florian and Beuerle, Florian and W{\"u}rthner, Frank}, title = {A monodisperse, end-capped Ru(bda) oligomer with outstanding performance in heterogeneous electrochemical water oxidation}, series = {Advanced Materials Technologies}, volume = {9}, journal = {Advanced Materials Technologies}, number = {11}, issn = {2365-709X}, doi = {10.1002/admt.202301721}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363133}, year = {2024}, abstract = {AbstractWater oxidation catalysis is a key step for sustainable fuel production by water splitting into hydrogen and oxygen. The synthesis of a novel coordination oligomer based on four Ru(bda) (bda = 2,2′-bipyridine-6,6′-dicarboxylate) centers, three 4,4′-bipyridine (4,4′-bpy) linkers, and two 4-picoline (4-pic) end caps is reported. The monodispersity of this tetranuclear compound is characterized by NMR techniques. Heterogeneous electrochemical water oxidation after immobilization on multi-walled carbon nanotubes (MWCNTs) shows catalytic performance unprecedented for this compound class, with a turnover frequency (TOF) of 133 s\(^{-1}\) and a turnover number (TON) of 4.89 × 10\(^6\), at a current density of 43.8 mA cm\(^{-2}\) and a potential of 1.45 V versus normal hydrogen electrode (NHE).}, language = {en} } @article{BucheltBloetheKuenzeretal.2023, author = {Buchelt, Sebastian and Bl{\"o}the, Jan Henrik and Kuenzer, Claudia and Schmitt, Andreas and Ullmann, Tobias and Philipp, Marius and Kneisel, Christof}, title = {Deciphering small-scale seasonal surface dynamics of rock glaciers in the Central European Alps using DInSAR time series}, series = {Remote Sensing}, volume = {15}, journal = {Remote Sensing}, number = {12}, issn = {2072-4292}, doi = {10.3390/rs15122982}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362939}, year = {2023}, abstract = {The Essential Climate Variable (ECV) Permafrost is currently undergoing strong changes due to rising ground and air temperatures. Surface movement, forming characteristic landforms such as rock glaciers, is one key indicator for mountain permafrost. Monitoring this movement can indicate ongoing changes in permafrost; therefore, rock glacier velocity (RGV) has recently been added as an ECV product. Despite the increased understanding of rock glacier dynamics in recent years, most observations are either limited in terms of the spatial coverage or temporal resolution. According to recent studies, Sentinel-1 (C-band) Differential SAR Interferometry (DInSAR) has potential for monitoring RGVs at high spatial and temporal resolutions. However, the suitability of DInSAR for the detection of heterogeneous small-scale spatial patterns of rock glacier velocities was never at the center of these studies. We address this shortcoming by generating and analyzing Sentinel-1 DInSAR time series over five years to detect small-scale displacement patterns of five high alpine permafrost environments located in the Central European Alps on a weekly basis at a range of a few millimeters. Our approach is based on a semi-automated procedure using open-source programs (SNAP, pyrate) and provides East-West displacement and elevation change with a ground sampling distance of 5 m. Comparison with annual movement derived from orthophotos and unpiloted aerial vehicle (UAV) data shows that DInSAR covers about one third of the total movement, which represents the proportion of the year suited for DInSAR, and shows good spatial agreement (Pearson R: 0.42-0.74, RMSE: 4.7-11.6 cm/a) except for areas with phase unwrapping errors. Moreover, the DInSAR time series unveils spatio-temporal variations and distinct seasonal movement dynamics related to different drivers and processes as well as internal structures. Combining our approach with in situ observations could help to achieve a more holistic understanding of rock glacier dynamics and to assess the future evolution of permafrost under changing climatic conditions.}, language = {en} } @article{BruennertSeupelGoyaletal.2023, author = {Br{\"u}nnert, Daniela and Seupel, Raina and Goyal, Pankaj and Bach, Matthias and Schraud, Heike and Kirner, Stefanie and K{\"o}ster, Eva and Feineis, Doris and Bargou, Ralf C. and Schlosser, Andreas and Bringmann, Gerhard and Chatterjee, Manik}, title = {Ancistrocladinium A induces apoptosis in proteasome inhibitor-resistant multiple myeloma cells: a promising therapeutic agent candidate}, series = {Pharmaceuticals}, volume = {16}, journal = {Pharmaceuticals}, number = {8}, issn = {1424-8247}, doi = {10.3390/ph16081181}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362887}, year = {2023}, abstract = {The N,C-coupled naphthylisoquinoline alkaloid ancistrocladinium A belongs to a novel class of natural products with potent antiprotozoal activity. Its effects on tumor cells, however, have not yet been explored. We demonstrate the antitumor activity of ancistrocladinium A in multiple myeloma (MM), a yet incurable blood cancer that represents a model disease for adaptation to proteotoxic stress. Viability assays showed a potent apoptosis-inducing effect of ancistrocladinium A in MM cell lines, including those with proteasome inhibitor (PI) resistance, and in primary MM cells, but not in non-malignant blood cells. Concomitant treatment with the PI carfilzomib or the histone deacetylase inhibitor panobinostat strongly enhanced the ancistrocladinium A-induced apoptosis. Mass spectrometry with biotinylated ancistrocladinium A revealed significant enrichment of RNA-splicing-associated proteins. Affected RNA-splicing-associated pathways included genes involved in proteotoxic stress response, such as PSMB5-associated genes and the heat shock proteins HSP90 and HSP70. Furthermore, we found strong induction of ATF4 and the ATM/H2AX pathway, both of which are critically involved in the integrated cellular response following proteotoxic and oxidative stress. Taken together, our data indicate that ancistrocladinium A targets cellular stress regulation in MM and improves the therapeutic response to PIs or overcomes PI resistance, and thus may represent a promising potential therapeutic agent.}, language = {en} } @article{EidmannHeinzOberfeldetal.2023, author = {Eidmann, Annette and Heinz, Tizian and Oberfeld, Jan and Weißenberger, Manuel and Rudert, Maximilian and Stratos, Ioannis}, title = {Epidemiology and trends in cartilage surgery of the foot and ankle in Germany: an analysis of national healthcare billing and reporting data from 2006 to 2020}, series = {Medicina}, volume = {59}, journal = {Medicina}, number = {7}, issn = {1648-9144}, doi = {10.3390/medicina59071256}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362835}, year = {2023}, abstract = {Background and objectives: Cartilage surgery constitutes a standard intervention in foot and ankle procedures. Currently, there is a lack of epidemiological data on its frequency, age distribution, and surgical options for cartilage surgery. This study aimed to investigate the current landscape of cartilage surgery in Germany and identify the most common procedures from an epidemiological standpoint. Materials and methods: Medical billing and reporting data from the Federal Statistical Office of Germany, encompassing the period 2006-2020, was examined, including all foot and ankle cartilage surgical procedures (summarized under OPS codes 5-812 and 5-801). The dataset incorporated information on the affected joint, patient age and sex, and surgery type. Each surgical procedure was categorized as "debridement", "regeneration" or "refixation". Linear and nonlinear regression analyses were employed, with a statistical significance threshold of 0.05. Results: From the total of 136,501 procedures conducted during the study period, the most frequently performed interventions were microfracture (58,252) and chondroplasty (56,135), and thus, debridement procedures were in the leading position. The use of acellular membranes was the most used regenerative technique (n = 11,414). At the ankle joint, interventions were mostly arthroscopic and in men, while foot cartilage surgeries were preferably performed via open surgery and mostly in women. Age distribution analysis revealed two primary peaks: the first in the 20-25-year-old group (ankle and foot) and the second in the 45-50-year-old group (ankle) and 55-60-year-old group (foot). Refixation and regenerative procedures were more frequent among younger individuals, while debriding procedures were more frequent among older individuals. Regenerative procedures, particularly in the ankle, significantly increased over time. Conclusions: Cartilage surgery of the foot and ankle was common, with two primary age groups predominantly affected. Notably, recent years have witnessed a considerable rise in cartilage regenerative procedures.}, language = {en} } @article{EwaldFuchsBoegeleinetal.2023, author = {Ewald, Andrea and Fuchs, Andreas and Boegelein, Lasse and Grunz, Jan-Peter and Kneist, Karl and Gbureck, Uwe and Hoelscher-Doht, Stefanie}, title = {Degradation and bone-contact biocompatibility of two drillable magnesium phosphate bone cements in an in vivo rabbit bone defect model}, series = {Materials}, volume = {16}, journal = {Materials}, number = {13}, issn = {1996-1944}, doi = {10.3390/ma16134650}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362824}, year = {2023}, abstract = {The use of bone-cement-enforced osteosynthesis is a growing topic in trauma surgery. In this context, drillability is a desirable feature for cements that can improve fracture stability, which most of the available cement systems lack. Therefore, in this study, we evaluated a resorbable and drillable magnesium-phosphate (MgP)-based cement paste considering degradation behavior and biocompatibility in vivo. Two different magnesium-phosphate-based cement (MPC) pastes with different amounts of phytic acid (IP 6) as setting retarder (MPC 22.5 and MPC 25) were implanted in an orthotopic defect model of the lateral femoral condyle of New Zealand white rabbits for 6 weeks. After explantation, their resorption behavior and material characteristics were evaluated by means of X-ray diffraction (XRD), porosimetry measurement, histological staining, peripheral quantitative computed tomography (pQCT), cone-beam computed tomography (CBCT) and biomechanical load-to-failure tests. Both cement pastes displayed comparable results in mechanical strength and resorption kinetics. Bone-contact biocompatibility was excellent without any signs of inflammation. Initial resorption and bone remodeling could be observed. MPC pastes with IP 6 as setting retardant have the potential to be a valuable alternative in distinct fracture patterns. Drillability, promising resorption potential and high mechanical strength confirm their suitability for use in clinical routine.}, language = {en} } @article{HartmannKnierimMaureretal.2023, author = {Hartmann, Nico and Knierim, Maria and Maurer, Wiebke and Dybkova, Nataliya and Hasenfuß, Gerd and Sossalla, Samuel and Streckfuss-B{\"o}meke, Katrin}, title = {Molecular and functional relevance of Na\(_V\)1.8-induced atrial arrhythmogenic triggers in a human SCN10A knock-out stem cell model}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {12}, issn = {1422-0067}, doi = {10.3390/ijms241210189}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362708}, year = {2023}, abstract = {In heart failure and atrial fibrillation, a persistent Na\(^+\) current (I\(_{NaL}\)) exerts detrimental effects on cellular electrophysiology and can induce arrhythmias. We have recently shown that Na\(_V\)1.8 contributes to arrhythmogenesis by inducing a I\(_{NaL}\). Genome-wide association studies indicate that mutations in the SCN10A gene (Na\(_V\)1.8) are associated with increased risk for arrhythmias, Brugada syndrome, and sudden cardiac death. However, the mediation of these Na\(_V\)1.8-related effects, whether through cardiac ganglia or cardiomyocytes, is still a subject of controversial discussion. We used CRISPR/Cas9 technology to generate homozygous atrial SCN10A-KO-iPSC-CMs. Ruptured-patch whole-cell patch-clamp was used to measure the I\(_{NaL}\) and action potential duration. Ca\(^{2+}\) measurements (Fluo 4-AM) were performed to analyze proarrhythmogenic diastolic SR Ca\(^{2+}\) leak. The I\(_{NaL}\) was significantly reduced in atrial SCN10A KO CMs as well as after specific pharmacological inhibition of Na\(_V\)1.8. No effects on atrial APD\(_{90}\) were detected in any groups. Both SCN10A KO and specific blockers of Na\(_V\)1.8 led to decreased Ca\(^{2+}\) spark frequency and a significant reduction of arrhythmogenic Ca\(^{2+}\) waves. Our experiments demonstrate that Na\(_V\)1.8 contributes to I\(_{NaL}\) formation in human atrial CMs and that Na\(_V\)1.8 inhibition modulates proarrhythmogenic triggers in human atrial CMs and therefore Na\(_V\)1.8 could be a new target for antiarrhythmic strategies.}, language = {en} } @article{HeinzWildEidmannetal.2023, author = {Heinz, Tizian and Wild, Moritz and Eidmann, Annette and Weißenberger, Manuel and Rak, Dominik and Nedopil, Alexander Johannes and Rudert, Maximilian and Stratos, Ioannis}, title = {Impact of COVID-19 on fracture incidence in germany: a comparative age and gender analysis of pre- and post-outbreak periods}, series = {Healthcare}, volume = {11}, journal = {Healthcare}, number = {15}, issn = {2227-9032}, doi = {10.3390/healthcare11152139}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362686}, year = {2023}, abstract = {In March 2020, Germany imposed a nationwide lockdown to curb the spread of COVID-19, prompting questions about the impact on the incidence of common fractures. This study examined 15 fracture types in pre-outbreak (2010-2019) and post-outbreak (2020-2021) periods, using data categorized by age (18-64 years, 65 years) and sex (male, female). Linear regression assessed annual growth rates, and mean fracture numbers were compared across periods for significant differences. Results indicated a positive correlation between fracture incidence rates and time for various types, such as cervical, thoracic, lumbar, and pelvic spine fractures, rib fractures, femoral neck, pertrochanteric femur, femoral shaft, and ankle fractures. Frequencies of proximal humerus, distal radius, femoral neck, pertrochanteric femur, femoral shaft, and ankle fractures in 2020 and 2021 were within predicted ranges from previous years. However, rib fractures and spinal fractures (cervical, thoracic, lumbar, and pelvic spine) occurred less frequently during this time. Notably, this study found a consistent decline in most fracture types for individuals aged 18-64 after the pandemic's onset, while the fracture incidence of hip fractures, often referred to as fragility fractures, for those over 65 remained unchanged. Fibula fractures showed the most considerable decrease in both age groups. In conclusion, the COVID-19 pandemic substantially impacted fracture incidence, with lower rates among individuals under 65 and unchanged fragility fractures in the elderly population.}, language = {en} } @article{SchuergerEngel2023, author = {Sch{\"u}rger, Peter and Engel, Volker}, title = {Differential Shannon entropies characterizing electron-nuclear dynamics and correlation: momentum-space versus coordinate-space wave packet motion}, series = {Entropy}, volume = {25}, journal = {Entropy}, number = {7}, issn = {1099-4300}, doi = {10.3390/e25070970}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362670}, year = {2023}, abstract = {We calculate differential Shannon entropies derived from time-dependent coordinate-space and momentum-space probability densities. This is performed for a prototype system of a coupled electron-nuclear motion. Two situations are considered, where one is a Born-Oppenheimer adiabatic dynamics, and the other is a diabatic motion involving strong non-adiabatic transitions. The information about coordinate- and momentum-space dynamics derived from the total and single-particle entropies is discussed and interpreted with the help of analytical models. From the entropies, we derive mutual information, which is a measure for the electron-nuclear correlation. In the adiabatic case, it is found that such correlations are manifested differently in coordinate- and momentum space. For the diabatic dynamics, we show that it is possible to decompose the entropies into state-specific contributions.}, language = {en} } @article{ElsnerKunzWagneretal.2023, author = {Elsner, Clara and Kunz, Andreas Steven and Wagner, Nicole and Huflage, Henner and H{\"u}bner, Stefan and Luetkens, Karsten Sebastian and Bley, Thorsten Alexander and Schmitt, Rainer and Erg{\"u}n, S{\"u}leyman and Grunz, Jan-Peter}, title = {MRI-based evaluation of the flexor digitorum superficialis anatomy: investigating the prevalence and morphometry of the "chiasma antebrachii"}, series = {Diagnostics}, volume = {13}, journal = {Diagnostics}, number = {14}, issn = {2075-4418}, doi = {10.3390/diagnostics13142406}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362631}, year = {2023}, abstract = {Recent dissection studies resulted in the introduction of the term "chiasma antebrachii", which represents an intersection of the flexor digitorum superficialis (FDS) tendons for digits 2 and 3 in the distal third of the forearm. This retrospective investigation aimed to provide an MRI-based morphologic analysis of the chiasma antebrachii. In 89 patients (41 women, 39.3 ± 21.3 years), MRI examinations of the forearm (2010-2021) were reviewed by two radiologists, who evaluated all studies for the presence and length of the chiasma as well as its distance from the distal radioulnar and elbow joint. The chiasma antebrachii was identified in the distal third of the forearm in 88 patients (98.9\%), while one intersection was located more proximally in the middle part. The chiasma had a median length of 28 mm (interquartile range: 24-35 mm). Its distances to the distal radioulnar and elbow joint were 16 mm (8-25 mm) and 215 mm (187-227 mm), respectively. T1-weighted post-contrast sequences were found to be superior to T2- or proton-density-weighted sequences in 71 cases (79.8\%). To conclude, the chiasma antebrachii is part of the standard FDS anatomy. Knowledge of its morphology is important, e.g., in targeted injections of therapeutics or reconstructive surgery.}, language = {en} } @article{LuetkensGrunzKunzetal.2023, author = {Luetkens, Karsten Sebastian and Grunz, Jan-Peter and Kunz, Andreas Steven and Huflage, Henner and Weißenberger, Manuel and Hartung, Viktor and Patzer, Theresa Sophie and Gruschwitz, Philipp and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Feldle, Philipp}, title = {Ultra-high-resolution photon-counting detector CT arthrography of the ankle: a feasibility study}, series = {Diagnostics}, volume = {13}, journal = {Diagnostics}, number = {13}, issn = {2075-4418}, doi = {10.3390/diagnostics13132201}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362622}, year = {2023}, abstract = {This study was designed to investigate the image quality of ultra-high-resolution ankle arthrography employing a photon-counting detector CT. Bilateral arthrograms were acquired in four cadaveric specimens with full-dose (10 mGy) and low-dose (3 mGy) scan protocols. Three convolution kernels with different spatial frequencies were utilized for image reconstruction (ρ\(_{50}\); Br98: 39.0, Br84: 22.6, Br76: 16.5 lp/cm). Seven radiologists subjectively assessed the image quality regarding the depiction of bone, hyaline cartilage, and ligaments. An additional quantitative assessment comprised the measurement of noise and the computation of contrast-to-noise ratios (CNR). While an optimal depiction of bone tissue was achieved with the ultra-sharp Br98 kernel (S ≤ 0.043), the visualization of cartilage improved with lower modulation transfer functions at each dose level (p ≤ 0.014). The interrater reliability ranged from good to excellent for all assessed tissues (intraclass correlation coefficient ≥ 0.805). The noise levels in subcutaneous fat decreased with reduced spatial frequency (p \< 0.001). Notably, the low-dose Br76 matched the CNR of the full-dose Br84 (p 0.999) and superseded Br98 (p \< 0.001) in all tissues. Based on the reported results, a photon-counting detector CT arthrography of the ankle with an ultra-high-resolution collimation offers stellar image quality and tissue assessability, improving the evaluation of miniscule anatomical structures. While bone depiction was superior in combination with an ultra-sharp convolution kernel, soft tissue evaluation benefited from employing a lower spatial frequency.}, language = {en} } @article{BreunFlockFeldheimetal.2023, author = {Breun, Maria and Flock, Katharina and Feldheim, Jonas and Nattmann, Anja and Monoranu, Camelia M. and Herrmann, Pia and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten and Stein, Ulrike}, title = {Metastasis associated in colorectal cancer 1 (MACC1) mRNA expression is enhanced in sporadic vestibular schwannoma and correlates to deafness}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {16}, issn = {2072-6694}, doi = {10.3390/cancers15164089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362543}, year = {2023}, abstract = {Vestibular schwannoma (VS) are benign cranial nerve sheath tumors of the vestibulocochlear nerve. Their incidence is mostly sporadic, but they can also be associated with NF2-related schwannomatosis (NF2), a hereditary tumor syndrome. Metastasis associated in colon cancer 1 (MACC1) is known to contribute to angiogenesis, cell growth, invasiveness, cell motility and metastasis of solid malignant cancers. In addition, MACC1 may be associated with nonsyndromic hearing impairment. Therefore, we evaluated whether MACC1 may be involved in the pathogenesis of VS. Sporadic VS, recurrent sporadic VS, NF2-associated VS, recurrent NF2-associated VS and healthy vestibular nerves were analyzed for MACC1 mRNA and protein expression by quantitative polymerase chain reaction and immunohistochemistry. MACC1 expression levels were correlated with the patients' clinical course and symptoms. MACC1 mRNA expression was significantly higher in sporadic VS compared to NF2-associated VS (p \< 0.001). The latter expressed similar MACC1 concentrations as healthy vestibular nerves. Recurrent tumors resembled the MACC1 expression of the primary tumors. MACC1 mRNA expression was significantly correlated with deafness in sporadic VS patients (p = 0.034). Therefore, MACC1 might be a new molecular marker involved in VS pathogenesis.}, language = {en} } @article{GrunzKunzBaumannetal.2023, author = {Grunz, Jan-Peter and Kunz, Andreas Steven and Baumann, Freerk T. and Hasenclever, Dirk and Sieren, Malte Maria and Heldmann, Stefan and Bley, Thorsten Alexander and Einsele, Hermann and Knop, Stefan and Jundt, Franziska}, title = {Assessing osteolytic lesion size on sequential CT scans is a reliable study endpoint for bone remineralization in newly diagnosed multiple myeloma}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {15}, issn = {2072-6694}, doi = {10.3390/cancers15154008}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362526}, year = {2023}, abstract = {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.}, language = {en} } @article{WatzlingKlausWeidemeieretal.2023, author = {Watzling, Martin and Klaus, Lorenz and Weidemeier, Tamara and Horder, Hannes and Ebert, Regina and Blunk, Torsten and Bauer-Kreisel, Petra}, title = {Three-dimensional breast cancer model to investigate CCL5/CCR1 expression mediated by direct contact between breast cancer cells and adipose-derived stromal cells or adipocytes}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {13}, issn = {2072-6694}, doi = {10.3390/cancers15133501}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362502}, year = {2023}, abstract = {The tumor microenvironment (TME) in breast cancer is determined by the complex crosstalk of cancer cells with adipose tissue-inherent cells such as adipose-derived stromal cells (ASCs) and adipocytes resulting from the local invasion of tumor cells in the mammary fat pad. This leads to heterotypic cellular contacts between these cell types. To adequately mimic the specific cell-to-cell interaction in an in vivo-like 3D environment, we developed a direct co-culture spheroid model using ASCs or differentiated adipocytes in combination with MDA-MB-231 or MCF-7 breast carcinoma cells. Co-spheroids were generated in a well-defined and reproducible manner in a high-throughput process. We compared the expression of the tumor-promoting chemokine CCL5 and its cognate receptors in these co-spheroids to indirect and direct standard 2D co-cultures. A marked up-regulation of CCL5 and in particular the receptor CCR1 with strict dependence on cell-cell contacts and culture dimensionality was evident. Furthermore, the impact of direct contacts between ASCs and tumor cells and the involvement of CCR1 in promoting tumor cell migration were demonstrated. Overall, these results show the importance of direct 3D co-culture models to better represent the complex tumor-stroma interaction in a tissue-like context. The unveiling of tumor-specific markers that are up-regulated upon direct cell-cell contact with neighboring stromal cells, as demonstrated in the 3D co-culture spheroids, may represent a promising strategy to find new targets for the diagnosis and treatment of invasive breast cancer.}, language = {en} } @article{HiewEibeckNguemenietal.2023, author = {Hiew, Shawn and Eibeck, Leila and Nguemeni, Carine and Zeller, Daniel}, title = {The influence of age and physical activity on locomotor adaptation}, series = {Brain Sciences}, volume = {13}, journal = {Brain Sciences}, number = {9}, issn = {2076-3425}, doi = {10.3390/brainsci13091266}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362478}, year = {2023}, abstract = {Background: Aging increases individual susceptibility to falls and injuries, suggesting poorer adaptation of balance responses to perturbation during locomotion, which can be measured with the locomotor adaptation task (LAT). However, it is unclear how aging and lifestyle factors affect these responses during walking. Hence, the present study investigates the relationship between balance and lifestyle factors during the LAT in healthy individuals across the adult lifespan using a correlational design. Methods: Thirty participants aged 20-78 years performed an LAT on a split-belt treadmill (SBT). We evaluated the magnitude and rate of adaptation and deadaptation during the LAT. Participants reported their lifelong physical and cognitive activity. Results: Age positively correlated with gait-line length asymmetry at the late post-adaptation phase (p = 0.007). These age-related effects were mediated by recent physical activity levels (p = 0.040). Conclusion: Our results confirm that locomotor adaptive responses are preserved in aging, but the ability to deadapt newly learnt balance responses is compromised with age. Physical activity mediates these age-related effects. Therefore, gait symmetry post-adaptation could effectively measure the risk of falling, and maintaining physical activity could protect against declines in balance.}, language = {en} } @article{GuederReinFlohretal.2023, author = {G{\"u}der, G{\"u}lmisal and Rein, Eva von and Flohr, Thomas and Weismann, Dirk and Schmitt, Dominik and St{\"o}rk, Stefan and Frantz, Stefan and Kratzer, Vincent and Kendi, Christian}, title = {Motion detectors as additional monitoring devices in the intensive care unit — a proof-of-concept study}, series = {Applied Sciences}, volume = {13}, journal = {Applied Sciences}, number = {16}, issn = {2076-3417}, doi = {10.3390/app13169319}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362404}, year = {2023}, abstract = {Background: Monitoring the vital signs of delirious patients in an intensive care unit (ICU) is challenging, as they might (un-)intentionally remove devices attached to their bodies. In mock-up scenarios, we systematically assessed whether a motion detector (MD) attached to the bed may help in identifying emergencies. Methods: We recruited 15 employees of the ICU and equipped an ICU bed with an MD (IRON Software GmbH, Gr{\"u}nwald, Germany). Participants were asked to replay 22 mock-up scenes of one-minute duration each: 12 scenes with movements and 10 without movements, of which 5 were emergency scenes ("lying dead-still, with no or very shallow breathing"). Blinded recordings were presented to an evaluation panel consisting of an experienced ICU nurse and a physician, who was asked to assess and rate the presence of motions. Results: Fifteen participants (nine women; 173 ± 7.0 cm; 78 ± 19 kg) joined the study. In total, 286 out of 330 scenes (86.7\%) were rated correctly. Ratings were false negative (FN: "no movements detected, but recorded") in 7 out of 180 motion scenes (3.9\%). Ratings were false positive (FP: "movements detected, but not recorded") in 37 out of 150 scenes (24.7\%), more often in men than women (26 out of 60 vs. 11 out of 90, respectively; p \< 0.001). Of note, in 16 of these 37 FP-rated scenes, a vibrating mobile phone was identified as a potential confounder. The emergency scenes were correctly rated in 64 of the 75 runs (85.3\%); 10 of the 11 FP-rated scenes occurred in male subjects. Conclusions: The MD allowed for identifying motions of test subjects with high sensitivity (96\%) and acceptable specificity (75\%). Accuracy might increase further if activities are recorded continuously under real-world conditions.}, language = {en} } @article{OdorferVolkmann2023, author = {Odorfer, Thorsten M. and Volkmann, Jens}, title = {Deep brain stimulation for focal or segmental craniocervical dystonia in patients who have failed botulinum neurotoxin therapy - a narrative review of the literature}, series = {Toxins}, volume = {15}, journal = {Toxins}, number = {10}, issn = {2072-6651}, doi = {10.3390/toxins15100606}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357707}, year = {2023}, abstract = {(1) Background: The first-line treatment for patients with focal or segmental dystonia with a craniocervical distribution is still the intramuscular injection of botulinum neurotoxin (BoNT). However, some patients experience primary or secondary treatment failure from this potential immunogenic therapy. Deep brain stimulation (DBS) may then be used as a backup strategy in this situation. (2) Methods: Here, we reviewed the current study literature to answer a specific question regarding the efficacy and safety of the use of DBS, particularly for cervical dystonia (CD) and Meige syndrome (MS) in patients with documented treatment failure under BoNT. (3) Results: There are only two studies with the highest level of evidence in this area. Despite this clear limitation, in the context of the narrowly defined research question of this paper, it is possible to report 161 patients with CD or MS who were included in studies that were able to show a statistically significant reduction in dystonic symptoms using DBS. Safety and tolerability data appeared adequate. However, much of the information is based on retrospective observations. (4) Conclusions: The evidence base in this area is in need of further scientific investigation. Most importantly, more randomized, controlled and double-blind trials are needed, possibly including a head-to-head comparison of DBS and BoNT.}, language = {en} } @article{MoratinThoeleLangetal.2023, author = {Moratin, Helena and Th{\"o}le, Anna and Lang, Josephine and Ehret Kasemo, Totta and St{\"o}th, Manuel and Hagen, Rudolf and Scherzad, Agmal and Hackenberg, Stephan}, title = {Ag- but not ZnO-nanoparticles disturb the airway epithelial barrier at subtoxic concentrations}, series = {Pharmaceutics}, volume = {15}, journal = {Pharmaceutics}, number = {10}, issn = {1999-4923}, doi = {10.3390/pharmaceutics15102506}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357403}, year = {2023}, abstract = {Inhalation is considered to be the most relevant source of human exposure to nanoparticles (NPs); however, only a few investigations have addressed the influence of exposing the respiratory mucosal barrier to subcytotoxic doses. In the nasal respiratory epithelium, cells of the mucosa represent one of the first contact points of the human organism with airborne NPs. Disruption of the epithelial barrier by harmful materials can lead to inflammation in addition to potential intrinsic toxicity of the particles. The aim of this study was to investigate whether subtoxic concentrations of zinc oxide (ZnO)- and silver (Ag)-NPs have an influence on upper airway barrier integrity. Nasal epithelial cells from 17 donors were cultured at the air-liquid interface and exposed to ZnO- and Ag-NPs. Barrier function, quantified by transepithelial electrical resistance (TEER), decreased after treatment with 10 µg/mL Ag-NPs, but FITC-dextran permeability remained stable and no change in mRNA levels of tight junction proteins and E-cadherin was detected by real-time quantitative PCR (RT-qPCR). The results indicate that subtoxic concentrations of Ag-NPs may already induce damage of the upper airway epithelial barrier in vitro. The lack of similar disruption by ZnO-NPs of similar size suggests a specific effect by Ag-NPs.}, language = {en} } @article{IsraelRiehlButtetal.2023, author = {Israel, Ina and Riehl, Gabriele and Butt, Elke and Buck, Andreas K. and Samnick, Samuel}, title = {Gallium-68-labeled KISS1-54 peptide for mapping KISS1 receptor via PET: initial evaluation in human tumor cell lines and in tumor-bearing mice}, series = {Pharmaceuticals}, volume = {17}, journal = {Pharmaceuticals}, number = {1}, issn = {1424-8247}, doi = {10.3390/ph17010044}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355898}, year = {2023}, abstract = {Kisspeptins (KPs, KISS1) and their receptor (KISS1R) play a pivotal role as metastasis suppressor for many cancers. Low or lost KP expression is associated with higher tumor grade, increased metastatic potential, and poor prognosis. Therefore, KP expression has prognostic relevance and correlates with invasiveness in cancers. Furthermore, KISS1R represents a very promising target for molecular imaging and therapy for KISS1R-expressing tumors. The goal of this study was to evaluate the developed KISS1-54 derivative, [\(^{68}\)Ga]KISS1-54, as a PET-imaging probe for KISS1R-expressing tumors. The NODAGA-KISS1-54 peptide was labeled by Gallium-68, and the stability of the resulting [\(^{68}\)Ga]KISS1-54 evaluated in injection solution and human serum, followed by an examination in different KISS1R-expressing tumor cell lines, including HepG2, HeLa, MDA-MB-231, MCF7, LNCap, SK-BR-3, and HCT116. Finally, [\(^{68}\)Ga]KISS1-54 was tested in LNCap- and MDA-MB-231-bearing mice, using µ-PET, assessing its potential as an imaging probe for PET. [\(^{68}\)Ga]KISS1-54 was obtained in a 77 ± 7\% radiochemical yield and at a >99\% purity. The [\(^{68}\)Ga]KISS1-54 cell uptake amounted to 0.6-4.4\% per 100,000 cells. Moreover, the accumulation of [\(^{68}\)Ga]KISS1-54 was effectively inhibited by nonradioactive KISS1-54. In [\(^{68}\)Ga]KISS1-54-PET, KISS1R-positive LNCap-tumors were clearly visualized as compared to MDA-MB-231-tumor implant with predominantly intracellular KISS1R expression. Our first results suggest that [\(^{68}\)Ga]KISS1-54 is a promising candidate for a radiotracer for targeting KISS1R-expressing tumors via PET.}, language = {en} } @article{MichalskiSchloetelburgHartrampfetal.2023, author = {Michalski, Kerstin and Schl{\"o}telburg, Wiebke and Hartrampf, Philipp E. and Kosmala, Aleksander and Buck, Andreas K. and Hahner, Stefanie and Schirbel, Andreas}, title = {Radiopharmaceuticals for treatment of adrenocortical carcinoma}, series = {Pharmaceuticals}, volume = {17}, journal = {Pharmaceuticals}, number = {1}, issn = {1424-8247}, doi = {10.3390/ph17010025}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355901}, year = {2023}, abstract = {Adrenocortical carcinoma (ACC) represents a rare tumor entity with limited treatment options and usually rapid tumor progression in case of metastatic disease. As further treatment options are needed and ACC metastases are sensitive to external beam radiation, novel theranostic approaches could complement established therapeutic concepts. Recent developments focus on targeting adrenal cortex-specific enzymes like the theranostic twin [\(^{123/131}\)I]IMAZA that shows a good image quality and a promising therapeutic effect in selected patients. But other established molecular targets in nuclear medicine such as the C-X-C motif chemokine receptor 4 (CXCR4) could possibly enhance the therapeutic regimen as well in a subgroup of patients. The aims of this review are to give an overview of innovative radiopharmaceuticals for the treatment of ACC and to present the different molecular targets, as well as to show future perspectives for further developments since a radiopharmaceutical with a broad application range is still warranted.}, language = {en} } @article{KimpelAltieriDischingeretal.2023, author = {Kimpel, Otilia and Altieri, Barbara and Dischinger, Ulrich and Fuss, Carmina Teresa and Kurlbaum, Max and Fassnacht, Martin}, title = {Early detection of recurrence and progress using serum steroid profiling by LC-MS/MS in patients with adrenocortical carcinoma}, series = {Metabolites}, volume = {14}, journal = {Metabolites}, number = {1}, issn = {2218-1989}, doi = {10.3390/metabo14010020}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355839}, year = {2023}, abstract = {Serum liquid chromatography-tandem mass spectrometry (LC-MS/MS) steroid profiling is used for the diagnosis of adrenocortical carcinoma (ACC). Guidelines recommend endocrine work-up in addition to radiological imaging for follow-up in ACC, but data on this topic are scarce. Patients were included in this retrospective study if pre-therapeutic hormone values, regular tumour evaluation by imaging, steroid measurements by LC-MS/MS, and details on therapies were available. The utility of steroid profiles in detecting recurrence or disease progression was assessed, whereby "endocrine progress" was defined by an elevation of at least 3 of 13 analysed hormones. Cohort A included 47 patients after R0 resection, of whom 15 experienced recurrence and 32 did not. In cohort B, 52 patients with advanced disease (including 7 patients of cohort A with recurrence) could be evaluated on 74 visits when progressive disease was documented. In 20 of 89 cases with documented disease progression, "endocrine progress" was detectable prior to radiological progress. In these cases, recurrence/progression was detected at a median of 32 days earlier by steroid measurement than by imaging, with 11-deoxycortisol and testosterone being the most sensitive markers. Notably, these patients had significantly larger tumour burden. In conclusion, steroid profiling by LC-MS/MS is of value in detecting recurrent/progressive disease in ACC.}, language = {en} } @article{EngertDollVonaetal.2023, author = {Engert, Jonas and Doll, Julia and Vona, Barbara and Ehret Kasemo, Totta and Spahn, Bjoern and Hagen, Rudolf and Rak, Kristen and Voelker, Johannes}, title = {mRNA abundance of neurogenic factors correlates with hearing capacity in auditory brainstem nuclei of the rat}, series = {Life}, volume = {13}, journal = {Life}, number = {9}, issn = {2075-1729}, doi = {10.3390/life13091858}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357392}, year = {2023}, abstract = {Neural stem cells (NSCs) have previously been described up to the adult stage in the rat cochlear nucleus (CN). A decreasing neurogenic potential was observed with critical changes around hearing onset. A better understanding of molecular factors affecting NSCs and neurogenesis is of interest as they represent potential targets to treat the cause of neurologically based hearing disorders. The role of genes affecting NSC development and neurogenesis in CN over time on hearing capacity has remained unclear. This study investigated the mRNA abundance of genes influencing NSCs and neurogenesis in rats' CN over time. The CN of rats on postnatal days 6, 12, and 24 were examined. Real-time quantitative polymerase chain reaction arrays were used to compare mRNA levels of 84 genes relevant to NSCs and neurogenesis. Age- and hearing-specific patterns of changes in mRNA abundance of neurogenically relevant genes were detected in the rat CN. Additionally, crucial neurogenic factors with significant and relevant influence on neurogenesis were identified. The results of this work should contribute to a better understanding of the molecular mechanisms underlying the neurogenesis of the auditory pathway.}, language = {en} } @article{SteinhardtCejkaChenetal.2024, author = {Steinhardt, Maximilian J. and Cejka, Vladimir and Chen, Mengmeng and B{\"a}uerlein, Sabrina and Sch{\"a}fer, Julia and Adrah, Ali and Ihne-Schubert, Sandra M. and Papagianni, Aikaterini and Kort{\"u}m, K. Martin and Morbach, Caroline and St{\"o}rk, Stefan}, title = {Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study}, series = {Journal of Clinical Medicine}, volume = {13}, journal = {Journal of Clinical Medicine}, number = {1}, issn = {2077-0383}, doi = {10.3390/jcm13010283}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-356024}, year = {2024}, abstract = {Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1\% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5\% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.}, language = {en} } @article{SperlichMatzkaHolmberg2023, author = {Sperlich, Billy and Matzka, Manuel and Holmberg, Hans-Christer}, title = {The proportional distribution of training by elite endurance athletes at different intensities during different phases of the season}, series = {Frontiers in Sports and Active Living}, volume = {5}, journal = {Frontiers in Sports and Active Living}, doi = {10.3389/fspor.2023.1258585}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357988}, year = {2023}, abstract = {The present review examines retrospective analyses of training intensity distribution (TID), i.e., the proportion of training at moderate (Zone 1, Z1), heavy (Z2) and severe (Z3) intensity by elite-to-world-class endurance athletes during different phases of the season. In addition, we discuss potential implications of our findings for research in this field, as well as for training by these athletes. Altogether, we included 175 TIDs, of which 120 quantified exercise intensity on the basis of heart rate and measured time-in-zone or employed variations of the session goal approach, with demarcation of zones of exercise intensity based on physiological parameters. Notably, 49\% of the TIDs were single-case studies, predominantly concerning cross-country skiing and/or the biathlon. Eighty-nine TIDs were pyramidal (Z1 > Z2 > Z3), 65 polarized (Z1 > Z3 > Z2) and 8 "threshold" (Z2 > Z1 = Z3). However, these relative numbers varied between sports and the particular phases of the season. In 91\% (n = 160) of the TIDs >60\% of the endurance exercise was of low intensity. Regardless of the approach to quantification or phase of the season, cyclists and swimmers were found to perform a lower proportion of exercise in Z1 (<72\%) and higher proportion in Z2 (>16\%) than athletes involved in the triathlon, speed skating, rowing, running, cross-country skiing or biathlon (>80\% in Z1 and <12\% in Z2 in all these cases). For most of the athletes their proportion of heavy-to-severe exercise was higher during the period of competition than during the preparatory phase, although with considerable variability between sports. In conclusion, the existing literature in this area does not allow general conclusions to be drawn. The methods utilized for quantification vary widely and, moreover, contextual information concerning the mode of exercise, environmental conditions, and biomechanical aspects of the exercise is often lacking. Therefore, we recommend a more comprehensive approach in connection with future investigations on the TIDs of athletes involved in different endurance sports.}, language = {en} } @article{SperlichDuekingLeppichetal.2023, author = {Sperlich, Billy and D{\"u}king, Peter and Leppich, Robert and Holmberg, Hans-Christer}, title = {Strengths, weaknesses, opportunities, and threats associated with the application of artificial intelligence in connection with sport research, coaching, and optimization of athletic performance: a brief SWOT analysis}, series = {Frontiers in Sports and Active Living}, volume = {5}, journal = {Frontiers in Sports and Active Living}, doi = {10.3389/fspor.2023.1258562}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357973}, year = {2023}, abstract = {Here, we performed a non-systematic analysis of the strength, weaknesses, opportunities, and threats (SWOT) associated with the application of artificial intelligence to sports research, coaching and optimization of athletic performance. The strength of AI with regards to applied sports research, coaching and athletic performance involve the automation of time-consuming tasks, processing and analysis of large amounts of data, and recognition of complex patterns and relationships. However, it is also essential to be aware of the weaknesses associated with the integration of AI into this field. For instance, it is imperative that the data employed to train the AI system be both diverse and complete, in addition to as unbiased as possible with respect to factors such as the gender, level of performance, and experience of an athlete. Other challenges include e.g., limited adaptability to novel situations and the cost and other resources required. Opportunities include the possibility to monitor athletes both long-term and in real-time, the potential discovery of novel indicators of performance, and prediction of risk for future injury. Leveraging these opportunities can transform athletic development and the practice of sports science in general. Threats include over-dependence on technology, less involvement of human expertise, risks with respect to data privacy, breaching of the integrity and manipulation of data, and resistance to adopting such new technology. Understanding and addressing these SWOT factors is essential for maximizing the benefits of AI while mitigating its risks, thereby paving the way for its successful integration into sport science research, coaching, and optimization of athletic performance.}, language = {en} } @article{BuergerSchoenfeldScheineretal.2023, author = {B{\"u}rger, Arne and Schoenfeld, Cornelia von and Scheiner, Christin and Seidel, Alexandra and Wasserscheid, Antonia and Gad, Doreya and Kittel-Schneider, Sarah and Romanos, Marcel and Reiter, Andrea M. F.}, title = {Universal prevention for non-suicidal self-injury in adolescents is scarce - A systematic review}, series = {Frontiers in Psychiatry}, volume = {14}, journal = {Frontiers in Psychiatry}, doi = {10.3389/fpsyt.2023.1130610}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357490}, year = {2023}, abstract = {Non-suicidal self-injury (NSSI) during adolescence is a high-risk marker for the development and persistence of mental health problems and has been recognized as a significant public health problem. Whereas targeted prevention has indeed shown to be effective in reducing NSSI and improve mental health problems, access to such programs is limited. By face validity, universal prevention of NSSI seems an ideal starting point for a stepped-care model to circumvent a lack of resources in the medical care system. However, it is yet unclear how effective such approaches are. Here, we provide a summary of existing work on universal prevention of NSSI in adolescents younger than 21 years based on a systematic literature search. We found that only seven studies are available. None of the programs evaluated was found to be effective in reducing the incidence or frequency of NSSI. After providing a comprehensive summary of the existing work, we evaluate the fact that existing work primarily focusses on selected/targeted prevention and on psychoeducational methods. We derive implications for future directions in the field of universal prevention of NSSI.}, language = {en} } @article{MurtiFenderGlatzleetal.2023, author = {Murti, Krisna and Fender, Hendrik and Glatzle, Carolin and Wismer, Rhoda and Sampere-Birlanga, Salvador and Wild, Vanessa and Muhammad, Khalid and Rosenwald, Andreas and Serfling, Edgar and Avots, Andris}, title = {Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells}, series = {Frontiers in Oncology}, volume = {13}, journal = {Frontiers in Oncology}, doi = {10.3389/fonc.2023.1205788}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323103}, year = {2023}, abstract = {In Burkitt lymphoma (BL), a tumor of germinal center B cells, the pro-apoptotic properties of MYC are controlled by tonic B cell receptor (BCR) signals. Since BL cells do not exhibit constitutive NF-κB activity, we hypothesized that anti-apoptotic NFATc1 proteins provide a major transcriptional survival signal in BL. Here we show that post-transcriptional mechanisms are responsible for the calcineurin (CN) independent constitutive nuclear over-expression of NFATc1 in BL and Eµ-MYC - induced B cell lymphomas (BCL). Conditional inactivation of the Nfatc1 gene in B cells of Eµ-MYC mice leads to apoptosis of BCL cells in vivo and ex vivo. Inhibition of BCR/SYK/BTK/PI3K signals in BL cells results in cytosolic re-location of NFATc1 and apoptosis. Therefore, NFATc1 activity is an integrated part of tonic BCR signaling and an alternative target for therapeutic intervention in BL.}, language = {en} } @article{daSilvaSeiffertTovote2023, author = {da Silva, Gabriela Neubert and Seiffert, Nina and Tovote, Philip}, title = {Cerebellar contribution to the regulation of defensive states}, series = {Frontiers in Systems Neuroscience}, volume = {17}, journal = {Frontiers in Systems Neuroscience}, doi = {10.3389/fnsys.2023.1160083}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311620}, year = {2023}, abstract = {Despite fine tuning voluntary movement as the most prominently studied function of the cerebellum, early human studies suggested cerebellar involvement emotion regulation. Since, the cerebellum has been associated with various mood and anxiety-related conditions. Research in animals provided evidence for cerebellar contributions to fear memory formation and extinction. Fear and anxiety can broadly be referred to as defensive states triggered by threat and characterized by multimodal adaptations such as behavioral and cardiac responses integrated into an intricately orchestrated defense reaction. This is mediated by an evolutionary conserved, highly interconnected network of defense-related structures with functional connections to the cerebellum. Projections from the deep cerebellar nucleus interpositus to the central amygdala interfere with retention of fear memory. Several studies uncovered tight functional connections between cerebellar deep nuclei and pyramis and the midbrain periaqueductal grey. Specifically, the fastigial nucleus sends direct projections to the ventrolateral PAG to mediate fear-evoked innate and learned freezing behavior. The cerebellum also regulates cardiovascular responses such as blood pressure and heart rate-effects dependent on connections with medullary cardiac regulatory structures. Because of the integrated, multimodal nature of defensive states, their adaptive regulation has to be highly dynamic to enable responding to a moving threatening stimulus. In this, predicting threat occurrence are crucial functions of calculating adequate responses. Based on its role in prediction error generation, its connectivity to limbic regions, and previous results on a role in fear learning, this review presents the cerebellum as a regulator of integrated cardio-behavioral defensive states.}, language = {en} } @article{RauschenbergerPiroKasaragodetal.2023, author = {Rauschenberger, Vera and Piro, Inken and Kasaragod, Vikram Babu and H{\"o}rlin, Verena and Eckes, Anna-Lena and Kluck, Christoph J. and Schindelin, Hermann and Meinck, Hans-Michael and Wickel, Jonathan and Geis, Christian and T{\"u}z{\"u}n, Erdem and Doppler, Kathrin and Sommer, Claudia and Villmann, Carmen}, title = {Glycine receptor autoantibody binding to the extracellular domain is independent from receptor glycosylation}, series = {Frontiers in Molecular Neuroscience}, volume = {16}, journal = {Frontiers in Molecular Neuroscience}, doi = {10.3389/fnmol.2023.1089101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304206}, year = {2023}, abstract = {Glycine receptor (GlyR) autoantibodies are associated with stiff-person syndrome and the life-threatening progressive encephalomyelitis with rigidity and myoclonus in children and adults. Patient histories show variability in symptoms and responses to therapeutic treatments. A better understanding of the autoantibody pathology is required to develop improved therapeutic strategies. So far, the underlying molecular pathomechanisms include enhanced receptor internalization and direct receptor blocking altering GlyR function. A common epitope of autoantibodies against the GlyRα1 has been previously defined to residues 1A-33G at the N-terminus of the mature GlyR extracellular domain. However, if other autoantibody binding sites exist or additional GlyR residues are involved in autoantibody binding is yet unknown. The present study investigates the importance of receptor glycosylation for binding of anti-GlyR autoantibodies. The glycine receptor α1 harbors only one glycosylation site at the amino acid residue asparagine 38 localized in close vicinity to the identified common autoantibody epitope. First, non-glycosylated GlyRs were characterized using protein biochemical approaches as well as electrophysiological recordings and molecular modeling. Molecular modeling of non-glycosylated GlyRα1 did not show major structural alterations. Moreover, non-glycosylation of the GlyRα1N38Q did not prevent the receptor from surface expression. At the functional level, the non-glycosylated GlyR demonstrated reduced glycine potency, but patient GlyR autoantibodies still bound to the surface-expressed non-glycosylated receptor protein in living cells. Efficient adsorption of GlyR autoantibodies from patient samples was possible by binding to native glycosylated and non-glycosylated GlyRα1 expressed in living not fixed transfected HEK293 cells. Binding of patient-derived GlyR autoantibodies to the non-glycosylated GlyRα1 offered the possibility to use purified non-glycosylated GlyR extracellular domain constructs coated on ELISA plates and use them as a fast screening readout for the presence of GlyR autoantibodies in patient serum samples. Following successful adsorption of patient autoantibodies by GlyR ECDs, binding to primary motoneurons and transfected cells was absent. Our results indicate that the glycine receptor autoantibody binding is independent of the receptor's glycosylation state. Purified non-glycosylated receptor domains harbouring the autoantibody epitope thus provide, an additional reliable experimental tool besides binding to native receptors in cell-based assays for detection of autoantibody presence in patient sera.}, language = {en} } @article{KirchnerSchrammIvanovaetal.2024, author = {Kirchner, Philipp H. and Schramm, Louis and Ivanova, Svetlana and Shoyama, Kazutaka and W{\"u}rthner, Frank and Beuerle, Florian}, title = {A water-stable boronate ester cage}, series = {Journal of the American Chemical Society}, volume = {146}, journal = {Journal of the American Chemical Society}, number = {8}, issn = {0002-7863}, doi = {10.1021/jacs.3c12002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361245}, pages = {5305-5315}, year = {2024}, abstract = {The reversible condensation of catechols and boronic acids to boronate esters is a paradigm reaction in dynamic covalent chemistry. However, facile backward hydrolysis is detrimental for stability and has so far prevented applications for boronate-based materials. Here, we introduce cubic boronate ester cages 6 derived from hexahydroxy tribenzotriquinacenes and phenylene diboronic acids with ortho-t-butyl substituents. Due to steric shielding, dynamic exchange at the Lewis acidic boron sites is feasible only under acid or base catalysis but fully prevented at neutral conditions. For the first time, boronate ester cages 6 tolerate substantial amounts of water or alcohols both in solution and solid state. The unprecedented applicability of these materials under ambient and aqueous conditions is showcased by efficient encapsulation and on-demand release of β-carotene dyes and heterogeneous water oxidation catalysis after the encapsulation of ruthenium catalysts.}, language = {en} } @article{NollWuerthner2024, author = {Noll, Niklas and W{\"u}rthner, Frank}, title = {Bioinspired water preorganization in confined space for efficient water oxidation catalysis in metallosupramolecular ruthenium architectures}, series = {Accounts of Chemical Research}, volume = {57}, journal = {Accounts of Chemical Research}, number = {10}, issn = {0001-4842}, doi = {10.1021/acs.accounts.4c00148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-361232}, pages = {1538-1549}, year = {2024}, abstract = {Conspectus Nature has established a sustainable way to maintain aerobic life on earth by inventing one of the most sophisticated biological processes, namely, natural photosynthesis, which delivers us with organic matter and molecular oxygen derived from the two abundant resources sunlight and water. The thermodynamically demanding photosynthetic water splitting is catalyzed by the oxygen-evolving complex in photosystem II (OEC-PSII), which comprises a distorted tetramanganese-calcium cluster (CaMn\(_4\)O\(_5\)) as catalytic core. As an ubiquitous concept for fine-tuning and regulating the reactivity of the active site of metalloenzymes, the surrounding protein domain creates a sophisticated environment that promotes substrate preorganization through secondary, noncovalent interactions such as hydrogen bonding or electrostatic interactions. Based on the high-resolution X-ray structure of PSII, several water channels were identified near the active site, which are filled with extensive hydrogen-bonding networks of preorganized water molecules, connecting the OEC with the protein surface. As an integral part of the outer coordination sphere of natural metalloenzymes, these channels control the substrate and product delivery, carefully regulate the proton flow by promoting pivotal proton-coupled electron transfer processes, and simultaneously stabilize short-lived oxidized intermediates, thus highlighting the importance of an ordered water network for the remarkable efficiency of the natural OEC. Transferring this concept from nature to the engineering of artificial metal catalysts for fuel production has fostered the fascinating field of metallosupramolecular chemistry by generating defined cavities that conceptually mimic enzymatic pockets. However, the application of supramolecular approaches to generate artificial water oxidation catalysts remained scarce prior to our initial reports, since such molecular design strategies for efficient activation of substrate water molecules in confined nanoenvironments were lacking. In this Account, we describe our research efforts on combining the state-of-the art Ru(bda) catalytic framework with structurally programmed ditopic ligands to guide the water oxidation process in defined metallosupramolecular assemblies in spatial proximity. We will elucidate the governing factors that control the quality of hydrogen-bonding water networks in multinuclear cavities of varying sizes and geometries to obtain high-performance, state-of-the-art water oxidation catalysts. Pushing the boundaries of artificial catalyst design, embedding a single catalytic Ru center into a well-defined molecular pocket enabled sophisticated water preorganization in front of the active site through an encoded basic recognition site, resulting in high catalytic rates comparable to those of the natural counterpart OEC-PSII. To fully explore their potential for solar fuel devices, the suitability of our metallosupramolecular assemblies was demonstrated under (electro)chemical and photocatalytic water oxidation conditions. In addition, testing the limits of structural diversity allowed the fabrication of self-assembled linear coordination oligomers as novel photocatalytic materials and long-range ordered covalent organic framework (COF) materials as recyclable and long-term stable solid-state materials for future applications.}, language = {en} } @article{KleihDahmsBotrel2023, author = {Kleih-Dahms, Sonja C. and Botrel, Loic}, title = {Neurofeedback therapy to improve cognitive function in patients with chronic post-stroke attention deficits: a within-subjects comparison}, series = {Frontiers in Human Neuroscience}, volume = {17}, journal = {Frontiers in Human Neuroscience}, doi = {10.3389/fnhum.2023.1155584}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322454}, year = {2023}, abstract = {Introduction We investigated a slow-cortical potential (SCP) neurofeedback therapy approach for rehabilitating chronic attention deficits after stroke. This study is the first attempt to train patients who survived stroke with SCP neurofeedback therapy. Methods We included N = 5 participants in a within-subjects follow-up design. We assessed neuropsychological and psychological performance at baseline (4 weeks before study onset), before study onset, after neurofeedback training, and at 3 months follow-up. Participants underwent 20 sessions of SCP neurofeedback training. Results Participants learned to regulate SCPs toward negativity, and we found indications for improved attention after the SCP neurofeedback therapy in some participants. Quality of life improved throughout the study according to engagement in activities of daily living. The self-reported motivation was related to mean SCP activation in two participants. Discussion We would like to bring attention to the potential of SCP neurofeedback therapy as a new rehabilitation method for treating post-stroke cognitive deficits. Studies with larger samples are warranted to corroborate the results.}, language = {en} } @article{GoepfertTraubSelletal.2023, author = {G{\"o}pfert, Dennis and Traub, Jan and Sell, Roxane and Homola, Gy{\"o}rgy A. and Vogt, Marius and Pham, Mirko and Frantz, Stefan and St{\"o}rk, Stefan and Stoll, Guido and Frey, Anna}, title = {Profiles of cognitive impairment in chronic heart failure—A cluster analytic approach}, series = {Frontiers in Human Neuroscience}, volume = {17}, journal = {Frontiers in Human Neuroscience}, doi = {10.3389/fnhum.2023.1126553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313429}, year = {2023}, abstract = {Background Cognitive impairment is a major comorbidity in patients with chronic heart failure (HF) with a wide range of phenotypes. In this study, we aimed to identify and compare different clusters of cognitive deficits. Methods The prospective cohort study "Cognition.Matters-HF" recruited 147 chronic HF patients (aged 64.5 ± 10.8 years; 16.2\% female) of any etiology. All patients underwent extensive neuropsychological testing. We performed a hierarchical cluster analysis of the cognitive domains, such as intensity of attention, visual/verbal memory, and executive function. Generated clusters were compared exploratively with respect to the results of cardiological, neurological, and neuroradiological examinations without correction for multiple testing. Results Dendrogram and the scree plot suggested three distinct cognitive profiles: In the first cluster, 42 patients (28.6\%) performed without any deficits in all domains. Exclusively, the intensity of attention deficits was seen in the second cluster, including 55 patients (37.4\%). A third cluster with 50 patients (34.0\%) was characterized by deficits in all cognitive domains. Age (p = 0.163) and typical clinical markers of chronic HF, such as ejection fraction (p = 0.222), 6-min walking test distance (p = 0.138), NT-proBNP (p = 0.364), and New York Heart Association class (p = 0.868) did not differ between clusters. However, we observed that women (p = 0.012) and patients with previous cardiac valve surgery (p = 0.005) prevailed in the "global deficits" cluster and the "no deficits" group had a lower prevalence of underlying arterial hypertension (p = 0.029). Total brain volume (p = 0.017) was smaller in the global deficit cluster, and serum levels of glial fibrillary acidic protein were increased (p = 0.048). Conclusion Apart from cognitively healthy and globally impaired HF patients, we identified a group with deficits only in the intensity of attention. Women and patients with previous cardiac valve surgery are at risk for global cognitive impairment when suffering HF and could benefit from special multimodal treatment addressing the psychosocial condition.}, language = {en} } @article{LehriederZapantisPhametal.2023, author = {Lehrieder, Dominik and Zapantis, Nikolaos and Pham, Mirko and Schuhmann, Michael Klaus and Haarmann, Axel}, title = {Treating seronegative neuromyelitis optica spectrum disorder with inebilizumab: a case report}, series = {Frontiers in Neurology}, volume = {14}, journal = {Frontiers in Neurology}, doi = {10.3389/fneur.2023.1297341}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-354031}, year = {2023}, abstract = {Background Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory disease of the central nervous system that is often severely disabling from the outset. The lack of pathognomonic aquaporin 4 (AQP4) antibodies in seronegative NMOSD not only hinders early diagnosis, but also limits therapeutic options, in contrast to AQP4 antibody-positive NMOSD, where the therapeutic landscape has recently evolved massively. Case presentation We report a 56-year-old woman with bilateral optic neuritis and longitudinally extensive myelitis as the index events of a seronegative NMOSD, who was successfully treated with inebilizumab. Conclusion Treatment with inebilizumab may be considered in aggressive seronegative NMOSD. Whether broader CD19-directed B cell depletion is more effective than treatment with rituximab remains elusive.}, language = {en} } @article{RebsStreckfussBoemeke2023, author = {Rebs, Sabine and Streckfuss-B{\"o}meke, Katrin}, title = {How can we use stem cell-derived cardiomyocytes to understand the involvement of energetic metabolism in alterations of cardiac function?}, series = {Frontiers in Molecular Medicine}, volume = {3}, journal = {Frontiers in Molecular Medicine}, doi = {10.3389/fmmed.2023.1222986}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327344}, year = {2023}, abstract = {Mutations in the mitochondrial-DNA or mitochondria related nuclear-encoded-DNA lead to various multisystemic disorders collectively termed mitochondrial diseases. One in three cases of mitochondrial disease affects the heart muscle, which is called mitochondrial cardiomyopathy (MCM) and is associated with hypertrophic, dilated, and noncompact cardiomyopathy. The heart is an organ with high energy demand, and mitochondria occupy 30\%-40\% of its cardiomyocyte-cell volume. Mitochondrial dysfunction leads to energy depletion and has detrimental effects on cardiac performance. However, disease development and progression in the context of mitochondrial and nuclear DNA mutations, remains incompletely understood. The system of induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) is an excellent platform to study MCM since the unique genetic identity to their donors enables a robust recapitulation of the predicted phenotypes in a dish on a patient-specific level. Here, we focus on recent insights into MCM studied by patient-specific iPSC-CM and further discuss research gaps and advances in metabolic maturation of iPSC-CM, which is crucial for the study of mitochondrial dysfunction and to develop novel therapeutic strategies.}, language = {en} } @article{FroehlichZahnerSchmalzingetal.2023, author = {Froehlich, Matthias and Zahner, Antonia and Schmalzing, Marc and Gernert, Michael and Strunz, Patrick-Pascal and Hueper, Sebastian and Portegys, Jan and Schwaneck, Eva Christina and Gadeholt, Ottar and K{\"u}bler, Andrea and Hewig, Johannes and Ziebell, Philipp}, title = {Patient-reported outcomes provide evidence for increased depressive symptoms and increased mental impairment in giant cell arteritis}, series = {Frontiers in Medicine}, volume = {10}, journal = {Frontiers in Medicine}, doi = {10.3389/fmed.2023.1146815}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319761}, year = {2023}, abstract = {Objectives The spectrum of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) represents highly inflammatory rheumatic diseases. Patients mostly report severe physical impairment. Possible consequences for mental health have been scarcely studied. The aim of this study was to investigate psychological well-being in the context of GCA and PMR. Methods Cross-sectional study with N = 100 patients with GCA and/or PMR (GCA-PMR). Patient-reported outcomes (PROs) were measured using the Short Form 36 Version 2 (SF-36v2) and visual analog scale (VAS) assessment. Moreover, the Patient Health Questionnaire 9 (PHQ-9) was used in 35 of 100 patients to detect depression. To compare PROs with physician assessment, VAS was also rated from physician perspective. To assess a possible association with inflammation itself, serological parameters of inflammation (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) were included. Results In all scales of the SF-36v2 except General Health (GH) and in the physical and mental sum score (PCS, MCS), a significant impairment compared to the German reference collective was evident (MCS: d = 0.533, p < 0.001). In the PHQ-9 categorization, 14 of the 35 (40\%) showed evidence of major depression disorder. VAS Patient correlated significantly with PHQ-9 and SF-36 in all categories, while VAS Physician showed only correlations to physical categories and not in the mental dimensions. Regarding inflammatory parameters, linear regression showed CRP to be a complementary significant positive predictor of mental health subscale score, independent of pain. Conclusion PRO show a relevant impairment of mental health up to symptoms of major depression disorder. The degree of depressive symptoms is also distinctly associated with the serological inflammatory marker CRP.}, language = {en} }