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Babiano Suarez, Victor ; Lerendegui-Marco, Jorge ; Balibrea Correa, Javier ; Caballero Ontanaya, Luis ; Calvo, David ; Ladarescu, Ion ; Domingo-Pardo, César ; Calviño Tavares, Francisco ; Casanovas Hoste, Adrià ; Tarifeño-Saldivia, Ariel ; Alcayne, Victor ; Guerrero Sánchez, Carlos ; Millán Callado, María de los Ángeles ; Rodrı́guez-González, María Teresa ; Barbagallo, Massimo ; Aberle, Oliver ; Amaducci, Simone ; Andrzejewski, Józef ; Audouin, Laurent ; Bacak, Michael ; Bennett, Samuel ; Berthoumieux, Eric ; Billowes, Jonathan ; Bosnar, Damir ; Brown, Adam ; Busso, Maurizio ; Caamaño, Manuel ; Calviani, Marco ; Cano-Ott, Daniel ; Cerutti, Francesco ; Chiaveri, Enrico ; Colonna, Nicola ; Cortés Rossell, Guillem Pere ; Cortés-Giraldo, Miguel Antonio ; Cosentino, Luigi ; Cristallo, Sergio ; Damone, Lucia Anna ; Davies, Paul John ; Diakaki, Maria ; Dietz, Mirco ; Dressler, Rugard ; Ducasse, Quentin ; Dupont, Emmeric ; Durán, Ignacio ; Eleme, Zinovia ; Fernández Domínguez, Beatriz ; Ferrari, Alfredo ; Finocchiaro, Paolo ; Furman, Valter ; Göbel, Kathrin ; Garg, Ruchi ; Gawlik, Aleksandra ; Gilardoni, Simone ; Gonçalves, Isabel Maria Ferro ; González Romero, Enrique Miguel ; Gunsing, Frank ; Harada, Hideo ; Heinitz, Stephan ; Heyse, Jan ; Jenkins, David ; Junghans, Arnd Rudolf ; Käppeler, Franz ; Kadi, Yacine ; Kimura, Atsushi ; Knapova, Ingrid ; Kokkoris, Michael ; Kopatch, Yuri N. ; Krtička, Milan ; Kurtulgil, Cem Deniz ; Lederer-Woods, Claudia ; Leeb, Helmut ; Lonsdale, Sarah Jane ; Macina, Daniela ; Manna, Alice ; Martinez, Trinitario ; Masi, Alessandro ; Massimi, Cristian ; Mastinu, Pierfrancesco ; Mastromarco, Mario ; Maugeri, Emilio Andrea ; Mazzone, Annamaria ; Mendoza Cembranos, Emilio ; Mengoni, Alberto ; Michalopoulou, Veatriki ; Milazzo, Paolo Maria ; Mingrone, Federica ; Moreno-Soto, Javier ; Musumarra, Agatino ; Negret, Alexandru ; Ogállar Ruiz, Francisco ; Oprea, Andreea ; Patronis, Nikolas ; Pavlik, Andreas ; Perkowski, Jarosław ; Piersanti, Luciano ; Petrone, Cristina ; Pirovano, Elisa ; Porras Sánchez, José Ignacio ; Praena, Javier ; Quesada Molina, José Manuel ; Ramos Doval, Diego ; Rauscher, Thomas ; Reifarth, René ; Rochman, Dimitri ; Rubbia, Carlo ; Sabaté-Gilarte, Marta ; Saxena, Alok ; Schillebeeckx, Peter ; Schumann, Dorothea ; Sekhar, Adhitya ; Smith, Alastair Gavin ; Sosnin, Nikolay V. ; Sprung, Peter ; Stamatopoulos, Athanasios ; Tagliente, Giuseppe ; Taı́n Enríquez, José Luis ; Tassan-Got, Laurent ; Thomas, Th. ; Torres-Sánchez, Pablo ; Tsinganis, Andrea ; Ulrich, Jiri ; Urlaß, Sebastian ; Valenta, Stanislav ; Vannini, Gianni ; Variale, Vincenzo ; Vaz, Pedro ; Ventura, Alberto ; Vescovi, Diego ; Vlachoudis, Vasilis ; Vlastou, Rosa ; Wallner, Anton ; Woods, Philip John ; Wright, Tobias ; Žugec, Petar
i-TED is an innovative detection system which exploits Compton imaging techniques to achieve a superior signal-to-background ratio in (n,γ) cross-section measurements using time-of-flight technique. This work presents the first experimental validation of the i-TED apparatus for high-resolution time-of-flight experiments and demonstrates for the first time the concept proposed for background rejection. To this aim both 197Au(n,γ) and 56Fe(n,γ) reactions were measured at CERN n\_TOF using an i-TED demonstrator based on only three position-sensitive detectors. Two \cds detectors were also used to benchmark the performance of i-TED. The i-TED prototype built for this study shows a factor of ∼3 higher detection sensitivity than state-of-the-art \cds detectors in the ∼10~keV neutron energy range of astrophysical interest. This paper explores also the perspectives of further enhancement in performance attainable with the final i-TED array consisting of twenty position-sensitive detectors and new analysis methodologies based on Machine-Learning techniques.
Borsch, Thomas ; Stevens, Albert-Dieter ; Häffner, Eva ; Güntsch, Anton ; Berendsohn, Walter G. ; Appelhans, Marc Sebastian ; Barilaro, Christina ; Beszteri, Bánk ; Blattner, Frank R. ; Bossdorf, Oliver ; Dalitz, Helmut ; Dressler, Stefan ; Duque-Thüs, Rhinaixa ; Esser, Hans-Joachim ; Franzke, Andreas ; Goetze, Dethardt ; Grein, Michaela ; Grünert, Uta ; Hellwig, Frank ; Hentschel, Jörn ; Hörandl, Elvira ; Janßen, Thomas ; Jürgens, Norbert ; Kadereit, Gudrun ; Karisch, Timm ; Koch, Marcus ; Müller, Frank ; Müller, Jochen ; Ober, Dietrich ; Porembski, Stefan ; Poschlod, Peter ; Printzen, Christian ; Röser, Martin ; Sack, Peter ; Schlüter, Philipp M. ; Schmidt, Marco ; Schnittler, Martin ; Scholler, Markus ; Schultz, Matthias ; Seeber, Elke ; Simmel, Josef ; Stiller, Michael ; Thiv, Mike ; Thüs, Holger ; Tkach, Natalia ; Triebel, Dagmar ; Warnke, Ursula ; Weibulat, Tanja ; Wesche, Karsten ; Yurkov, Andrey ; Zizka, Georg
Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool.
Marwitz, Sebastian ; Turkowski, Kati ; Nitschkowski, Dörte ; Weigert, Andreas ; Brandenburg, Julius ; Reiling, Norbert ; Thomas, Michael ; Reck, Martin ; Drömann, Daniel ; Seeger, Werner ; Rabe, Klaus F. ; Savai, Rajkumar ; Goldmann, Torsten
Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition via Pirfenidone by using flow cytometry, In-Cell western analysis, proliferation assays as well as comprehensive analyses of the transcriptome with subsequent bioinformatics analysis. Overall, Pirfenidone induced cell cycle arrest, down-regulated SMAD expression and reduced proliferation in lung cancer. Furthermore, cell stress pathways and pro-apoptotic signaling may be mediated by reduced expression of Survivin. A murine subcutaneous model was used to assess the in vivo drug efficacy of Pirfenidone and showed reduced tumor growth and increased infiltration of T cells and NK cells. This data warrant further clinical evaluation of Pirfenidone with advanced non-small cell lung cancer. The observed in vitro and in vivo effects point to a substantial benefit for using Pirfenidone to reactivate the local immune response and possible application in conjunction with current immunotherapies.
Warris, Adilia ; Pana, Zoi-Dorothea ; Oletto, Andrea ; Lundin, Rebecca ; Castagnola, Elio ; Lehrnbecher, Thomas ; Groll, Andreas Hermann ; Roilides, Emmanuel
Background: Data on Candida bloodstream infections in pediatric patients in Europe are limited. We performed a retrospective multicenter European study of the epidemiology and outcome of neonatal and pediatric candidemia.
Material and Methods: All first positive blood cultures from patients ≤ 18 years of age with candidemia were registered. Patients’ demographic and clinical characteristics and causative Candida species were collected and analyzed. Regression analysis was used to identify factors independently associated with mortality.
Results: One thousand three hundred ninety-five episodes of candidemia (57.8% male) were reported from 23 hospitals in 10 European countries. Of the 1395 episodes, 36.4% occurred in neonates (≤ 44 weeks postmenstrual age), 13.8% in infants (> 44 weeks postmenstrual age to 1 year) and 49.8% in children and adolescents. Candida albicans (52.5%) and Candida parapsilosis (28%) were the predominant species. A higher proportion of candidemia caused by C. albicans was observed among neonatal patients (60.2%) with highest rates of C. parapsilosis seen among infants (42%). Children admitted to hematology-oncology wards presented the highest rates of non-albicans Candida species. Candidemia because of C. albicans was more frequent than non-albicans Candida in Northern versus Southern Europe (odds ratio, 2.3; 95% confidence interval, 1.8–2.9; P < 0.001). The all-cause mortality at 30 days was 14.4%. All-cause mortality was higher among patients admitted to the neonatal or pediatric intensive care units than other wards. Over time, no significant changes in species distribution were observed.
Conclusions: This first multicenter European study shows unique characteristics of the epidemiology of pediatric candidemia. The insights obtained from this study will be useful to guide clinical management and antifungal stewardship.
Junghans, Arnd Rudolf ; Beyer, Roland ; Claußner, Jürgen ; Kögler, Toni ; Urlaß, Sebastian ; Bemmerer, Daniel ; Ferrari, Anna ; Schwengner, Ronald ; Wagner, Andreas ; Dietz, Mirco ; Frotscher, Axel ; Grieger, Marcel ; Hensel, Thomas ; Koppitz, Martina ; Ludwig, Felix ; Turkat, Steffen ; Nolte, Ralf ; Pirovano, Elisa ; Kopecky, Stefan ; Nyman, Markus ; Plompen, Arjan J. M. ; Schillebeeckx, Peter ; Borris, Erik ; Reifarth, René ; Veltum, Daniel ; Weigand, Mario ; Glorius, Jan ; Görres, Joachim ; Oberlack, Uwe ; Wenz, Daniel
Neutron total cross sections are an important source of experimental data in the evaluation of neutron-induced cross sections. The sum of all neutron-induced reaction cross sections can be determined with a precision of a few per cent in a relative measurement. The neutron spectrum of the photoneutron source nELBE extends in the fast region from about 100 keV to 10 MeV and has favourable conditions for transmission measurements due to the low instantaneous flux of neutrons and low gamma-flash background. Several materials of interest (in part included in the CIELO evaluation or on the HPRL of OECD/NEA) have been investigated: 197Au [1, 2], natFe [2], natW [2], 238U, natPt, 4He, natO, natNe, natXe. For gaseous targets high pressure gas cells with flat end-caps have been built that hold up to 200 bar pressure. The experimental setup will be presented including results from several transmission experiments and the data analysis leading to the total cross sections will be discussed.
Trösemeier, Jan-Hendrik ; Rudorf, Sophia ; Lößner, Holger ; Hofner, Benjamin ; Reuter, Andreas ; Schulenborg, Thomas ; Koch, Ina ; Bekeredjian-Ding, Isabelle ; Lipowsky, Reinhard ; Kamp, Christel
Correction to: Scientifc Reports https://doi.org/10.1038/s41598-019-43857-5, published online 17 May 2019. In the original version of this Article, Jan-Hendrik Trösemeier was incorrectly affiliated with ‘Division of Allergology, Paul Ehrlich Institut, Langen, Germany’. Te correct afliations are listed below...
Le, Melanie T. P. ; Zarinabad, Niloufar ; D’Angelo, Tommaso ; Mia, Ibnul ; Heinke, Robert ; Vogl, Thomas J. ; Zeiher, Andreas M. ; Nagel, Eike ; Puntmann, Valentina O.
Background: Myocardial perfusion with cardiovascular magnetic resonance (CMR) imaging is an established diagnostic test for evaluation of myocardial ischaemia. For quantification purposes, the 16 segment American Heart Association (AHA) model poses limitations in terms of extracting relevant information on the extent/severity of ischaemia as perfusion deficits will not always fall within an individual segment, which reduces its diagnostic value, and makes an accurate assessment of outcome data or a result comparison across various studies difficult. We hypothesised that division of the myocardial segments into epi- and endocardial layers and a further circumferential subdivision, resulting in a total of 96 segments, would improve the accuracy of detecting myocardial hypoperfusion. Higher (sub-)subsegmental recording of perfusion abnormalities, which are defined relatively to the normal reference using the subsegment with the highest value, may improve the spatial encoding of myocardial blood flow, based on a single stress perfusion acquisition. Objective: A proof of concept comparison study of subsegmentation approaches based on transmural segments (16 AHA and 48 segments) vs. subdivision into epi- and endocardial (32) subsegments vs. further circumferential subdivision into 96 (sub-)subsegments for diagnostic accuracy against invasively defined obstructive coronary artery disease (CAD). Methods: Thirty patients with obstructive CAD and 20 healthy controls underwent perfusion stress CMR imaging at 3 T during maximal adenosine vasodilation and a dual bolus injection of 0.1mmol/kg gadobutrol. Using Fermi deconvolution for blood flow estimation, (sub-)subsegmental values were expressed relative to the (sub)subsegment with the highest flow. In addition, endo−/epicardial flow ratios were calculated based on 32 and 96 (sub-)subsegments. A receiver operating characteristics (ROC) curve analysis was performed to compare the diagnostic performance of discrimination between patients with CAD and healthy controls. Observer reproducibility was assessed using Bland-Altman approaches. Results: Subdivision into more and smaller segments revealed greater accuracy for #32, #48 and # 96 compared to the standard #16 approach (area under the curve (AUC): 0.937, 0.973 and 0.993 vs 0.820, p<0.05). The #96-based endo−/epicardial ratio was superior to the #32 endo−/epicardial ratio (AUC 0.979, vs. 0.932, p<0.05). Measurements for the #16 model showed marginally better reproducibility compared to #32, #48 and #96 (mean difference± standard deviation: 2.0±3.6 vs. 2.3±4.0 vs 2.5±4.4 vs. 4.1±5.6). Conclusions: Subsegmentation of the myocardium improves diagnostic accuracy and facilitates an objective cutoff-based description of hypoperfusion, and facilitates an objective description of hypoperfusion, including the extent and severity of myocardial ischaemia. Quantification based on a single (stress-only) pass reduces the overall amount of gadolinium contrast agent required and the length of the overall diagnostic study.
Blessing, Recha ; Ahoopai, Majid ; Geyer, Martin ; Brandt, Moritz ; Zeiher, Andreas M. ; Münzel, Thomas ; Wenzel, Philip ; Gori, Tommaso ; Dimitriadis, Zisis
We sought to determine the effects of the use of a Bioengineered Combo Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Coronary Stent (Combo® DTS) in patients with chronic total occlusion (CTO) by evaluating clinical outcomes and by performing an optical coherence tomography (OCT) analysis. We retrospectively analyzed data from 39 patients who had successfully undergone OCT-guided revascularization of a CTO being treated with a Combo® DTS. Clinical assessment, angiography (with quantitative coronary angiography analysis) and OCT examination were performed at baseline and at follow-up. The median follow-up period was 189 days, ranging from 157 to 615 days. At follow-up, revascularization was required due to angiographic restenosis in 40% (14 of 35) of patients. OCT analysis detected neointima proliferation in 23 (76.6%) patients. Neointima formation was often associated with microvessels in 18 patients (60%). Neoatheroslcerosis was observed in 2 (6.6%) patients. Malapposition was found in 4 patients (13.3%), and stent fractures were found in 11 patients (36.6%). Rate of strut coverage was 96.3% at follow-up. In conclusion, the implantation of a Combo® DTS after successful CTO recanalization was associated with a restenosis rate of 40% despite good stent implantation at baseline, proven by OCT. Neointima formation was found as a main contributor to restenosis. Nevertheless, we observed a low rate of major cardiovascular events in our follow-up.
Bernatz, Simon ; Ackermann, Jörg ; Mandel, Philipp ; Kaltenbach, Benjamin ; Zhdanovich, Yauheniya ; Harter, Patrick Nikolaus ; Döring, Claudia ; Hammerstingl, Renate Maria ; Bodelle, Boris ; Smith, Kevin ; Bucher, Andreas ; Albrecht, Moritz Hans Ernst ; Rosbach, Nicolas ; Basten, Lajos Maximilian ; Yel, Ibrahim ; Wenzel, Mike ; Bankov, Katrin ; Koch, Ina ; Chun, Felix ; Köllermann, Jens ; Wild, Peter Johannes ; Vogl, Thomas J.
Objectives: To analyze the performance of radiological assessment categories and quantitative computational analysis of apparent diffusion coefficient (ADC) maps using variant machine learning algorithms to differentiate clinically significant versus insignificant prostate cancer (PCa). Methods: Retrospectively, 73 patients were included in the study. The patients (mean age, 66.3 ± 7.6 years) were examined with multiparametric MRI (mpMRI) prior to radical prostatectomy (n = 33) or targeted biopsy (n = 40). The index lesion was annotated in MRI ADC and the equivalent histologic slides according to the highest Gleason Grade Group (GrG). Volumes of interest (VOIs) were determined for each lesion and normal-appearing peripheral zone. VOIs were processed by radiomic analysis. For the classification of lesions according to their clinical significance (GrG ≥ 3), principal component (PC) analysis, univariate analysis (UA) with consecutive support vector machines, neural networks, and random forest analysis were performed. Results: PC analysis discriminated between benign and malignant prostate tissue. PC evaluation yielded no stratification of PCa lesions according to their clinical significance, but UA revealed differences in clinical assessment categories and radiomic features. We trained three classification models with fifteen feature subsets. We identified a subset of shape features which improved the diagnostic accuracy of the clinical assessment categories (maximum increase in diagnostic accuracy ΔAUC = + 0.05, p < 0.001) while also identifying combinations of features and models which reduced overall accuracy. Conclusions: The impact of radiomic features to differentiate PCa lesions according to their clinical significance remains controversial. It depends on feature selection and the employed machine learning algorithms. It can result in improvement or reduction of diagnostic performance.
1. Recent research highlights the ecological importance of individual variation in behavioural predictability. Individuals may not only differ in their average expression of a behavioural trait (their behavioural type) and in their ability to adjust behaviour to changing environmental conditions (individual plasticity), but also in their variability around their average behaviour (predictability). However, quantifying behavioural predictability in the wild has been challenging due to limitations of acquiring sufficient repeated behavioural measures.
2. We here demonstrate how common biologging data can be used to detect individual variation in behavioural predictability in the wild and reveal the coexistence of highly predictable individuals along with unpredictable individuals within the same population.
3. We repeatedly quantified two behaviours—daily movement distance and diurnal activity—in 62 female brown bears Ursus arctos tracked across 187 monitoring years. We calculated behavioural predictability over the short term (50 consecutive monitoring days within 1 year) and long term (across monitoring years) as the residual intra-individual variability (rIIV) of behaviour around the behavioural reaction norm. We tested whether predictability varies systematically across average behavioural types and whether it is correlated across functionally distinct behaviours, that is, daily movement distance and amount of diurnal activity.
4. Brown bears showed individual variation in behavioural predictability from predictable to unpredictable individuals. For example, the standard deviation around the average daily movement distance within one monitoring year varied up to fivefold from 1.1 to 5.5 km across individuals. Individual predictability for both daily movement distance and diurnality was conserved across monitoring years. Individual predictability was correlated with behavioural type where individuals which were on average more diurnal and mobile were also more unpredictable in their behaviour. In contrast, more nocturnal individuals moved less and were more predictable in their behaviour. Finally, individual predictability in daily movement distance and diurnality was positively correlated, suggesting that individual predictability may be a quantitative trait in its own regard that could evolve and is underpinned by genetic variation.
5. Unpredictable individuals may cope better with stochastic events and unpredictability may hence be an adaptive behavioural response to increased predation risk.
Seppelt, Philipp ; Mas-Peiro, Silvia ; De Rosa, Roberta ; Murray, Isabell M. ; Arsalan, Mani ; Holzer, Lars ; Lotz, Gösta ; Meybohm, Patrick ; Zacharowski, Kai ; Walther, Thomas ; Zeiher, Andreas M. ; Fichtlscherer, Stephan ; Vasa-Nicotera, Mariuca
Background: Cerebral O2 saturation (ScO2) reflects cerebral perfusion and can be measured noninvasively by near-infrared spectroscopy (NIRS). Objectives: In this pilot study, we describe the dynamics of ScO2 during TAVI in nonventilated patients and its impact on procedural outcome. Methods and Results: We measured ScO2 of both frontal lobes continuously by NIRS in 50 consecutive analgo-sedated patients undergoing transfemoral TAVI (female 58%, mean age 80.8 years). Compared to baseline ScO2 dropped significantly during RVP (59.3% vs. 53.9%, p < .01). Five minutes after RVP ScO2 values normalized (post RVP 62.6% vs. 53.9% during RVP, p < .01; pre 61.6% vs. post RVP 62.6%, p = .53). Patients with an intraprocedural pathological ScO2 decline of >20% (n = 13) had higher EuroSCORE II (3.42% vs. 5.7%, p = .020) and experienced more often delirium (24% vs. 62%, p = .015) and stroke (0% vs. 23%, p < .01) after TAVI. Multivariable logistic regression revealed higher age and large ScO2 drops as independent risk factors for delirium. Conclusions: During RVP ScO2 significantly declined compared to baseline. A ScO2 decline of >20% is associated with a higher incidence of delirium and stroke and a valid cut-off value to screen for these complications. NIRS measurement during TAVI procedure may be an easy to implement diagnostic tool to detect patients at high risks for cerebrovascular complications and delirium.
Bauer, Jochen ; Hechtel, Michael ; Konrad, Christoph ; Holzwarth, Martin ; Mayr, Andreas ; Schneider, Sven ; Franke, Jörg ; Hoffmann, Hilko ; Zinnikus, Ingo ; Feld, Thomas ; Runge, Mathias ; Hinz, Oliver
In the upcoming years, the internet of things (IoT)will enrich daily life. The combination of artificial intelligence(AI) and highly interoperable systems will bring context-sensitive multi-domain services to reality. This paper describesa concept for an AI-based smart living platform with open-HAB, a smart home middleware, and Web of Things (WoT) askey components of our approach. The platform concept con-siders different stakeholders, i.e. the housing industry, serviceproviders, and tenants. These activities are part of the Fore-Sight project, an AI-driven, context-sensitive smart living plat-form.
Wenzel, Mike ; Humke, Clara Julia ; Wicker, Sabine ; Mani, Jens ; Engl, Tobias A. ; Hintereder, Gudrun ; Vogl, Thomas J. ; Wild, Peter Johannes ; Köllermann, Jens ; Rödel, Claus ; Asgharie, S. ; Theißen, Lena Hermine ; Welte, Maria-Noemi ; Kluth, Luis ; Mandel, Philipp ; Chun, Felix ; Preißer, Felix Martin ; Becker, Andreas
hintergrund: Männer in Deutschland sterben früher als Frauen und nehmen weniger häufig Krebsvorsorgeuntersuchungen wahr.
Fragestellung: Ziel war die prospektive Evaluation einer „Movember-Gesundheitsinitiative“ am Universitätsklinikum Frankfurt (UKF) im November 2019.
Methoden: Im Rahmen der „Movember-Gesundheitsinitiative“ wurde allen männlichen Mitarbeitern des UKF ab dem 45. Lebensjahr und bei erstgradiger familiärer Vorbelastung eines Prostatakarzinoms ab dem 40. Lebensjahr im November 2019 gemäß S3-Leitlinien der Deutschen Gesellschaft für Urologie (DGU) eine Prostatakarzinom-Vorsorgeuntersuchung angeboten.
Ergebnisse: Insgesamt nahmen 14,4 % der Mitarbeiter teil. Eine familiäre Vorbelastung gaben insgesamt 14,0 % Teilnehmer an. Das mediane Alter betrug 54 Jahre. Der mediane PSA(prostataspezifisches Antigen)-Wert lag bei 0,9 ng/ml, der mediane PSA-Quotient bei 30 %. Bei 5 % (n = 6) zeigte sich ein suspekter Tastbefund in der DRU (digital-rektale Untersuchung). Nach Altersstratifizierung (≤ 50 vs. > 50 Lebensjahre) zeigten sich signifikante Unterschiede im medianen PSA-Wert (0,7 ng/ml vs. 1,0 ng/ml, p < 0,01) und der bereits zuvor durchgeführten urologischen Vorsorge (12,1 vs. 42,0 %, p < 0,01). Vier Teilnehmer (3,3 %) zeigten erhöhte Gesamt-PSA-Werte. Bei 32,2 % der Teilnehmer zeigte sich mindestens ein kontrollbedürftiger Befund. Insgesamt wurden 6 Prostatabiopsien durchgeführt. Hierbei zeigte sich in einem Fall ein intermediate-risk Prostatakarzinom (Gleason 3 + 4, pT3a, pPn1, pNx, R0).
Schlussfolgerungung: Im Rahmen der UKF-Movember-Gesundheitsinitiative 2019 konnten durch ein Vorsorgeangebot 121 Männer für eine Prostatakrebs-Vorsorge inklusive PSA-Testung gewonnen werden. Auffällige/kontrollbedürftige Befunde zeigten sich bei 32,2 %. Bei einem Mitarbeiter wurde ein therapiebedürftiges Prostatakarzinom entdeckt und therapiert.
Barbagallo, Massimo ; Aberle, Oliver ; Alcayne, Victor ; Amaducci, Simone ; Andrzejewski, Józef ; Audouin, Laurent ; Babiano Suarez, Victor ; Bacak, Michael ; Bennett, Samuel ; Berthoumieux, Eric ; Bosnar, Damir ; Brown, Adam S. ; Busso, Maurizio ; Caamaño, Manuel ; Caballero Ontanaya, Luis ; Calviani, Marco ; Calviño Tavares, Francisco ; Cano-Ott, Daniel ; Casanovas Hoste, Adrià ; Cerutti, Francesco ; Chiaveri, Enrico ; Colonna, Nicola ; Cortés Rossell, Guillem Pere ; Cortés-Giraldo, Miguel Antonio ; Cosentino, Luigi ; Cristallo, Sergio ; Damone, Lucia Anna ; Davies, Paul John ; Diakaki, Maria ; Dietz, Mirco ; Domingo-Pardo, César ; Dressler, Rugard ; Ducasse, Quentin ; Dupont, Emmeric ; Durán, Ignacio ; Eleme, Zinovia ; Fernández Domínguez, Beatriz ; Ferrari, Alfredo ; Gonçalves, Isabel Maria Ferro ; Finocchiaro, Paolo ; Furman, Valter ; Garg, Ruchi ; Gawlik, Aleksandra ; Gilardoni, Simone ; Göbel, Kathrin ; González Romero, Enrique Miguel ; Guerrero Sánchez, Carlos ; Gunsing, Frank ; Heinitz, Stephan ; Heyse, Jan ; Jenkins, David ; Jericha, Erwin ; Jiri, U. ; Junghans, Arnd Rudolf ; Kadi, Yacine ; Käppeler, Franz ; Kimura, Atsushi ; Knapová, Ingrid ; Kokkoris, Michael ; Kopatch, Yuri N. ; Krtička, Milan ; Kurtulgil, Cem Deniz ; Ladarescu, Ion ; Lederer-Woods, Claudia ; Lerendegui-Marco, Jorge ; Lonsdale, Sarah-Jane ; Macina, Daniela ; Manna, Alice ; Martı́nez, Trinitario ; Masi, Alessandro ; Massimi, Cristian ; Mastinu, Pierfrancesco ; Mastromarco, Mario ; Maugeri, Emilio Andrea ; Mazzone, Annamaria ; Mendoza Cembranos, Emilio ; Mengoni, Alberto ; Michalopoulou, Veatriki ; Milazzo, Paolo Maria ; Millán Callado, María de los Ángeles ; Mingrone, Federica ; Moreno-Soto, Javier ; Musumarra, Agatino ; Negret, Alexandru ; Ogállar Ruiz, Francisco ; Oprea, Andreea ; Patronis, Nikolas ; Pavlik, Andreas ; Perkowski, Jarosław ; Petrone, Cristina ; Piersanti, Luciano ; Pirovano, Elisa ; Porras Sánchez, José Ignacio ; Praena, Javier ; Quesada Molina, José Manuel ; Ramos Doval, Diego ; Reifarth, René ; Rochman, Dimitri ; Rubbia, Carlo ; Sabaté- Gilarte, M. ; Saxena, Alok ; Schillebeeckx, Peter ; Schumann, Dorothea ; Sekhar, Adhitya ; Smith, Alastair Gavin ; Sosnin, Nikolay V. ; Sprung, Peter ; Stamatopoulos, Athanasios ; Tagliente, Giuseppe ; Taı́n Enríquez, José Luis ; Tarifeño-Saldivia, Ariel ; Tassan-Got, Laurent ; Thomas, Benedikt ; Torres-Sánchez, Pablo ; Tsinganis, Andrea ; Urlaß, Sebastian ; Valenta, Stanislav ; Vannini, Gianni ; Variale, Vincenzo ; Vaz, Pedro ; Ventura, Alberto ; Vescovi, Diego ; Vlachoudis, Vasilis ; Vlastou, Rosa ; Wallner, Anton ; Woods, Philip John ; Wright, Tobias J. ; Žugec, Petar
Although the 12C(n,p)12B and 12C(n,d)11B reactions are of interest in several fields of basic and applied Nuclear Physics the present knowledge of these two cross-sections is far from being accurate and reliable, with both evaluations and data showing sizable discrepancies. As part of the challenging n_TOF program on (n,cp) nuclear reactions study, the energy differential cross-sections of the 12C(n,p)12B and 12C(n,d)11 B reactions have been measured at CERN from the reaction thresholds up to 30 MeV neutron energy. Both measurements have been recently performed at the long flight-path (185 m) experimental area of the n_TOF facility at CERN using a pure (99.95%) rigid graphite target and two silicon telescopes. In this paper an overview of the experiment is presented together with a few preliminary results.
Görlich, Nina ; Brand, Hannah Antonia ; Langhans, Valerie ; Tesch, Sebastian ; Schachtner, Thomas ; Koch, Benjamin Florian ; Paliege, Alexander ; Schneider, Wolfgang ; Grützkau, Andreas ; Reinke, Petra ; Enghard, Philipp
Creatinine and proteinuria are used to monitor kidney transplant patients. However, renal biopsies are needed to diagnose renal graft rejection. Here, we assessed whether the quantification of different urinary cells would allow non-invasive detection of rejection. Urinary cell numbers of CD4+ and CD8+ T cells, monocytes/macrophages, tubular epithelial cells (TEC), and podocalyxin(PDX)-positive cells were determined using flow cytometry and were compared to biopsy results. Urine samples of 63 renal transplant patients were analyzed. Patients with transplant rejection had higher amounts of urinary T cells than controls; however, patients who showed worsening graft function without rejection had similar numbers of T cells. T cells correlated with histological findings (interstitial inflammation p = 0.0005, r = 0.70; tubulitis p = 0.006, r = 0.58). Combining the amount of urinary T cells and TEC, or T cells and PDX+ cells, yielded a significant segregation of patients with rejection from patients without rejection (all p < 0.01, area under the curve 0.89–0.91). Urinary cell populations analyzed by flow cytometry have the potential to introduce new monitoring methods for kidney transplant patients. The combination of urinary T cells, TEC, and PDX-positive cells may allow non-invasive detection of transplant rejection.
Won, Sae-Yeon ; Kilian, Andreas ; Dubinski, Daniel ; Geßler, Florian ; Dinc, Nazife ; Lauer, Monika ; Wolff, Robert Jürgen ; Freiman, Thomas Michael ; Senft, Christian ; Konczalla, Jürgen ; Forster, Marie-Therese ; Seifert, Volker
Purpose: Surgery of KOOS IV vestibular schwannoma remains challenging regarding the balance of extent of tumor resection (EoR) and functional outcome. Our aim was to evaluate the outcome of surgical resection and define a cut-off value for safe resection with low risk for tumor regrowth of KOOS IV vestibular schwannoma.
Methods: All patients presenting at the authors’ institution between 2000 and 2019 with surgically treated KOOS IV vestibular schwannoma were included. Outcome measures included EoR, facial/hearing nerve function, surgical complications and progression of residual tumor during the median follow-up period of 28 months.
Results: In 58 patients, mean tumor volume was 17.1 ± 9.2 cm3, and mean EoR of 81.6 ± 16.8% could be achieved. Fifty-one patients were available for the follow-up analysis. Growth of residual tumor was observed in 11 patients (21.6%) followed by adjuvant treatment with stereotactic radiosurgery or repeat surgery in 15 patients (29.4%). Overall serviceable hearing preservation was achieved in 38 patients (74.5%) and good facial outcome at discharge was observed in 66.7% of patients, significantly increasing to 82.4% at follow-up. Independent predictors for residual tumor growth was EoR ≤ 87% (OR11.1) with a higher EoR being associated with a very low number of residual tumor progression amounting to 7.1% at follow-up (p=0.008).
Conclusions: Subtotal tumor resection is a good therapeutic concept in patients with KOOS IV vestibular schwannoma resulting in a high rate of good hearing and facial nerve function and a very low rate of subsequent tumor progression. The goal of surgery should be to achieve more than 87% of tumor resection to keep residual tumor progression low.
Dropmann, Anne ; Dooley, Steven ; Dewidar, Bedair ; Hammad, Seddik ; Dediulia, Tatjana ; Werle, Julia ; Hartwig, Vanessa ; Ghafoory, Shahrouz ; Wölfl, Stefan ; Korhonen, Hanna ; Janicot, Michel ; Wosikowski, Katja ; Itzel, Timo ; Teufel, Andreas ; Schuppan, Detlef ; Stojanovic, Ana ; Cerwenka, Adelheid ; Nittka, Stefanie ; Piiper, Albrecht ; Gaiser, Timo ; Beraza, Naiara ; Milkiewicz, Malgorzata ; Milkiewicz, Piotr ; Brain, John G. ; Jones, David E. J. ; Weiss, Thomas S. ; Zanger, Ulrich M. ; Ebert, Matthias ; Meindl-Beinker, Nadja M.
Objective: TGF-β2 (TGF-β, transforming growth factor beta), the less-investigated sibling of TGF-β1, is deregulated in rodent and human liver diseases. Former data from bile duct ligated and MDR2 knockout (KO) mouse models for human cholestatic liver disease suggested an involvement of TGF-β2 in biliary-derived liver diseases.
Design: As we also found upregulated TGFB2 in liver tissue of patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), we now fathomed the positive prospects of targeting TGF-β2 in early stage biliary liver disease using the MDR2-KO mice. Specifically, the influence of TgfB2 silencing on the fibrotic and inflammatory niche was analysed on molecular, cellular and tissue levels.
Results: TgfB2-induced expression of fibrotic genes in cholangiocytes and hepatic stellate cellswas detected. TgfB2 expression in MDR2-KO mice was blunted using TgfB2-directed antisense oligonucleotides (AON). Upon AON treatment, reduced collagen deposition, hydroxyproline content and αSMA expression as well as induced PparG expression reflected a significant reduction of fibrogenesis without adverse effects on healthy livers. Expression analyses of fibrotic and inflammatory genes revealed AON-specific regulatory effects on Ccl3, Ccl4, Ccl5, Mki67 and Notch3 expression. Further, AON treatment of MDR2-KO mice increased tissue infiltration by F4/80-positive cells including eosinophils, whereas the number of CD45-positive inflammatory cells decreased. In line, TGFB2 and CD45 expression correlated positively in PSC/PBC patients and localised in similar areas of the diseased liver tissue.
Conclusions: Taken together, our data suggest a new mechanistic explanation for amelioration of fibrogenesis by TGF-β2 silencing and provide a direct rationale for TGF-β2-directed drug development.
Porto, Luciana ; You, Se-Jong ; Attarbaschi, Andishe ; Cario, Gunnar ; Döring, Michaela ; Moser, Olga ; Mücke, Urs ; Poyer, Fiona ; Temme, Christian ; Voigt, Sebastian ; Groll, Andreas H. ; Lauten, Melchior Johannes ; Hattingen, Elke ; Lehrnbecher, Thomas
Background: Due to the difficulties in the definite diagnosis, data on brain imaging in pediatric patients with central nervous system (CNS)-invasive mold infection (IMD) are scarce. Our aim was to describe brain imaging abnormalities seen in immunocompromised children with CNS-IMD, and to analyze retrospectively whether specific imaging findings and sequences have a prognostic value. Methods: In a retrospective study of 19 pediatric patients with proven or probable CNS-IMD, magnetic resonance imaging (MRI)-findings were described and analyzed. The results were correlated with outcome, namely death, severe sequelae, or no neurological sequelae. Results: 11 children and 8 adolescents (11/8 with proven/probable CNS-IMD) were included. Seven of the patients died and 12/19 children survived (63%): seven without major neurological sequelae and five with major neurological sequelae. Multifocal ring enhancement and diffusion restriction were the most common brain MRI changes. Diffusion restriction was mostly seen at the core of the lesion. No patient with disease limited to one lobe died. Perivascular microbleeding seen on susceptibility weighted imaging (SWI) and/or gradient-echo/T2* images, as well as infarction, were associated with poor prognosis. Conclusions: The presence of infarction was related to poor outcome. As early microbleeding seems to be associated with poor prognosis, we suggest including SWI in routine diagnostic evaluation of immunocompromised children with suspected CNS-IMD.
Pinter, Andreas ; Hoffmann, Matthias ; Reich, Kristian ; Augustin, Matthias ; Kaplan, Kadriye ; Gudjónsdóttir, Sigrún Dögg ; Delvin, Thomas ; Mrowietz, Ulrich
Background: Brodalumab is a fully human monoclonal immunoglobulin IgG2 antibody that binds to the human IL-17 receptor subunit A and by that inhibits the biologic action of IL-17A, IL-17F, IL-17C and IL-17E. Therapy with fumaric acid esters (FAE) is a well established and widely used first-line systemic treatment for subjects with moderate-to-severe plaque psoriasis. Objectives: To compare brodalumab to FAE in terms of clinical efficacy, patient-reported outcomes and safety in subjects with moderate-to-severe plaque psoriasis who were naïve to systemic treatment. Methods: Eligible subjects were randomized 1 : 1 to 210 mg brodalumab injections or oral FAE according to product label in this 24-week, open-label, assessor-blinded, multi-centre, head-to-head phase 4 trial. The primary endpoints were having PASI75 and having sPGA score of 0 or 1 (sPGA 0/1). Subjects with missing values for the primary endpoints were considered non-responders. Results: A total of 210 subjects were randomized. 91/105 subjects completed brodalumab treatment and 58/105 subjects completed FAE treatment. At Week 24, significantly more subjects in the brodalumab group compared to the FAE group had PASI75 (81.0% vs. 38.1%, P < 0.001) and sPGA 0/1 (64.8% vs. 20.0%, P < 0.001). In the brodalumab group, the median time to both PASI75 and to PASI90 was significantly shorter than in the FAE group (4.1 weeks vs. 16.4 weeks, and 7.4 weeks vs. 24.4 weeks, respectively, P < 0.0001 for both). The rate of adverse events was lower in subjects treated with brodalumab compared to subjects treated with FAE (616.4 vs. 1195.8 events per 100 exposure years). No new safety signals were detected for brodalumab. Conclusions: Brodalumab was associated with rapid and significant improvements in signs and symptoms of moderate-to-severe plaque psoriasis, with a superior efficacy profile to what was observed with FAE in systemic-naïve subjects over 24 weeks.
Binas, Oliver ; Jesus, Vanessa de ; Landgraf, Tom ; Völklein, Albrecht Eduard ; Martins, Jason ; Hymon, Daniel ; Bains, Jasleen Kaur ; Berg, Hannes ; Biedenbänder, Thomas ; Fürtig, Boris ; Gande, Santosh Lakshmi ; Niesteruk, Anna ; Oxenfarth, Andreas ; Qureshi, Nusrat ; Schamber, Tatjana ; Schnieders, Robbin ; Tröster, Alix Friederike ; Wacker, Anna ; Wirmer-Bartoschek, Julia ; Wirtz Martin, Maria Alexandra ; Stirnal, Elke ; Azzaoui, Kamal ; Richter, Christian ; Sreeramulu, Sridhar ; Blommers, Marcel Jules José ; Schwalbe, Harald
We report here the nuclear magnetic resonance 19F screening of 14 RNA targets with different secondary and tertiary structure to systematically assess the druggability of RNAs. Our RNA targets include representative bacterial riboswitches that naturally bind with nanomolar affinity and high specificity to cellular metabolites of low molecular weight. Based on counter-screens against five DNAs and five proteins, we can show that RNA can be specifically targeted. To demonstrate the quality of the initial fragment library that has been designed for easy follow-up chemistry, we further show how to increase binding affinity from an initial fragment hit by chemistry that links the identified fragment to the intercalator acridine. Thus, we achieve low-micromolar binding affinity without losing binding specificity between two different terminator structures.