@article{OPUS4-22691, title = {FCC-hh: The Hadron Collider: Future Circular Collider Conceptual Design Report Volume 3}, series = {European Physical Journal - Special Topics}, volume = {228}, journal = {European Physical Journal - Special Topics}, organization = {The FCC Collaboration}, doi = {10.1140/epjst/e2019-900087-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226917}, pages = {755-1107}, year = {2019}, abstract = {In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100TeV. Its unprecedented centre of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries.}, language = {en} } @article{OPUS4-22692, title = {HE-LHC: The High-Energy Large Hadron Collider : Future Circular Collider Conceptual Design Report Volume 4}, series = {European Physical Journal - Special Topics}, volume = {228}, journal = {European Physical Journal - Special Topics}, number = {5}, organization = {The FCC Collaboration}, doi = {10.1140/epjst/e2019-900088-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226928}, pages = {1109-1382}, year = {2019}, abstract = {In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries.}, language = {en} } @article{OPUS4-22693, title = {FCC Physics Opportunities: Future Circular Collider Conceptual Design Report Volume 1}, series = {European Physical Journal C}, volume = {79}, journal = {European Physical Journal C}, number = {474}, organization = {The FCC Collaboration}, doi = {10.1140/epjc/s10052-019-6904-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226938}, pages = {1-161}, year = {2019}, abstract = {We review the physics opportunities of the Future Circular Collider, covering its e(+)e(-), pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics.}, language = {en} } @article{NentwichRufGirschicketal.2019, author = {Nentwich, Julia and Ruf, Katharina and Girschick, Hermann and Holl-Wieden, Annette and Morbach, Henner and Hebestreit, Helge and Hofmann, Christine}, title = {Physical activity and health-related quality of life in chronic non-bacterial osteomyelitis}, series = {Pediatric Rheumatology}, volume = {17}, journal = {Pediatric Rheumatology}, doi = {10.1186/s12969-019-0351-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323710}, year = {2019}, abstract = {Background Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder of the skeletal system of yet unknown etiology. Patients present with local bone pain and inflammation and - to our experience - often suffer from functional impairment with significant disabilities of daily life. The objective of this study was to assess physical activity, fitness and health-related quality of life (HRQOL) in adolescents with established diagnosis of CNO versus healthy controls (HC). Methods 15 patients with CNO and 15 age and gender matched HC aged 13-18 years, completed questionnaires, performed an incremental exercise test with gas exchange measures up to voluntary fatigue and wore an accelerometer over 7 days at home to assess physical activity behavior. Results At the time of assessment, 5 CNO patients were in clinical, one in radiological and 5 in clinical and radiological remission. 7 did not receive any therapy at the time of assessment. The results of the exercise test and of the accelerometry did not show any significant difference between CNO and HC. However, reported sports participation was lower in patients with CNO and PedsQL3.0 and 4.0 showed significant lower values in most of the scores indicating reduced HRQOL. Conclusion Although most CNO patients showed a favorable course of disease without any relevant differences in objective measurements of physical activity and fitness versus HC at the time of assessment, questionnaires revealed perceived limitations. Further studies are needed to measure HRQOL and to validate questionnaires in patients with CNO against objective measures including more participants with a higher level of disease activity.}, language = {en} } @article{KleinertMuellerFuraijatetal.2019, author = {Kleinert, Evelyn and M{\"u}ller, Frank and Furaijat, Ghefar and Hillermann, Nele and Jablonka, Alexandra and Happle, Christine and Simmenroth, Anne}, title = {Does refugee status matter? Medical needs of newly arrived asylum seekers and resettlement refugees - a retrospective observational study of diagnoses in a primary care setting}, series = {Conflict and Health}, volume = {13}, journal = {Conflict and Health}, doi = {10.1186/s13031-019-0223-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325869}, year = {2019}, abstract = {Background Providing adequate healthcare to newly arrived refugees is considered one of the significant challenges for the German healthcare system. These refugees can be classified mainly into two groups: asylum seekers (who have applied for asylum after arrival in Germany and are waiting for the refugee-status decision) and resettlement refugees (who have already been granted asylum status before arriving in Germany). Whereas earlier studies have explored the health status of asylum seekers especially in terms of mental and behavioural disorders and infectious diseases without distinguishing between these two groups, our study aims to evaluate possible relationships of asylum status and medical needs of these two groups with a special focus on mental and behavioural disorders and infectious diseases. Methods In this retrospective observational study, collected data on all asylum-seeker and resettlement-refugee patients (N = 2252) of a German reception centre (August 2017 to August 2018) is analysed by absolute and relative frequencies and medians. Patient data, collected by chart review, include age, gender, country of origin, asylum status, and diagnoses (ICD-10). To describe the relationship between sociodemographic factors (including asylum status) and diagnoses, we used tests of significance and bivariate correlations with Spearman correlation coefficients. All collected data are pseudonymised. Results Of all 2252 patients, 43\% were resettlement refugees. In almost all ICD-10 categories, asylum seekers received significantly more diagnoses than resettlement refugees. According to our data, asylum seekers presented with mental and behavioural disorders nine times more often (9\%) than resettlement refugees (1\%). In the case of infectious diseases, the results are mixed: asylum seekers were twice as frequently (11\%) diagnosed with certain infectious and parasitic diseases than resettlement refugees (5\%), but resettlement refugees were treated twice as often (22\% of the asylum seekers and 41\% of the resettlement refugees) for diseases of the respiratory system, of which 84\% were acute respiratory infections (in both groups). Conclusion This study indicates that patients with unregulated migration more frequently present symptoms of psychiatric diseases and somatoform symptoms than resettlement refugees. A health policy approach within migration policy should aim to enable persecuted persons to migrate under regulated and safe conditions. Trial registration German Clinical Trials Register: DRKS00013076, retrospectively registered on 29.09.2017.}, language = {en} } @article{HinkelbeinIovinoDeRobertisetal.2019, author = {Hinkelbein, Jochen and Iovino, Ivan and De Robertis, Edoardo and Kranke, Peter}, title = {Outcomes in video laryngoscopy studies from 2007 to 2017: systematic review and analysis of primary and secondary endpoints for a core set of outcomes in video laryngoscopy research}, series = {BMC Anesthesiology}, volume = {19}, journal = {BMC Anesthesiology}, doi = {10.1186/s12871-019-0716-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320747}, year = {2019}, abstract = {Background Airway management is crucial and, probably, even the most important key competence in anaesthesiology, which directly influences patient safety and outcome. However, high-quality research is rarely published and studies usually have different primary or secondary endpoints which impedes clear unbiased comparisons between studies. The aim of the present study was to gather and analyse primary and secondary endpoints in video laryngoscopy studies being published over the last ten years and to create a core set of uniform or homogeneous outcomes (COS). Methods Retrospective analysis. Data were identified by using MEDLINE® database and the terms "video laryngoscopy" and "video laryngoscope" limited to the years 2007 to 2017. A total of 3351 studies were identified by the applied search strategy in PubMed. Papers were screened by two anaesthesiologists independently to identify study endpoints. The DELPHI method was used for consensus finding. Results In the 372 studies analysed and included, 49 different outcome categories/columns were reported. The items "time to intubation" (65.86\%), "laryngeal view grade" (44.89\%), "successful intubation rate" (36.56\%), "number of intubation attempts" (23.39\%), "complications" (21.24\%), and "successful first-pass intubation rate" (19.09\%) were reported most frequently. A total of 19 specific parameters is recommended. Conclusions In recent video laryngoscopy studies, many different and inhomogeneous parameters were used as outcome descriptors/endpoints. Based on these findings, we recommend that 19 specific parameters (e.g., "time to intubation" (inserting the laryngoscope to first ventilation), "laryngeal view grade" (C\&L and POGO), "successful intubation rate", etc.) should be used in coming research to facilitate future comparisons of video laryngoscopy studies.}, language = {en} } @article{HrudkaEisHeřmanetal.2019, author = {Hrudka, Jan and Eis, V{\´a}clav and Heřman, Josef and Prouzov{\´a}, Zuzana and Rosenwald, Andreas and František, Duška}, title = {Panniculitis-like T-cell-lymphoma in the mesentery associated with hemophagocytic syndrome: autopsy case report}, series = {Diagnostic Pathology}, volume = {14}, journal = {Diagnostic Pathology}, doi = {10.1186/s13000-019-0854-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322665}, year = {2019}, abstract = {Background Panniculitis-like T-cell lymphoma is an uncommon type of non-Hodgkin lymphoma, occurring usually in the form of nodules within the subcutaneous fat tissue of the extremities or trunk. In the literature, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is described as a distinct type of T-cell lymphoma with a variable clinical behavior, depending on molecular phenotype of T-cell receptor (TCR) and on the presence or absence of hemophagocytic syndrome. Case presentation We present a bioptic and autoptic case of a 65-years old Caucasian man with panniculitic T-cell lymphoma with morphological and immunohistochemical features of SPTCL, limited to the retroperitoneal and mesenteric mass, i.e. without any cutaneous involvement, and associated with severe hemophagocytic lymphohistiocytosis. Conclusion A panniculitic T-cell lymphoma with morphological and molecular features of SPTCL, which is limited to mesentery, i.e. does not involve subcutaneous fat, seems to be exceedingly rare.}, language = {en} } @article{CoelhoAlvesMonteiroetal.2019, author = {Coelho, Luis Pedro and Alves, Renato and Monteiro, Paulo and Huerta-Cepas, Jaime and Freitas, Ana Teresa and Bork, Peer}, title = {NG-meta-profiler: fast processing of metagenomes using NGLess, a domain-specific language}, series = {Microbiome}, volume = {7}, journal = {Microbiome}, number = {84}, doi = {10.1186/s40168-019-0684-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223161}, year = {2019}, abstract = {Background Shotgun metagenomes contain a sample of all the genomic material in an environment, allowing for the characterization of a microbial community. In order to understand these communities, bioinformatics methods are crucial. A common first step in processing metagenomes is to compute abundance estimates of different taxonomic or functional groups from the raw sequencing data. Given the breadth of the field, computational solutions need to be flexible and extensible, enabling the combination of different tools into a larger pipeline. Results We present NGLess and NG-meta-profiler. NGLess is a domain specific language for describing next-generation sequence processing pipelines. It was developed with the goal of enabling user-friendly computational reproducibility. It provides built-in support for many common operations on sequencing data and is extensible with external tools with configuration files. Using this framework, we developed NG-meta-profiler, a fast profiler for metagenomes which performs sequence preprocessing, mapping to bundled databases, filtering of the mapping results, and profiling (taxonomic and functional). It is significantly faster than either MOCAT2 or htseq-count and (as it builds on NGLess) its results are perfectly reproducible. Conclusions NG-meta-profiler is a high-performance solution for metagenomics processing built on NGLess. It can be used as-is to execute standard analyses or serve as the starting point for customization in a perfectly reproducible fashion. NGLess and NG-meta-profiler are open source software (under the liberal MIT license) and can be downloaded from https://ngless.embl.de or installed through bioconda.}, language = {en} } @article{deNijsChoeSteinbuschetal.2019, author = {de Nijs, Laurence and Choe, Kyonghwan and Steinbusch, Hellen and Schijns, Olaf E. M. G. and Dings, Jim and van den Hove, Daniel L. A. and Rutten, Bart P. F. and Hoogland, Govert}, title = {DNA methyltransferase isoforms expression in the temporal lobe of epilepsy patients with a history of febrile seizures}, series = {Clinical Epigenetics}, volume = {11}, journal = {Clinical Epigenetics}, doi = {10.1186/s13148-019-0721-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223636}, year = {2019}, abstract = {Background Temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) is a common pharmaco-resistant epilepsy referred for adult epilepsy surgery. Though associated with prolonged febrile seizures (FS) in childhood, the neurobiological basis for this relationship is not fully understood and currently no preventive or curative therapies are available. DNA methylation, an epigenetic mechanism catalyzed by DNA methyltransferases (DNMTs), potentially plays a pivotal role in epileptogenesis associated with FS. In an attempt to start exploring this notion, the present cross-sectional pilot study investigated whether global DNA methylation levels (5-mC and 5-hmC markers) and DNMT isoforms (DNMT1, DNMT3a1, and DNMT3a2) expression would be different in hippocampal and neocortical tissues between controls and TLE patients with or without a history of FS. Results We found that global DNA methylation levels and DNMT3a2 isoform expression were lower in the hippocampus for all TLE groups when compared to control patients, with a more significant decrease amongst the TLE groups with a history of FS. Interestingly, we showed that DNMT3a1 expression was severely diminished in the hippocampus of TLE patients with a history of FS in comparison with control and other TLE groups. In the neocortex, we found a higher expression of DNMT1 and DNMT3a1 as well as increased levels of global DNA methylation for all TLE patients compared to controls. Conclusion Together, the findings of this descriptive cross-sectional pilot study demonstrated brain region-specific changes in DNMT1 and DNMT3a isoform expression as well as global DNA methylation levels in human TLE with or without a history of FS. They highlighted a specific implication of DNMT3a isoforms in TLE after FS. Therefore, longitudinal studies that aim at targeting DNMT3a isoforms to evaluate the potential causal relationship between FS and TLE or treatment of FS-induced epileptogenesis seem warranted.}, language = {en} } @article{AbimannanSumathiKrishnarajasekharetal.2019, author = {Abimannan, Nagarajan and Sumathi, G. and Krishnarajasekhar, O. R. and Sinha, Bhanu and Krishnan, Padma}, title = {Clonal Clusters and Virulence Factors of Methicillin-Resistant \(Staphylococcus\) \(Aureus\): Evidence for Community-Acquired Methicillin-Resistant \(Staphylococcus\) \(Aureus\) Infiltration into Hospital Settings in Chennai, South India}, series = {Indian Journal of Medical Microbiology}, volume = {37}, journal = {Indian Journal of Medical Microbiology}, number = {3}, doi = {10.4103/ijmm.IJMM_18_271}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226963}, pages = {326-336}, year = {2019}, abstract = {Background and Objective: Staphylococcus aureus is one of the major pathogens of nosocomial infections as wells as community-acquired (CA) infections worldwide. So far, large-scale comprehensive molecular and epidemiological characterisation of S. aureus from very diverse settings has not been carried out in India. The objective of this study is to evaluate the molecular, epidemiological and virulence characteristics of S. aureus in both community and hospital settings in Chennai, southern India. Methods: S. aureus isolates were obtained from four different groups (a) healthy individuals from closed community settings, (b) inpatients from hospitals, (c) outpatients from hospitals, representing isolates of hospital-community interface and (d) HIV-infected patients to define isolates associated with the immunocompromised. Antibiotic susceptibility testing, multiplex polymerase chain reactions for detection of virulence and resistance determinants, molecular typing including Staphylococcal cassette chromosome mec (SCCmec) and agr typing, were carried out. Sequencing-based typing was done using spa and multilocus sequence typing (MLST) methods. Clonal complexes (CC) of hospital and CA methicillin-resistant S. aureus (MRSA) were identified and compared for virulence and resistance. Results and Conclusion: A total of 769 isolates of S. aureus isolates were studied. The prevalence of MRSA was found to be 7.17\%, 81.67\%, 58.33\% and 22.85\% for groups a, b, c and d, respectively. Of the four SCCmec types (I, III, IV and V) detected, SCCmec V was found to be predominant. Panton-Valentine leucocidin toxin genes were detected among MRSA isolates harbouring SCCmec IV and V. A total of 78 spa types were detected, t657 being the most prevalent. 13 MLST types belonging to 9 CC were detected. CC1 (ST-772, ST-1) and CC8 (ST238, ST368 and ST1208) were found to be predominant among MRSA. CA-MRSA isolates with SCCmec IV and V were isolated from all study groups including hospitalised patients and were found to be similar by molecular tools. This shows that CA MRSA has probably infiltrated into the hospital settings.}, language = {en} } @article{OPUS4-22694, title = {FCC-ee: The Lepton Collider: Future Circular Collider Conceptual Design Report Volume 2}, series = {European Physical Journal - Special Topics}, volume = {228}, journal = {European Physical Journal - Special Topics}, number = {2}, organization = {The FCC Collaboration}, doi = {10.1140/epjst/e2019-900045-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226947}, pages = {261-623}, year = {2019}, abstract = {In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today's technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics.}, language = {en} } @article{HetzerOrthHoellerWuerzneretal.2019, author = {Hetzer, Benjamin and Orth-H{\"o}ller, Dorothea and W{\"u}rzner, Reinhard and Kreidl, Peter and Lackner, Michaela and M{\"u}ller, Thomas and Knabl, Ludwig and Geisler-Moroder, Daniel Rudolf and Mellmann, Alexander and Sesli, {\"O}zcan and Holzknecht, Jeanett and Noce, Damia and Akarathum, Noppadon and Chotinaruemol, Somporn and Prelog, Martina and Oberdorfer, Peninnah}, title = {"Enhanced acquisition of antibiotic-resistant intestinal E. coli during the first year of life assessed in a prospective cohort study"}, series = {Antimicrobial Resistance \& Infection Control}, volume = {8}, journal = {Antimicrobial Resistance \& Infection Control}, doi = {10.1186/s13756-019-0522-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320284}, year = {2019}, abstract = {Background Increasing bacterial resistance to antibiotics is a serious problem worldwide. We sought to record the acquisition of antibiotic-resistant Escherichia coli (E. coli) in healthy infants in Northern Thailand and investigated potential determinants. Methods Stool samples from 142 infants after birth, at ages 2wk, 2mo, 4 to 6mo, and 1y, and parent stool samples were screened for E. coli resistance to tetracycline, ampicillin, co-trimoxazole, and cefazoline by culture, and isolates were further investigated for multiresistance by disc diffusion method. Pulsed-field gel electrophoresis was performed to identify persistent and transmitted strains. Genetic comparison of resistant and transmitted strains was done by multilocus sequence typing (MLST) and strains were further investigated for extra- and intra-intestinal virulence factors by multiplex PCR. Results Forty-seven (33\%) neonatal meconium samples contained resistant E. coli. Prevalence increased continuously: After 1y, resistance proportion (tetracycline 80\%, ampicillin 72\%, co-trimoxazole 66\%, cefazoline 35\%) almost matched those in parents. In 8 infants (6\%), identical E. coli strains were found in at least 3 sampling time points (suggesting persistence). Transmission of resistant E. coli from parents to child was observed in only 8 families. MLST showed high diversity. We could not identify any virulence genes or factors associated with persistence, or transmission of resistant E. coli. Full-term, vaginal birth and birth in rural hospital were identified as risk factors for early childhood colonization with resistant E. coli. Conclusion One third of healthy Thai neonates harboured antibiotic-resistant E. coli in meconium. The proportion of resistant E. coli increased during the first year of life almost reaching the value in adults. We hypothesize that enhancement of infection control measures and cautious use of antibiotics may help to control further increase of resistance.}, language = {en} } @article{MoremiClausVogeletal.2019, author = {Moremi, Nyambura and Claus, Heike and Vogel, Ulrich and Mshana, Stephen E.}, title = {The role of patients and healthcare workers Staphylococcus aureus nasal colonization in occurrence of surgical site infection among patients admitted in two centers in Tanzania}, series = {Antimicrobial Resistance \& Infection Control}, volume = {8}, journal = {Antimicrobial Resistance \& Infection Control}, doi = {10.1186/s13756-019-0554-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224185}, year = {2019}, abstract = {Background Colonization with Staphylococcus aureus has been identified as a risk for subsequent occurrence of infection. This study investigated the relationship between S. aureus colonization of patients and healthcare workers (HCWs), and subsequent surgical site infections (SSI). Methods Between December 2014 and September 2015, a total of 930 patients and 143 HCWs were enrolled from the Bugando Medical Centre and Sekou Toure hospital in Mwanza, Tanzania. On admission and discharge nasal swabs, with an additional of wound swab for those who developed SSI were collected from patients whereas HCWs were swabbed once. Identification and antimicrobial susceptibility testing were done by VITEK-MS and VITEK-2, respectively. Detection of Panton Valentine leukocidin (PVL) and mecA genes was done by PCR. S. aureus isolates were further characterized by spa typing and Multi-Locus Sequence Typing (MLST). Results Among 930 patients screened for S. aureus on admission, 129 (13.9\%) were positive of which 5.4\% (7/129) were methicillin-resistant S. aureus (MRSA). Amongst 363 patients rescreened on discharge, 301 patients had been tested negative on admission of whom 29 (9.6\%) turned positive after their hospital stay. Three (10.3\%) of the 29 acquired S. aureus were MRSA. Inducible Clindamycin resistance occurred more often among acquired S. aureus isolates than among isolates from admission [34.5\% (10/29) vs. 17.1\% (22/129), P = 0.018]. S. aureus contributed to 21.1\% (n = 12) of the 57 cases of investigated SSIs among 536 patients followed. Seven out of eight S. aureus carriage/infection pairs had the same spa and sequence types. The previously reported dominant PVL-positive ST88 MRSA strain with spa type t690 was detected in patients and HCW. Conclusion A significant proportion of patients acquired S. aureus during hospitalization. The finding of more than 90\% of S. aureus SSI to be of endogenous source underscores the need of improving infection prevention and control measures including screening and decolonization of high risk patients.}, language = {en} } @article{BrumbergBlazhenetsSchroeteretal.2019, author = {Brumberg, Joachim and Blazhenets, Ganna and Schr{\"o}ter, Nils and Frings, Lars and Jost, Wolfgang H. and Lapa, Constantin and Meyer, Philipp T.}, title = {Imaging cardiac sympathetic innervation with MIBG: linear conversion of the heart-to-mediastinum ratio between different collimators}, series = {EJNMMI Physics}, volume = {6}, journal = {EJNMMI Physics}, doi = {10.1186/s40658-019-0250-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221675}, year = {2019}, abstract = {Background The heart-to-mediastinum (H/M) ratio is a commonly used parameter to measure cardiac I-123 metaiodobenzylguanidine (MIBG) uptake. Since the H/M ratio is substantially influenced by the collimator type, we investigated whether an empirical linear conversion of H/M ratios between camera systems with low-energy (LE) and medium-energy (ME) collimator is possible. Methods We included 18 patients with parkinsonism who were referred to one of the two participating molecular imaging facilities for the evaluation of cardiac sympathetic innervation by MIBG scintigraphy. Two consecutive planar image datasets were acquired with LE and ME collimators at 4 h after MIBG administration. Linear regression analyses were performed to describe the association between the H/M ratios gained with both collimator settings, and the accuracy of a linear transfer of the H/M ratio between collimators and across centers was assessed using a leave-one-out procedure. Results H/M ratios acquired with LE and ME collimators showed a strong linear relationship both within each imaging facility (R\(^2\) = 0.99, p < 0.001 and R\(^2\) = 0.90, p < 0.001) and across centers (H/M-LE = 0.41 × H/M-ME + 0.63, R\(^2\) = 0.97, p < 0.001). A linear conversion of H/M ratios between collimators and across centers was estimated to be very accurate (mean absolute error 0.05 ± 0.04; mean relative absolute error 3.2 ± 2.6\%). Conclusions The present study demonstrates that a simple linear conversion of H/M ratios acquired with different collimators is possible with high accuracy. This should greatly facilitate the exchange of normative data between settings and pooling of data from different institutions.}, language = {en} } @article{KienerChenKrebsetal.2019, author = {Kiener, Mirjam and Chen, Lanpeng and Krebs, Markus and Grosjean, Joȅl and Klima, Irena and Kalogirou, Charis and Riedmiller, Hubertus and Kneitz, Burkhard and Thalmann, George N. and Snaar-Jagalska, Ewa and Spahn, Martin and Kruithof-de Julio, Marianna and Zoni, Eugenio}, title = {miR-221-5p regulates proliferation and migration in human prostate cancer cells and reduces tumor growth in vivo}, series = {BMC Cancer}, volume = {19}, journal = {BMC Cancer}, doi = {10.1186/s12885-019-5819-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325762}, year = {2019}, abstract = {Background Despite latest advances in prostate cancer (PCa) therapy, PCa remains the third-leading cause of cancer-related death in European men. Dysregulation of microRNAs (miRNAs), small non-coding RNA molecules with gene expression regulatory function, has been reported in all types of epithelial and haematological cancers. In particular, miR-221-5p alterations have been reported in PCa. Methods miRNA expression data was retrieved from a comprehensive publicly available dataset of 218 PCa patients (GSE21036) and miR-221-5p expression levels were analysed. The functional role of miR-221-5p was characterised in androgen- dependent and androgen- independent PCa cell line models (C4-2 and PC-3M-Pro4 cells) by miR-221-5p overexpression and knock-down experiments. The metastatic potential of highly aggressive PC-3M-Pro4 cells overexpressing miR-221-5p was determined by studying extravasation in a zebrafish model. Finally, the effect of miR-221-5p overexpression on the growth of PC-3M-Pro4luc2 cells in vivo was studied by orthotopic implantation in male Balb/cByJ nude mice and assessment of tumor growth. Results Analysis of microRNA expression dataset for human primary and metastatic PCa samples and control normal adjacent benign prostate revealed miR-221-5p to be significantly downregulated in PCa compared to normal prostate tissue and in metastasis compared to primary PCa. Our in vitro data suggest that miR-221-5p overexpression reduced PCa cell proliferation and colony formation. Furthermore, miR-221-5p overexpression dramatically reduced migration of PCa cells, which was associated with differential expression of selected EMT markers. The functional changes of miR-221-5p overexpression were reversible by the loss of miR-221-5p levels, indicating that the tumor suppressive effects were specific to miR-221-5p. Additionally, miR-221-5p overexpression significantly reduced PC-3M-Pro4 cell extravasation and metastasis formation in a zebrafish model and decreased tumor burden in an orthotopic mouse model of PCa. Conclusions Together these data strongly support a tumor suppressive role of miR-221-5p in the context of PCa and its potential as therapeutic target.}, language = {en} } @article{KlementAbbasiSengerAdebahretal.2019, author = {Klement, Rainer J. and Abbasi-Senger, N. and Adebahr, S. and Alheid, H. and Allgaeuer, M. and Becker, G. and Blanck, O. and Boda-Heggemann, J. and Brunner, T. and Duma, M. and Eble, M. J. and Ernst, I. and Gerum, S. and Habermehl, D. and Hass, P. and Henkenberens, C. and Hildebrandt, G. and Imhoff, D. and Kahl, H. and Klass, N. D. and Krempien, R. and Lewitzki, V. and Lohaus, F. and Ostheimer, C. and Papachristofilou, A. and Petersen, C. and Rieber, J. and Schneider, T. and Schrade, E. and Semrau, R. and Wachter, S. and Wittig, A. and Guckenberger, M. and Andratschke, N.}, title = {The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases}, series = {BMC Cancer}, volume = {19}, journal = {BMC Cancer}, doi = {10.1186/s12885-019-5362-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325877}, year = {2019}, abstract = {Background The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. Methods The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. Results Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. Conclusion In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.}, language = {en} } @article{HoertererBaumbachLemperleetal.2019, author = {H{\"o}rterer, Hubert and Baumbach, Sebastian Felix and Lemperle, Stefan and Altenberger, Sebastian and Gottschalk, Oliver and Mehlhorn, Alexander Tobias and R{\"o}ser, Anke and Walther, Markus}, title = {Clinical outcome and concomitant injuries in operatively treated fractures of the lateral process of the talus}, series = {BMC Musculoskeletal Disorders}, volume = {20}, journal = {BMC Musculoskeletal Disorders}, doi = {10.1186/s12891-019-2603-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321207}, year = {2019}, abstract = {Background The aim of this study was to review the patient rated outcome (PROM) of surgically treated fractures to the lateral process of the talus (LPTF) and identify factors influencing the outcome. Methods Retrospective study with a current follow-up. Eligible were all patients treated surgically for a LPTF (n = 23) with a minimum follow-up of one year. Demographics, medical history, trauma mechanism, fracture characteristics, concomitant injuries, treatment details, complications, return to work and sports were assessed retrospectively. The current follow-up included the VAS FA, Karlsson Score, and SF-12. The primary outcome was the VAS FA. Secondary aim was the identification of parameters influencing the PROMs. Results 22 patients (96\% follow-up) with a mean age of 32 ± 9 (18 to 49) years were included. 73\% suffered a Hawkins Type 1, 23\% a Type 2, and one patient a Type 3 fracture. 82\% suffered concomitant injuries. 9\% suffered minor surgical side infections, 50\% developed symptomatic subtalar osteoarthritis. At final follow-up (44 ± 2 (12 to 97) months), the mean VAS FA Overall was 77 ± 21 (20 to 100), the Karlsson Score 72 ± 21 (34 to 97), and for the SF 12 the PCS 53 ± 8 (36 to 64) and the MCS 53 ± 7 (32 to 63). 50\% of patients returned to their previous level of sports. Hawkins Type 1 fractures resulted in better VAS FA Overall score than Type 2 fractures. Posttraumatic subtalar osteoarthritis was the independent factor associated to a poor patient rated outcome (VAS FA, Karlsson Score). Conclusion After a follow-up of over 3.5 years, surgically treated LPTF resulted in only moderate results. 50\% suffered posttraumatic symptomatic subtalar osteoarthritis, which was the primary independent parameter for a poor outcome following LPTF. Level of evidence Level III.}, language = {en} } @article{AlbertAndreAnghinolfietal.2019, author = {Albert, A. and Andr{\´e}, M. and Anghinolfi, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Aublin, J. and Avgitas, T. and Baret, B. and Barrios-Mart{\´i}t, J. and Basa, S. and Belhorma, B. and Bertin, V. and Biagi, S. and Bormuth, R. and Boumaaza, J and Bourret, S. and Bouwhuis, M. C. and Br{\^a}nzas, H. and Bruijn, R. and Brunner, J. and Busto, J. and Capone, A. and Caramete, L. and Carr, J. and Celli, S. and Chabab, M. and Cherkaoui El Moursli, R. and Chiarusi, T. and Circella, M. and Coelho, J. A. B. and Coleiro, A. and Colomer, M and Coniglione, R. and Costantini, H. and Coyle, P. and Creusot, A. and D{\´i}az, A. F. and Deschamps, A. and Distefano, C. and Di Palma, I. and Domi, A. and Donzaud, C. and Dornic, D. and Drouhin, D. and Eberl, T. and El Bojaddaini, I. and El Khayati, N. and Els{\"a}sser, D. and Enzenh{\"o}fer, A. and Ettahiri, A. and Fassi, F. and Felis, I. and Fermani, P. and Ferrara, G. and Fusco, L. A. and Gay, P. and Glotin, H. and Gr{\´e}goire, T. and Gracia Ruiz, R. and Graf, K. and Hallmann, S. and van Haren, H. and Heijboer, A. J. and Hello, Y. and Hern{\´a}ndez-Rey, J. J. and H{\"o}ßl, J. and Hofest{\"a}dt, J. and Illuminati, G. and de Jong, M. and Jongen, M. and Kadler, M. and Kalekin, O. and Katz, U. and Khan-Chowdhury, N. R. and Kouchner, A. and Kreter, M. and Kreykenbohm, I. and Kulikovskiy, V. and Lachaud, C. and Lahmann, R. and Lef{\`e}vre, D. and Leonora, E. and Levi, G. and Lotze, M. and Loucatos, S. and Marcelin, M. and Margiotta, A. and Marinelli, A. and Mart{\´i}nez-Mora, J. A. and Mele, R. and Melis, K. and Migliozzi, P. and Moussa, A. and Navas, S. and Nezri, E. and Nu{\~n}ez, A. and Organokov, M. and Pavalas, G. E. and Pellegrino, C. and Piattelli, P. and Popa, V. and Pradier, T. and Quinn, L. and Racca, C. and Randazzo, N. and Riccobene, G. and S{\´a}nchez-Losa, A. and Salda{\~n}a, M. and Salvadori, I. and Samtleben, D. F. E. and Sanguineti, M. and Sapienza, P. and Sch{\"u}ssler, F. and Spurio, M. and Stolarczyk, Th. and Taiuti, M. and Tayalati, Y. and Trovato, A. and Vallage, B. and Van Elewyck, V. and Versari, F. and Vivolo, D. and Wilms, J. and Zaborov, D. and Zornoza, J. D. and Z{\´u}{\~n}iga, J.}, title = {The cosmic ray shadow of the Moon observed with the ANTARES neutrino telescope}, series = {European Physical Journal C}, volume = {78}, journal = {European Physical Journal C}, doi = {10.1140/epjc/s10052-018-6451-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227802}, pages = {1-9}, year = {2019}, abstract = {One of the main objectives of the ANTARES telescope is the search for point- like neutrino sources. Both the pointing accuracy and the angular resolution of the detector are important in this context and a reliableway to evaluate this performance is needed. In order to measure the pointing accuracy of the detector, one possibility is to study the shadow of the Moon, i. e. the deficit of the atmospheric muon flux from the direction of the Moon induced by the absorption of cosmic rays. Analysing the data taken between 2007 and 2016, theMoon shadow is observed with 3.5s statistical significance. The detector angular resolution for downwardgoing muons is 0.73. +/- 0.14.. The resulting pointing performance is consistent with the expectations. An independent check of the telescope pointing accuracy is realised with the data collected by a shower array detector onboard of a ship temporarily moving around the ANTARES location.}, language = {en} } @article{AlacevichCarloniCalameChiesaetal.2019, author = {Alacevich, Massimo and Carloni Calame, Carlo M. and Chiesa, Mauro and Montagna, Guido and Nicrosini, Oreste and Piccinini, Fulvio}, title = {Muon-electron scattering at NLO}, series = {Journal of High Energy Physics}, volume = {155}, journal = {Journal of High Energy Physics}, number = {2}, doi = {10.1007/JHEP02(2019)155}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227777}, pages = {1-25}, year = {2019}, abstract = {We consider the process of muon-electron elastic scattering, which has been proposed as an ideal framework to measure the running of the electromagnetic coupling constant at space-like momenta and determine the leading-order hadronic contribution to the muon g-2 (MUonE experiment). We compute the next-to-leading (NLO) contributions due to QED and purely weak corrections and implement them into a fully differential Monte Carlo event generator, which is available for first experimental studies. We show representative phenomenological results of interest for the MUonE experiment and examine in detail the impact of the various sources of radiative corrections under different selection criteria, in order to study the dependence of the NLO contributions on the applied cuts. The study represents the first step towards the realisation of a high-precision Monte Carlo code necessary for data analysis.}, language = {en} } @article{AktasUpcinHenkeetal.2019, author = {Aktas, Bertal H. and Upcin, Berin and Henke, Erik and Padmasekar, Manju and Qin, Xuebin and Erg{\"u}n, S{\"u}leyman}, title = {The Best for the Most Important: Maintaining a Pristine Proteome in Stem and Progenitor Cells}, series = {Stem Cells International}, journal = {Stem Cells International}, doi = {10.1155/2019/1608787}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227769}, pages = {1-20}, year = {2019}, abstract = {Pluripotent stem cells give rise to reproductively enabled offsprings by generating progressively lineage-restricted multipotent stem cells that would differentiate into lineage-committed stem and progenitor cells. These lineage-committed stem and progenitor cells give rise to all adult tissues and organs. Adult stem and progenitor cells are generated as part of the developmental program and play critical roles in tissue and organ maintenance and/or regeneration. The ability of pluripotent stem cells to self-renew, maintain pluripotency, and differentiate into a multicellular organism is highly dependent on sensing and integrating extracellular and extraorganismal cues. Proteins perform and integrate almost all cellular functions including signal transduction, regulation of gene expression, metabolism, and cell division and death. Therefore, maintenance of an appropriate mix of correctly folded proteins, a pristine proteome, is essential for proper stem cell function. The stem cells' proteome must be pristine because unfolded, misfolded, or otherwise damaged proteins would interfere with unlimited self-renewal, maintenance of pluripotency, differentiation into downstream lineages, and consequently with the development of properly functioning tissue and organs. Understanding how various stem cells generate and maintain a pristine proteome is therefore essential for exploiting their potential in regenerative medicine and possibly for the discovery of novel approaches for maintaining, propagating, and differentiating pluripotent, multipotent, and adult stem cells as well as induced pluripotent stem cells. In this review, we will summarize cellular networks used by various stem cells for generation and maintenance of a pristine proteome. We will also explore the coordination of these networks with one another and their integration with the gene regulatory and signaling networks.}, language = {en} }