TY - JOUR
A1 - Reiners, Philipp
A1 - Asam, Sarah
A1 - Frey, Corinne
A1 - Holzwarth, Stefanie
A1 - Bachmann, Martin
A1 - Sobrino, Jose
A1 - Göttsche, Frank-M.
A1 - Bendix, Jörg
A1 - Kuenzer, Claudia
T1 - Validation of AVHRR Land Surface Temperature with MODIS and in situ LST — a TIMELINE thematic processor
JF - Remote Sensing
N2 - Land Surface Temperature (LST) is an important parameter for tracing the impact of changing climatic conditions on our environment. Describing the interface between long- and shortwave radiation fluxes, as well as between turbulent heat fluxes and the ground heat flux, LST plays a crucial role in the global heat balance. Satellite-derived LST is an indispensable tool for monitoring these changes consistently over large areas and for long time periods. Data from the AVHRR (Advanced Very High-Resolution Radiometer) sensors have been available since the early 1980s. In the TIMELINE project, LST is derived for the entire operating period of AVHRR sensors over Europe at a 1 km spatial resolution. In this study, we present the validation results for the TIMELINE AVHRR daytime LST. The validation approach consists of an assessment of the temporal consistency of the AVHRR LST time series, an inter-comparison between AVHRR LST and in situ LST, and a comparison of the AVHRR LST product with concurrent MODIS (Moderate Resolution Imaging Spectroradiometer) LST. The results indicate the successful derivation of stable LST time series from multi-decadal AVHRR data. The validation results were investigated regarding different LST, TCWV and VA, as well as land cover classes. The comparisons between the TIMELINE LST product and the reference datasets show seasonal and land cover-related patterns. The LST level was found to be the most determinative factor of the error. On average, an absolute deviation of the AVHRR LST by 1.83 K from in situ LST, as well as a difference of 2.34 K from the MODIS product, was observed.
KW - Land Surface Temperature
KW - AVHRR
KW - MODIS
KW - time series
KW - Europe
KW - validation
KW - TIMELINE
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246051
SN - 2072-4292
VL - 13
IS - 17
ER -
TY - JOUR
A1 - Shan, Junwen
A1 - Böck, Thomas
A1 - Keller, Thorsten
A1 - Forster, Leonard
A1 - Blunk, Torsten
A1 - Groll, Jürgen
A1 - Teßmar, Jörg
T1 - TEMPO/TCC as a Chemo Selective Alternative for the Oxidation of Hyaluronic Acid
JF - Molecules
N2 - Hyaluronic acid (HA)-based hydrogels are very commonly applied as cell carriers for different approaches in regenerative medicine. HA itself is a well-studied biomolecule that originates from the physiological extracellular matrix (ECM) of mammalians and, due to its acidic polysaccharide structure, offers many different possibilities for suitable chemical modifications which are necessary to control, for example, network formation. Most of these chemical modifications are performed using the free acid function of the polymer and, additionally, lead to an undesirable breakdown of the biopolymer’s backbone. An alternative modification of the vicinal diol of the glucuronic acid is oxidation with sodium periodate to generate dialdehydes via a ring opening mechanism that can subsequently be further modified or crosslinked via Schiff base chemistry. Since this oxidation causes a structural destruction of the polysaccharide backbone, it was our intention to study a novel synthesis protocol frequently applied to selectively oxidize the C6 hydroxyl group of saccharides. On the basis of this TEMPO/TCC oxidation, we studied an alternative hydrogel platform based on oxidized HA crosslinked using adipic acid dihydrazide as the crosslinker.
KW - hyaluronic acid
KW - oxidation
KW - hydrogel formation
KW - Schiff base chemistry
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248362
SN - 1420-3049
VL - 26
IS - 19
ER -
TY - JOUR
A1 - Schlevogt, Bernhard
A1 - Boeker, Klaus H. W.
A1 - Mauss, Stefan
A1 - Klinker, Hartwig
A1 - Heyne, Renate
A1 - Link, Ralph
A1 - Simon, Karl-Georg
A1 - Sarrazin, Christoph
A1 - Serfert, Yvonne
A1 - Manns, Michael P.
A1 - Wedemeyer, Heiner
T1 - Weight gain after interferon-free treatment of chronic hepatitis C — results from the German Hepatitis C-Registry (DHC-R)
JF - Biomedicines
N2 - Chronic hepatitis C can be treated very effectively with direct-acting antivirals (DAA) with only minor side effects compared to an interferon-containing treatment regimen. The significance of metabolic comorbidities after HCV cure is not well defined. This study aims to investigate short- and long-term weight change of patients receiving interferon-free antiviral treatment for chronic hepatitis C. The German Hepatitis C-registry (DHC-R) is a national multicenter real-world cohort. A total of 5111 patients were followed prospectively after DAA treatment for up to 3 years. Weight change compared to baseline was analyzed at end of treatment and at years 1, 2, and 3 after completion of antiviral therapy. Regression analysis was performed to identify baseline predictors for weight change. While there was no relevant mean weight change (−0.2 kg, SD 4.3 kg) at the end of antiviral treatment, weight started to increase during long-term follow-up reaching +1.7 kg (SD 8.0 kg, p < 0.001) compared to baseline at 3 years (follow-up year 3, FU3) after completion of antiviral therapy. 48%, 31%, and 22% of patients had a weight gain greater than 1, 3, and 5 kg at FU3, respectively. During follow-up, a body mass index (BMI) <30 proved to be the only consistent predictor for weight gain. DAA treatment is followed by a substantial weight gain (+3 kg or more) in one-third of the patients during long-term follow-up. Non-obese patients seemed to be most vulnerable to weight gain. The body compartment involved in weight gain as well as the mechanism of weight gain remain to be elucidated.
KW - chronic hepatitis C
KW - direct-acting antivirals
KW - interferon-free
KW - HCV cure
KW - weight gain
KW - German Hepatitis C-Registry
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248476
SN - 2227-9059
VL - 9
IS - 10
ER -
TY - JOUR
A1 - Koch, Elias A. T.
A1 - Petzold, Anne
A1 - Wessely, Anja
A1 - Dippel, Edgar
A1 - Gesierich, Anja
A1 - Gutzmer, Ralf
A1 - Hassel, Jessica C.
A1 - Haferkamp, Sebastian
A1 - Hohberger, Bettina
A1 - Kähler, Katharina C.
A1 - Knorr, Harald
A1 - Kreuzberg, Nicole
A1 - Leiter, Ulrike
A1 - Loquai, Carmen
A1 - Meier, Friedegund
A1 - Meissner, Markus
A1 - Mohr, Peter
A1 - Pföhler, Claudia
A1 - Rahimi, Farnaz
A1 - Schadendorf, Dirk
A1 - Schell, Beatrice
A1 - Schlaak, Max
A1 - Terheyden, Patrick
A1 - Thoms, Kai-Martin
A1 - Schuler-Thurner, Beatrice
A1 - Ugurel, Selma
A1 - Ulrich, Jens
A1 - Utikal, Jochen
A1 - Weichenthal, Michael
A1 - Ziller, Fabian
A1 - Berking, Carola
A1 - Heppt, Markus
T1 - Immune checkpoint blockade for metastatic uveal melanoma: patterns of response and survival according to the presence of hepatic and extrahepatic metastasis
JF - Cancers
N2 - Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan–Meier method. Log-rank tests, χ\(^2\) tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95% CI 13.4–23.7) and the median PFS, 2.8 months (95% CI 2.5–3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8% and to anti-PD-1 monotherapy 8.9% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7% vs. cohort B 16.7%; p = 0.45). Adverse events (AE) occurred in 41.6%. Severe AE were observed in 26.3% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.
KW - uveal melanoma
KW - immune checkpoint blockade
KW - PD-1
KW - CTLA-4
KW - liver metastasis
KW - treatment resistance
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242603
SN - 2072-6694
VL - 13
IS - 13
ER -
TY - JOUR
A1 - Opolka, Alexander
A1 - Müller, Dominik
A1 - Fella, Christian
A1 - Balles, Andreas
A1 - Mohr, Jürgen
A1 - Last, Arndt
T1 - Multi-lens array full-field X-ray microscopy
JF - Applied Sciences
N2 - X-ray full-field microscopy at laboratory sources for photon energies above 10 keV suffers from either long exposure times or low resolution. The photon flux is mainly limited by the objectives used, having a limited numerical aperture NA. We show that this can be overcome by making use of the cone-beam illumination of laboratory sources by imaging the same field of view (FoV) several times under slightly different angles using an array of X-ray lenses. Using this technique, the exposure time can be reduced drastically without any loss in terms of resolution. A proof-of-principle is given using an existing laboratory metal-jet source at the 9.25 keV Ga K\(_α\)-line and compared to a ray-tracing simulation of the setup.
KW - X-ray microscopy
KW - full-field microscopy
KW - compound refractive X-ray lenses
KW - CRLs
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244974
SN - 2076-3417
VL - 11
IS - 16
ER -
TY - JOUR
A1 - Brunkhorst-Kanaan, Nathalie
A1 - Trautmann, Sandra
A1 - Schreiber, Yannick
A1 - Thomas, Dominique
A1 - Kittel-Schneider, Sarah
A1 - Gurke, Robert
A1 - Geisslinger, Gerd
A1 - Reif, Andreas
A1 - Tegeder, Irmgard
T1 - Sphingolipid and endocannabinoid profiles in adult attention deficit hyperactivity disorder
JF - Biomedicines
N2 - Genes encoding endocannabinoid and sphingolipid metabolism pathways were suggested to contribute to the genetic risk towards attention deficit hyperactivity disorder (ADHD). The present pilot study assessed plasma concentrations of candidate endocannabinoids, sphingolipids and ceramides in individuals with adult ADHD in comparison with healthy controls and patients with affective disorders. Targeted lipid analyses of 23 different lipid species were performed in 71 mental disorder patients and 98 healthy controls (HC). The patients were diagnosed with adult ADHD (n = 12), affective disorder (major depression, MD n = 16 or bipolar disorder, BD n = 6) or adult ADHD with comorbid affective disorders (n = 37). Canonical discriminant analysis and CHAID analyses were used to identify major components that predicted the diagnostic group. ADHD patients had increased plasma concentrations of sphingosine-1-phosphate (S1P d18:1) and sphinganine-1-phosphate (S1P d18:0). In addition, the endocannabinoids, anandamide (AEA) and arachidonoylglycerol were increased. MD/BD patients had increased long chain ceramides, most prominently Cer22:0, but low endocannabinoids in contrast to ADHD patients. Patients with ADHD and comorbid affective disorders displayed increased S1P d18:1 and increased Cer22:0, but the individual lipid levels were lower than in the non-comorbid disorders. Sphingolipid profiles differ between patients suffering from ADHD and affective disorders, with overlapping patterns in comorbid patients. The S1P d18:1 to Cer22:0 ratio may constitute a diagnostic or prognostic tool.
KW - attention deficit hyperactivity disorder
KW - endocannabinoids
KW - ceramides
KW - bipolar disorder
KW - major depression
KW - tandem mass spectrometry
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246080
SN - 2227-9059
VL - 9
IS - 9
ER -
TY - JOUR
A1 - Dech, Stefan
A1 - Holzwarth, Stefanie
A1 - Asam, Sarah
A1 - Andresen, Thorsten
A1 - Bachmann, Martin
A1 - Boettcher, Martin
A1 - Dietz, Andreas
A1 - Eisfelder, Christina
A1 - Frey, Corinne
A1 - Gesell, Gerhard
A1 - Gessner, Ursula
A1 - Hirner, Andreas
A1 - Hofmann, Matthias
A1 - Kirches, Grit
A1 - Klein, Doris
A1 - Klein, Igor
A1 - Kraus, Tanja
A1 - Krause, Detmar
A1 - Plank, Simon
A1 - Popp, Thomas
A1 - Reinermann, Sophie
A1 - Reiners, Philipp
A1 - Roessler, Sebastian
A1 - Ruppert, Thomas
A1 - Scherbachenko, Alexander
A1 - Vignesh, Ranjitha
A1 - Wolfmueller, Meinhard
A1 - Zwenzner, Hendrik
A1 - Kuenzer, Claudia
T1 - Potential and challenges of harmonizing 40 years of AVHRR data: the TIMELINE experience
JF - Remote Sensing
N2 - Earth Observation satellite data allows for the monitoring of the surface of our planet at predefined intervals covering large areas. However, there is only one medium resolution sensor family in orbit that enables an observation time span of 40 and more years at a daily repeat interval. This is the AVHRR sensor family. If we want to investigate the long-term impacts of climate change on our environment, we can only do so based on data that remains available for several decades. If we then want to investigate processes with respect to climate change, we need very high temporal resolution enabling the generation of long-term time series and the derivation of related statistical parameters such as mean, variability, anomalies, and trends. The challenges to generating a well calibrated and harmonized 40-year-long time series based on AVHRR sensor data flown on 14 different platforms are enormous. However, only extremely thorough pre-processing and harmonization ensures that trends found in the data are real trends and not sensor-related (or other) artefacts. The generation of European-wide time series as a basis for the derivation of a multitude of parameters is therefore an extremely challenging task, the details of which are presented in this paper.
KW - AVHRR
KW - Earth Observation
KW - harmonization
KW - time series analysis
KW - climate related trends
KW - automatic processing
KW - Europe
KW - TIMELINE
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246134
SN - 2072-4292
VL - 13
IS - 18
ER -
TY - JOUR
A1 - Hennig, Thomas
A1 - Djakovic, Lara
A1 - Dölken, Lars
A1 - Whisnant, Adam W.
T1 - A Review of the Multipronged Attack of Herpes Simplex Virus 1 on the Host Transcriptional Machinery
JF - Viruses
N2 - During lytic infection, herpes simplex virus (HSV) 1 induces a rapid shutoff of host RNA synthesis while redirecting transcriptional machinery to viral genes. In addition to being a major human pathogen, there is burgeoning clinical interest in HSV as a vector in gene delivery and oncolytic therapies, necessitating research into transcriptional control. This review summarizes the array of impacts that HSV has on RNA Polymerase (Pol) II, which transcribes all mRNA in infected cells. We discuss alterations in Pol II holoenzymes, post-translational modifications, and how viral proteins regulate specific activities such as promoter-proximal pausing, splicing, histone repositioning, and termination with respect to host genes. Recent technological innovations that have reshaped our understanding of previous observations are summarized in detail, along with specific research directions and technical considerations for future studies.
KW - herpes simplex virus
KW - RNA polymerase II
KW - transcription
KW - host shutoff
KW - promoter-proximal pausing
KW - C-terminal domain
KW - polyadenylation
KW - splicing
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246165
SN - 1999-4915
VL - 13
IS - 9
ER -
TY - JOUR
A1 - Schroer, Guido
A1 - Toussaint, Valérie
A1 - Bachmann, Stephanie
A1 - Pöppler, Ann‐Christin
A1 - Gierlich, Christian Henning
A1 - Delidovich, Irina
T1 - Functional Phenylboronate Polymers for the Recovery of Diols, Sugar Alcohols, and Saccharides from Aqueous Solution
JF - ChemSusChem
N2 - The ongoing transition from fossil to renewable feedstocks demands new efficient processes for an economically viable production of biomass‐derived commodities and fine chemicals. Novel energy‐ and material‐efficient product purification and separation will play a crucial role due to altered product and feed composition. The present study comprises the synthesis and tests of cross‐linked p‐vinylphenylboronate polymers for the separation of 18 diols, sugar alcohols, and saccharides, which can be obtained during biomass processing. The separation was based on molecular recognition, that is, esterification of the phenylboronate with vicinal diols. A correlation of the molecular complexation constant, the polymer swelling, and the maximum adsorption capacity was found. The adsorption curves over time were recorded. Preliminary results on competitive adsorption of binary mixtures showed a high potential for the separation of substrates with significantly different complexation constants. Desorption tests implied easier desorption of substrates that only adsorb on the outer polymer shell.
KW - adsorption
KW - biomass
KW - phenylboronate
KW - polymers
KW - separation techniques
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239889
VL - 14
IS - 23
SP - 5207
EP - 5215
ER -
TY - JOUR
A1 - Shityakov, Sergey
A1 - Hayashi, Kentaro
A1 - Störk, Stefan
A1 - Scheper, Verena
A1 - Lenarz, Thomas
A1 - Förster, Carola Y.
T1 - The conspicuous link between ear, brain and heart − Could neurotrophin-treatment of age-related hearing loss help prevent Alzheimer's disease and associated amyloid cardiomyopathy?
JF - Biomolecules
N2 - Alzheimer's disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction and cognitive decline. While the deposition of amyloid β peptide (Aβ) and the formation of neurofibrillary tangles (NFTs) are the pathological hallmarks of AD-affected brains, the majority of cases exhibits a combination of comorbidities that ultimately lead to multi-organ failure. Of particular interest, it can be demonstrated that Aβ pathology is present in the hearts of patients with AD, while the formation of NFT in the auditory system can be detected much earlier than the onset of symptoms. Progressive hearing impairment may beget social isolation and accelerate cognitive decline and increase the risk of developing dementia. The current review discusses the concept of a brain–ear–heart axis by which Aβ and NFT inhibition could be achieved through targeted supplementation of neurotrophic factors to the cochlea and the brain. Such amyloid inhibition might also indirectly affect amyloid accumulation in the heart, thus reducing the risk of developing AD-associated amyloid cardiomyopathy and cardiovascular disease.
KW - Alzheimer's disease
KW - amyloid cardiomyopathy
KW - heart failure
KW - age-related hearing loss
KW - neurotrophins
KW - blood–brain barrier
KW - blood–labyrinth barrier
KW - spiral ganglion neuron
KW - BDNF
KW - GDNF
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241084
SN - 2218-273X
VL - 11
IS - 6
ER -
TY - JOUR
A1 - Weiß, Martin
A1 - Hein, Grit
A1 - Hewig, Johannes
T1 - Between joy and sympathy: Smiling and sad recipient faces increase prosocial behavior in the dictator game
JF - International Journal of Environmental Research and Public Health
N2 - In human interactions, the facial expression of a bargaining partner may contain relevant information that affects prosocial decisions. We were interested in whether facial expressions of the recipient in the dictator game influence dictators´ ehavior. To test this, we conducted an online study (n = 106) based on a modified version of a dictator game. The dictators allocated money between themselves and another person (recipient), who had no possibility to respond to the dictator.
Importantly, before the allocation decision, the dictator was presented with the facial expression of the recipient (angry, disgusted, sad, smiling, or neutral). The results showed that dictators sent more money to recipients with sad or smiling facial expressions and less to recipients with angry or disgusted facial expressions compared with a neutral facial expression. Moreover, based on the sequential analysis of the decision and the interaction partner in the preceding trial, we found that decision-making depends upon previous interactions.
KW - emotional influence
KW - dictator game
KW - facial expression
KW - social decision-making
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241106
VL - 18
IS - 11
ER -
TY - JOUR
A1 - Lilla, Nadine
A1 - Kessler, Almuth F.
A1 - Weiland, Judith
A1 - Ernestus, Ralf-Ingo
A1 - Westermaier, Thomas
T1 - Case Report: A Case Series Using Natural Anatomical Gaps — Posterior Cervical Approach to Skull Base and Upper Craniocervical Meningiomas Without Bone Removal
JF - Frontiers in Surgery
N2 - Background: Removal of anteriorly located tumors of the upper cervical spine and craniovertebral junction (CVJ) is a particular surgical challenge. Extensive approaches are associated with pain, restricted mobility of neck and head and, in case of foramen magnum and clivus tumors, with retraction of brainstem and cerebellum.
Methods: Four symptomatic patients underwent resection of anteriorly located upper cervical and lower clivus meningiomas without laminotomy or craniotomy using a minimally invasive posterior approach. Distances of natural gaps between C0/C1, C1/C2, and C2/C3 were measured using preoperative CT scans and intraoperative lateral x-rays.
Results: In all patients, safe and complete resection was conducted by the opening of the dura between C0/C1, C1/C2, and C2/C3, respectively. There were no surgical complications. Local pain was reported as very moderate by all patients and postoperative recovery was extremely fast. All tumors had a rather soft consistency, allowing mass reduction prior to removal of the tumor capsule and were well separable from lower cranial nerves and vascular structures.
Conclusion: If tumor consistency is appropriate for careful mass reduction before removal of the tumor capsule and if tumor margins are not firmly attached to crucial structures, then upper cervical, foramen magnum, and lower clivus meningiomas can be safely and completely removed through natural gaps in the CVJ region. Both prerequisites usually become clear early during surgery. Thus, this tumor entity may be planned using this minimally invasive approach and may be extended if tumor consistency turns out to be less unfavorable for resection or if crucial structures cannot be easily separated from the tumor.
KW - minimally invasive
KW - meningioma
KW - cervical spine
KW - spinal tumor operation
KW - craniovertebral junction
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244613
SN - 2296-875X
VL - 8
ER -
TY - JOUR
A1 - Dekant, Raphael
A1 - Langer, Michael
A1 - Lupp, Maria
A1 - Adaku Chilaka, Cynthia
A1 - Mally, Angela
T1 - In vitro and in vivo analysis of ochratoxin A-derived glucuronides and mercapturic acids as biomarkers of exposure
JF - Toxins
N2 - Ochratoxin A (OTA) is a widespread food contaminant, with exposure estimated to range from 0.64 to 17.79 ng/kg body weight (bw) for average consumers and from 2.40 to 51.69 ng/kg bw per day for high consumers. Current exposure estimates are, however, associated with considerable uncertainty. While biomarker-based approaches may contribute to improved exposure assessment, there is yet insufficient data on urinary metabolites of OTA and their relation to external dose to allow reliable estimates of daily intake. This study was designed to assess potential species differences in phase II biotransformation in vitro and to establish a correlation between urinary OTA-derived glucuronides and mercapturic acids and external exposure in rats in vivo. In vitro analyses of OTA metabolism using the liver S9 of rats, humans, rabbits and minipigs confirmed formation of an OTA glucuronide but provided no evidence for the formation of OTA-derived mercapturic acids to support their use as biomarkers. Similarly, OTA-derived mercapturic acids were not detected in urine of rats repeatedly dosed with OTA, while indirect analysis using enzymatic hydrolysis of the urine samples prior to LC–MS/MS established a linear relationship between urinary glucuronide excretion and OTA exposure. These results support OTA-derived glucuronides but not mercapturic acids as metabolites suitable for biomonitoring.
KW - ochratoxin A
KW - biomarker of exposure
KW - glucuronide
KW - mercapturic acid
KW - mycotoxin
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245146
SN - 2072-6651
VL - 13
IS - 8
ER -
TY - JOUR
A1 - Scheiner, Ricarda
A1 - Lim, Kayun
A1 - Meixner, Marina D.
A1 - Gabel, Martin S.
T1 - Comparing the appetitive learning performance of six European honeybee subspecies in a common apiary
JF - Insects
N2 - The Western honeybee (Apis mellifera L.) is one of the most widespread insects with numerous subspecies in its native range. How far adaptation to local habitats has affected the cognitive skills of the different subspecies is an intriguing question that we investigate in this study. Naturally mated queens of the following five subspecies from different parts of Europe were transferred to Southern Germany: A. m. iberiensis from Portugal, A. m. mellifera from Belgium, A. m. macedonica from Greece, A. m. ligustica from Italy, and A. m. ruttneri from Malta. We also included the local subspecies A. m. carnica in our study. New colonies were built up in a common apiary where the respective queens were introduced. Worker offspring from the different subspecies were compared in classical olfactory learning performance using the proboscis extension response. Prior to conditioning, we measured individual sucrose responsiveness to investigate whether possible differences in learning performances were due to differential responsiveness to the sugar water reward. Most subspecies did not differ in their appetitive learning performance. However, foragers of the Iberian honeybee, A. m. iberiensis, performed significantly more poorly, despite having a similar sucrose responsiveness. We discuss possible causes for the poor performance of the Iberian honeybees, which may have been shaped by adaptation to the local habitat.
KW - adaptation
KW - Apis mellifera
KW - olfactory learning
KW - proboscis extension response
KW - sucrose responsiveness
KW - genetic diversity
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245180
SN - 2075-4450
VL - 12
IS - 9
ER -
TY - JOUR
A1 - Lauruschkat, Chris D.
A1 - Etter, Sonja
A1 - Schnack, Elisabeth
A1 - Ebel, Frank
A1 - Schäuble, Sascha
A1 - Page, Lukas
A1 - Rümens, Dana
A1 - Dragan, Mariola
A1 - Schlegel, Nicolas
A1 - Panagiotou, Gianni
A1 - Kniemeyer, Olaf
A1 - Brakhage, Axel A.
A1 - Einsele, Hermann
A1 - Wurster, Sebastian
A1 - Loeffler, Juergen
T1 - Chronic occupational mold exposure drives expansion of Aspergillus-reactive type 1 and type 2 T-helper cell responses
JF - Journal of Fungi
N2 - Occupational mold exposure can lead to Aspergillus-associated allergic diseases including asthma and hypersensitivity pneumonitis. Elevated IL-17 levels or disbalanced T-helper (Th) cell expansion were previously linked to Aspergillus-associated allergic diseases, whereas alterations to the Th cell repertoire in healthy occupationally exposed subjects are scarcely studied. Therefore, we employed functional immunoassays to compare Th cell responses to A. fumigatus antigens in organic farmers, a cohort frequently exposed to environmental molds, and non-occupationally exposed controls. Organic farmers harbored significantly higher A. fumigatus-specific Th-cell frequencies than controls, with comparable expansion of Th1- and Th2-cell frequencies but only slightly elevated Th17-cell frequencies. Accordingly, Aspergillus antigen-induced Th1 and Th2 cytokine levels were strongly elevated, whereas induction of IL-17A was minimal. Additionally, increased levels of some innate immune cell-derived cytokines were found in samples from organic farmers. Antigen-induced cytokine release combined with Aspergillus-specific Th-cell frequencies resulted in high classification accuracy between organic farmers and controls. Aspf22, CatB, and CipC elicited the strongest differences in Th1 and Th2 responses between the two cohorts, suggesting these antigens as potential candidates for future bio-effect monitoring approaches. Overall, we found that occupationally exposed agricultural workers display a largely balanced co-expansion of Th1 and Th2 immunity with only minor changes in Th17 responses.
KW - mold exposure
KW - immunoassay
KW - biomarker
KW - Aspergillus
KW - cytokines
KW - inflammation
KW - adaptive immunity
KW - hypersensitivity
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245202
SN - 2309-608X
VL - 7
IS - 9
ER -
TY - JOUR
A1 - Opitz, Timm
A1 - Schuwerk, Tobias
A1 - Paulus, Markus
A1 - Kloo, Daniela
A1 - Osterhaus, Christopher
A1 - Lesch, Klaus‐Peter
A1 - Sodian, Beate
T1 - No links between genetic variation and developing theory of mind: A preregistered replication attempt of candidate gene studies
JF - Developmental Science
N2 - Genetic variability is being discussed as a source of inter‐individual differences in Theory of Mind development. Previous studies documented an association between variations in DRD4 VNTR 48 bp, OXTR rs53576, COMT rs4680, and Theory of Mind task performance. As empirical evidence on these associations is sparse, we conducted a preregistered replication attempt of a study reporting a link between DRD4 VNTR 48 bp and false belief understanding in 50‐month‐old children [Lackner, C., Sabbagh, M. A., Hallinan, E., Liu, X., & Holden, J. J. (2012). Developmental Science, 15(2), 272–280.]. Additionally, we attempted a replication of studies on the role of OXTR rs53576 and COMT rs4680 in Theory of Mind. In both replication attempts, we did not find any evidence for associations between the sampled genetic markers and Theory of Mind ability in a series of analyses. Extending the replication attempt of Lackner et al., we employed longitudinal data from several tasks and measurement points, which allowed us to run follow‐up robustness checks with more reliable scores. These extensive analyses corroborated our null finding. This comprehensive non‐replication is important to balance current research on genetic markers of Theory of Mind. In a combined evaluation of our own and previous studies, we point to substantial methodological issues that research on the genetic basis of Theory of Mind development faces. We conclude that these limitations currently prevent firm conclusions on genetic influences on Theory of Mind development.
KW - COMT
KW - DRD4
KW - false belief
KW - OXTR
KW - theory of mind
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238812
VL - 24
IS - 5
ER -
TY - JOUR
A1 - Lauerer, Elias
A1 - Tiedemann, Elena
A1 - Polak, Thomas
A1 - Simmenroth, Anne
T1 - Can smoking cessation be taught online? A prospective study comparing e-learning and role-playing in medical education
JF - International Journal of Medical Education
N2 - Objectives: We compared the effect of different didactic formats - e - learning and role-playing - on medical students' knowledge and counselling skills in smoking cessation training.
Methods: At a German medical school, 145 third-year students were randomly allocated to attend an online course with video examples or an attendance course with role-playing. Students were trained in smoking cessation counselling according to the 5A's (ask, advise, assess, assist, arrange) for approximately 90 minutes. Practical skills were measured in an objective structured clinical examination (OSCE) and represent the primary endpoint of this prospective comparative study. Additionally, changes in theoretic knowledge were assessed by pre - and post - interventional questionnaires and a final written exam.
Results: In the OSCE, overall scores were higher in the attendance group (Mdn=70.8 % vs. 62.8 %; U=119; p=.087, n=36), but a statistical advantage was only found in one single counselling sequence (“Assist”: Mdn=66.7 % vs. 51.4 %; p = .049) and the rating of the standardised patients (M=4.7 vs. 4.2 out of 5 points, t(27.836)=2.0, p=.028). Students’ results (n=130) from self-assessment and written exams suggest that both approaches are equally well suited to increase theoretical knowledge. The online course was more time efficient (90 vs. 73 minutes).
Conclusions: Seminar and web-based training seem equally well suited for transferring knowledge and skills on tobacco cessation counselling. Considering their particular strengths, these two teaching approaches could be combined.
KW - medical education
KW - e-learning
KW - smoking cessation
KW - objective structured clinical examination
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230056
VL - 12
ER -
TY - JOUR
A1 - Anton, Sylvia
A1 - Rössler, Wolfgang
T1 - Plasticity and modulation of olfactory circuits in insects
JF - Cell and Tissue Research
N2 - Olfactory circuits change structurally and physiologically during development and adult life. This allows insects to respond to olfactory cues in an appropriate and adaptive way according to their physiological and behavioral state, and to adapt to their specific abiotic and biotic natural environment. We highlight here findings on olfactory plasticity and modulation in various model and non-model insects with an emphasis on moths and social Hymenoptera. Different categories of plasticity occur in the olfactory systems of insects. One type relates to the reproductive or feeding state, as well as to adult age. Another type of plasticity is context-dependent and includes influences of the immediate sensory and abiotic environment, but also environmental conditions during postembryonic development, periods of adult behavioral maturation, and short- and long-term sensory experience. Finally, plasticity in olfactory circuits is linked to associative learning and memory formation. The vast majority of the available literature summarized here deals with plasticity in primary and secondary olfactory brain centers, but also peripheral modulation is treated. The described molecular, physiological, and structural neuronal changes occur under the influence of neuromodulators such as biogenic amines, neuropeptides, and hormones, but the mechanisms through which they act are only beginning to be analyzed.
KW - antenna
KW - antennal lobe
KW - mushroom body
KW - neuromodulation
KW - structural synaptic plasticity
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235820
SN - 0302-766X
VL - 383
ER -
TY - JOUR
A1 - Freimann, A.
A1 - Dierkes, M.
A1 - Petermann, T.
A1 - Liman, C.
A1 - Kempf, F.
A1 - Schilling, K.
T1 - ESTNeT: a discrete event simulator for space-terrestrial networks
JF - CEAS Space Journal
N2 - The capabilities of small satellites have improved significantly in recent years. Specifically multi-satellite systems become increasingly popular, since they allow the support of new applications. The development and testing of these multi-satellite systems is a new challenge for engineers and requires the implementation of appropriate development and testing environments. In this paper, a modular network simulation framework for space–terrestrial systems is presented. It enables discrete event simulations for the development and testing of communication protocols, as well as mission-based analysis of other satellite system aspects, such as power supply and attitude control. ESTNeT is based on the discrete event simulator OMNeT++ and will be released under an open source license.
KW - space–terrestrial networks
KW - wireless communication
KW - system simulation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235835
SN - 1868-2502
VL - 13
ER -
TY - JOUR
A1 - Strzalkowska, A.
A1 - Strzalkowski, P.
A1 - Al Yousef, Y.
A1 - Grehn, F.
A1 - Hillenkamp, J.
A1 - Loewen, Nils A.
T1 - Exact matching of trabectome-mediated ab interno trabeculectomy to conventional trabeculectomy with mitomycin C followed for 2 years
JF - Graefe's Archive for Clinical and Experimental Ophthalmology
N2 - Purpose
We used exact matching for a highly balanced comparison of ab interno trabeculectomy (AIT) with the trabectome to trabeculectomy with mitomycin C (TRAB).
Methods
A total of 5485 patients who underwent AIT were exact-matched to 196 TRAB patients by baseline intraocular pressure (IOP), number of glaucoma medications, and glaucoma type. Nearest-neighbor–matching was applied to age. Success was defined as a final IOP of less than 21 mmHg, IOP reduction of at least 20% reduction from baseline, and no secondary surgical interventions. Outcomes were measured at 1, 3, 6, 12, 18, and 24 months.
Results
A total of 165 AIT could be matched to 165 TRAB. The mean baseline IOP was 22.3 ± 5.6 mmHg, and the baseline number of glaucoma medications was 2.7 ± 1.1 in both groups. At 24 months, IOP was reduced to 15.8 ± 5.2 mmHg in AIT and 12.4 ± 4.7 mmHg in TRAB. IOP was lower than baseline at all visits (p < 0.01) and lower in TRAB than AIT (p < 0.01). Glaucoma medications were reduced to 2.1 ± 1.3 in AIT and 0.2 ± 0.8 in TRAB. Compared to baseline, patients used fewer drops postoperatively (p < 0.01) and more infrequently in TRAB than in AIT (p > 0.01). Secondary surgical interventions had the highest impact on success and became necessary in 15 AIT and 59 TRAB patients. Thirty-two challenging events occurred in TRAB and none in AIT.
Conclusion
Both AIT and TRAB reduced IOP and medications. This reduction was more significant in TRAB but at the expense of four times as many secondary interventions.
KW - trabeculectomy
KW - Ab interno trabeculectomy
KW - trabectome
KW - exact matching
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235224
SN - 0721-832X
VL - 259
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
A1 - Buck, Andreas K.
A1 - Hartrampf, Philipp E.
A1 - Serfling, Sebastian E.
A1 - Scheurlen, Michael
A1 - Wester, Hans-Jürgen
A1 - Meining, Alexander
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Kircher, Malte
T1 - CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
JF - Diagnostics
N2 - We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
KW - CXCR4
KW - NET
KW - NEC
KW - 68Ga-Pentixafor
KW - 18F-FDG
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234231
SN - 2075-4418
VL - 11
IS - 4
ER -
TY - JOUR
A1 - Bachmann, Friederike
A1 - Schreder, Martin
A1 - Engelhardt, Monika
A1 - Langer, Christian
A1 - Wolleschak, Denise
A1 - Mügge, Lars Olof
A1 - Dürk, Heinz
A1 - Schäfer-Eckart, Kerstin
A1 - Blau, Igor Wolfgang
A1 - Gramatzki, Martin
A1 - Liebisch, Peter
A1 - Grube, Matthias
A1 - Metzler, Ivana v.
A1 - Bassermann, Florian
A1 - Metzner, Bernd
A1 - Röllig, Christoph
A1 - Hertenstein, Bernd
A1 - Khandanpour, Cyrus
A1 - Dechow, Tobias
A1 - Hebart, Holger
A1 - Jung, Wolfram
A1 - Theurich, Sebastian
A1 - Maschmeyer, Georg
A1 - Salwender, Hans
A1 - Hess, Georg
A1 - Bittrich, Max
A1 - Rasche, Leo
A1 - Brioli, Annamaria
A1 - Eckardt, Kai-Uwe
A1 - Straka, Christian
A1 - Held, Swantje
A1 - Einsele, Hermann
A1 - Knop, Stefan
T1 - Kinetics of renal function during induction in newly diagnosed multiple myeloma: results of two prospective studies by the German Myeloma Study Group DSMM
JF - Cancers
N2 - Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.
KW - multiple myeloma
KW - renal failure
KW - kidney
KW - bortezomib
KW - lenalidomide
KW - induction regimen
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234139
SN - 2072-6694
VL - 13
IS - 6
ER -
TY - JOUR
A1 - Egenolf, Nadine
A1 - Altenschildesche, Caren Meyer zu
A1 - Kreß, Luisa
A1 - Eggermann, Katja
A1 - Namer, Barbara
A1 - Gross, Franziska
A1 - Klitsch, Alexander
A1 - Malzacher, Tobias
A1 - Kampik, Daniel
A1 - Malik, Rayaz A.
A1 - Kurth, Ingo
A1 - Sommer, Claudia
A1 - Üçeyler, Nurcan
T1 - Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study
JF - Therapeutic Advances in Neurological Disorders
N2 - Background and aims:
Small fiber neuropathy (SFN) is increasingly suspected in patients with pain of uncertain origin, and making the diagnosis remains a challenge lacking a diagnostic gold standard.
Methods:
In this case–control study, we prospectively recruited 86 patients with a medical history and clinical phenotype suggestive of SFN. Patients underwent neurological examination, quantitative sensory testing (QST), and distal and proximal skin punch biopsy, and were tested for pain-associated gene loci. Fifty-five of these patients additionally underwent pain-related evoked potentials (PREP), corneal confocal microscopy (CCM), and a quantitative sudomotor axon reflex test (QSART).
Results:
Abnormal distal intraepidermal nerve fiber density (IENFD) (60/86, 70%) and neurological examination (53/86, 62%) most frequently reflected small fiber disease. Adding CCM and/or PREP further increased the number of patients with small fiber impairment to 47/55 (85%). Genetic testing revealed potentially pathogenic gene variants in 14/86 (16%) index patients. QST, QSART, and proximal IENFD were of lower impact.
Conclusion:
We propose to diagnose SFN primarily based on the results of neurological examination and distal IENFD, with more detailed phenotyping in specialized centers.
KW - algorithm
KW - diagnosis
KW - neurological examination
KW - skin punch biopsy
KW - small fiber neuropathy
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232019
SN - 1756-2864
VL - 14
ER -
TY - JOUR
A1 - Kunz, Felix
A1 - Hirth, Matthias
A1 - Schweitzer, Tilmann
A1 - Linz, Christian
A1 - Goetz, Bernhard
A1 - Stellzig-Eisenhauer, Angelika
A1 - Borchert, Kathrin
A1 - Böhm, Hartmut
T1 - Subjective perception of craniofacial growth asymmetries in patients with deformational plagiocephaly
JF - Clinical Oral Investigations
N2 - Objectives
The present investigation aimed to evaluate the subjective perception of deformational cranial asymmetries by different observer groups and to compare these subjective perceptions with objective parameters.
Materials and methods
The 3D datasets of ten infants with different severities of deformational plagiocephaly (DP) were presented to 203 observers, who had been subdivided into five different groups (specialists, pediatricians, medical doctors (not pediatricians), parents of infants with DP, and laypersons). The observers rated their subjective perception of the infants’ cranial asymmetries using a 4-point Likert-type scale. The ratings from the observer groups were compared with one another using a multilevel modelling linear regression analysis and were correlated with four commonly used parameters to objectively quantify the cranial asymmetries.
Results
No significant differences were found between the ratings of the specialists and those of the parents of infants with DP, but both groups provided significantly more asymmetric ratings than did pediatricians, medical doctors, or laypersons. Moreover, the subjective perception of cranial asymmetries correlated significantly with commonly used parameters for objectively quantifying cranial asymmetries.
Conclusions
Our results demonstrate that different observer groups perceive the severity of cranial asymmetries differently. Pediatricians’ more moderate perception of cranial asymmetries may reduce the likelihood of parents to seek therapeutic interventions for their infants. Moreover, we identified some objective symmetry-related parameters that correlated strongly with the observers’ subjective perceptions.
Clinical relevance
Knowledge about these findings is important for clinicians when educating parents of infants with DP about the deformity.
KW - infants with deformational plagiocephaly (DP)
KW - deformational cranial asymmetry
KW - subjective perception
KW - positionalskull deformities
KW - three-dimensional
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232803
SN - 1432-6981
VL - 25
ER -
TY - JOUR
A1 - Merz, Viktor
A1 - Merz, Julia
A1 - Kirchner, Maximilian
A1 - Lenhart, Julian
A1 - Marder, Todd B.
A1 - Krueger, Anke
T1 - Pyrene-Based "Turn-Off" Probe with Broad Detection Range for Cu\(^{2+}\), Pb\(^{2+}\) and Hg\(^{2+}\) Ions
JF - Chemistry—A European Journal
N2 - Detection of metals in different environments with high selectivity and specificity is one of the prerequisites of the fight against environmental pollution with these elements. Pyrenes are well suited for the fluorescence sensing in different media. The applied sensing principle typically relies on the formation of intra- and intermolecular excimers, which is however limiting the sensitivity range due to masking of e. g. quenching effects by the excimer emission. Herein we report a highly selective, structurally rigid chemical sensor based on the monomer fluorescence of pyrene moieties bearing triazole groups. This sensor can quantitatively detect Cu\(^{2+}\), Pb\(^{2+}\) and Hg\(^{2+}\) in organic solvents over a broad concentrations range, even in the presence of ubiquitous ions such as Na\(^{+}\), K\(^{+}\), Ca\(^{2+}\) and Mg\(^{2+}\). The strongly emissive sensor's fluorescence with a long lifetime of 165 ns is quenched by a 1 : 1 complex formation upon addition of metal ions in acetonitrile. Upon addition of a tenfold excess of the metal ion to the sensor, agglomerates with a diameter of about 3 nm are formed. Due to complex interactions in the system, conventional linear correlations are not observed for all concentrations. Therefore, a critical comparison between the conventional Job plot interpretation, the method of Benesi-Hildebrand, and a non-linear fit is presented. The reported system enables the specific and robust sensing of medically and environmentally relevant ions in the health-relevant nM range and could be used e. g. for the monitoring of the respective ions in waste streams.
KW - probes
KW - fluorescence spectroscopy
KW - pyrene
KW - heavy metals
KW - luminescence
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256803
VL - 27
IS - 31
ER -
TY - JOUR
A1 - Ankenbrand, Markus Johannes
A1 - Lohr, David
A1 - Schlötelburg, Wiebke
A1 - Reiter, Theresa
A1 - Wech, Tobias
A1 - Schreiber, Laura Maria
T1 - Deep learning-based cardiac cine segmentation: Transfer learning application to 7T ultrahigh-field MRI
JF - Magnetic Resonance in Medicine
N2 - Purpose
Artificial neural networks show promising performance in automatic segmentation of cardiac MRI. However, training requires large amounts of annotated data and generalization to different vendors, field strengths, sequence parameters, and pathologies is limited. Transfer learning addresses this challenge, but specific recommendations regarding type and amount of data required is lacking. In this study, we assess data requirements for transfer learning to experimental cardiac MRI at 7T where the segmentation task can be challenging. In addition, we provide guidelines, tools, and annotated data to enable transfer learning approaches by other researchers and clinicians.
Methods
A publicly available segmentation model was used to annotate a publicly available data set. This labeled data set was subsequently used to train a neural network for segmentation of left ventricle and myocardium in cardiac cine MRI. The network is used as starting point for transfer learning to 7T cine data of healthy volunteers (n = 22; 7873 images) by updating the pre-trained weights. Structured and random data subsets of different sizes were used to systematically assess data requirements for successful transfer learning.
Results
Inconsistencies in the publically available data set were corrected, labels created, and a neural network trained. On 7T cardiac cine images the model pre-trained on public imaging data, acquired at 1.5T and 3T, achieved DICE\(_{LV}\) = 0.835 and DICE\(_{MY}\) = 0.670. Transfer learning using 7T cine data and ImageNet weight initialization improved model performance to DICE\(_{LV}\) = 0.900 and DICE\(_{MY}\) = 0.791. Using only end-systolic and end-diastolic images reduced training data by 90%, with no negative impact on segmentation performance (DICE\(_{LV}\) = 0.908, DICE\(_{MY}\) = 0.805).
Conclusions
This work demonstrates and quantifies the benefits of transfer learning for cardiac cine image segmentation. We provide practical guidelines for researchers planning transfer learning projects in cardiac MRI and make data, models, and code publicly available.
KW - 7T
KW - ultrahigh-field
KW - transfer learning
KW - segmentation
KW - neural networks
KW - deep learning
KW - cardiac magnetic resonance
KW - cardiac function
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257604
VL - 86
IS - 4
ER -
TY - JOUR
A1 - Morais, António P.
A1 - Pasechnik, Roman
A1 - Porod, Werner
T1 - Grand Unified origin of gauge interactions and families replication in the Standard Model
JF - Universe
N2 - The tremendous phenomenological success of the Standard Model (SM) suggests that its flavor structure and gauge interactions may not be arbitrary but should have a fundamental first-principle explanation. In this work, we explore how the basic distinctive properties of the SM dynamically emerge from a unified New Physics framework tying together both flavor physics and Grand Unified Theory (GUT) concepts. This framework is suggested by a novel anomaly-free supersymmetric chiral E\(_6\)×SU(2)\(_F\)×U(1)\(_F\) GUT containing the SM. Among the most appealing emergent properties of this theory is the Higgs-matter unification with a highly-constrained massless chiral sector featuring two universal Yukawa couplings close to the GUT scale. At the electroweak scale, the minimal SM-like effective field theory limit of this GUT represents a specific flavored three-Higgs doublet model consistent with the observed large hierarchies in the quark mass spectra and mixing already at tree level.
KW - grand unified theories
KW - supersymmetry
KW - phenomenology of New Physics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250237
SN - 2218-1997
VL - 7
IS - 12
ER -
TY - JOUR
A1 - Wagenbrenner, Mike
A1 - Mayer-Wagner, Susanne
A1 - Rudert, Maximilian
A1 - Holzapfel, Boris Michael
A1 - Weissenberger, Manuel
T1 - Combinations of hydrogels and mesenchymal stromal cells (MSCs) for cartilage tissue engineering — a review of the literature
JF - Gels
N2 - Cartilage offers limited regenerative capacity. Cell-based approaches have emerged as a promising alternative in the treatment of cartilage defects and osteoarthritis. Due to their easy accessibility, abundancy, and chondrogenic potential mesenchymal stromal cells (MSCs) offer an attractive cell source. MSCs are often combined with natural or synthetic hydrogels providing tunable biocompatibility, biodegradability, and enhanced cell functionality. In this review, we focused on the different advantages and disadvantages of various natural, synthetic, and modified hydrogels. We examined the different combinations of MSC-subpopulations and hydrogels used for cartilage engineering in preclinical and clinical studies and reviewed the effects of added growth factors or gene transfer on chondrogenesis in MSC-laden hydrogels. The aim of this review is to add to the understanding of the disadvantages and advantages of various combinations of MSC-subpopulations, growth factors, gene transfers, and hydrogels in cartilage engineering.
KW - hydrogels
KW - osteoarthritis
KW - cartilage defects
KW - MSCs
KW - cartilage regeneration
KW - tissue engineering
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250177
SN - 2310-2861
VL - 7
IS - 4
ER -
TY - JOUR
A1 - Hoche, Joscha
A1 - Flock, Marco
A1 - Miao, Xincheng
A1 - Philipp, Luca Nils
A1 - Wenzel, Michael
A1 - Fischer, Ingo
A1 - Mitric, Roland
T1 - Excimer formation dynamics in the isolated tetracene dimer
JF - Chemical Science
N2 - The understanding of excimer formation and its interplay with the singlet-correlated triplet pair state \(^{1}\)(TT) is of high significance for the development of efficient organic electronics. Here, we study the photoinduced dynamics of the tetracene dimer in the gas phase by time-resolved photoionisation and photoion imaging experiments as well as nonadiabatic dynamics simulations in order to obtain mechanistic insight into the excimer formation dynamics. The experiments are performed using a picosecond laser system for excitation into the S\(_{2}\) state and reveal a biexponential time dependence. The time constants, obtained as a function of excess energy, lie in the range between ≈10 ps and 100 ps and are assigned to the relaxation of the excimer on the S\(_{1}\) surface and to its deactivation to the ground state. Simulations of the quantum-classical photodynamics are carried out in the frame of the semi-empirical CISD and TD-lc-DFTB methods. Both theoretical approaches reveal a dominating relaxation pathway that is characterised by the formation of a perfectly stacked excimer. TD-lc-DFTB simulations have also uncovered a second relaxation channel into a less stable dimer conformation in the S\(_{1}\) state. Both methods have consistently shown that the electronic and geometric relaxation to the excimer state is completed in less than 10 ps. The inclusion of doubly excited states in the CISD dynamics and their diabatisation further allowed to observe a transient population of the \(^{1}\)(TT) state, which, however, gets depopulated on a timescale of 8 ps, leading finally to the trapping in the excimer minimum.
KW - excimer formation
KW - tetracene dimer
KW - organic electronics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-251559
VL - 12
IS - 36
SP - 11965
EP - 11975
ER -
TY - JOUR
A1 - Strekalova, Tatyana
A1 - Veniaminova, Ekaterina
A1 - Svirin, Evgeniy
A1 - Kopeikina, Ekaterina
A1 - Veremeyko, Tatyana
A1 - Yung, Amanda W. Y.
A1 - Proshin, Andrey
A1 - Tan, Shawn Zheng Kai
A1 - Khairuddin, Sharafuddin
A1 - Lim, Lee Wei
A1 - Lesch, Klaus-Peter
A1 - Walitza, Susanne
A1 - Anthony, Daniel C.
A1 - Ponomarev, Eugene D.
T1 - Sex-specific ADHD-like behaviour, altered metabolic functions, and altered EEG activity in sialyltransferase ST3GAL5-deficient mice
JF - Biomolecules
N2 - A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5\(^{−/−}\)) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5\(^{−/−}\) mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5\(^{−/−}\) mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5\(^{−/−}\) mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5\(^{−/−}\) mice. Together, St3gal5\(^{−/−}\) mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.
KW - lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5)
KW - attention-deficit/hyperactivity disorder (ADHD)
KW - insulin receptor (IR)
KW - sex differences
KW - electroencephalogram (EEG)
KW - mice
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250071
SN - 2218-273X
VL - 11
IS - 12
ER -
TY - JOUR
A1 - Fuss, Carmina Teresa
A1 - Other, Katharina
A1 - Heinze, Britta
A1 - Landwehr, Laura-Sophie
A1 - Wiegering, Armin
A1 - Kalogirou, Charis
A1 - Hahner, Stefanie
A1 - Fassnacht, Martin
T1 - Expression of the chemokine receptor CCR7 in the normal adrenal gland and adrenal tumors and its correlation with clinical outcome in adrenocortical carcinoma
JF - Cancers
N2 - Background: The chemokine receptor CCR7 is crucial for an intact immune function, but its expression is also associated with clinical outcome in several malignancies. No data exist on the expression of CCR7 in adrenocortical tumors. Methods: CCR7 expression was investigated by qRT-PCR and immunohistochemistry in 4 normal adrenal glands, 59 adrenocortical adenomas, and 181 adrenocortical carcinoma (ACC) samples. Results: CCR7 is highly expressed in the outer adrenocortical zones and medulla. Aldosterone-producing adenomas showed lower CCR7 protein levels (H-score 1.3 ± 1.0) compared to non-functioning (2.4 ± 0.5) and cortisol-producing adenomas (2.3 ± 0.6), whereas protein expression was variable in ACC (1.8 ± 0.8). In ACC, CCR7 protein expression was significantly higher in lymph node metastases (2.5 ± 0.5) compared to primary tumors (1.8±0.8) or distant metastases (2.0 ± 0.4; p < 0.01). mRNA levels of CCR7 were not significantly different between ACCs, normal adrenals, and adrenocortical adenomas. In contrast to other tumor entities, neither CCR7 protein nor mRNA expression significantly impacted patients' survival. Conclusion: We show that CCR7 is expressed on mRNA and protein level across normal adrenals, benign adrenocortical tumors, as well as ACCs. Given that CCR7 did not influence survival in ACC, it is probably not involved in tumor progression, but it could play a role in adrenocortical homeostasis.
KW - CCR7
KW - chemokine receptor
KW - adrenocortical carcinoma
KW - adrenal tumors
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250112
SN - 2072-6694
VL - 13
IS - 22
ER -
TY - JOUR
A1 - Kölligan, Daniel
T1 - Murmur, heat and bonds – on some words of magic and healing
JF - Indogermanische Forschungen
N2 - The paper argues that a) Germanic *tauf/ƀra- (Germ. Zauber, etc.) is related to a root PIE *deu̯p- ‘beat; make a hollow sound, resound’ found in Greek δοῦπος ‘thud’, etc., b) Greek φάρμακον goes back to the root PIE *gʷʰer- ‘heat’ (Gk. θερμός, etc.) implying healing by fomentation, and c) Armenian hiwand ‘sick’, borrowed from Iranian, to PIE *sh₂ei̯- ‘bind’ relying on the notion of disease as a supernatural bond.
KW - magic
KW - spell
KW - healing
KW - disease
KW - lexicon
KW - etymology
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250976
SN - 1613-0405
SN - 0019-7262
N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL - 126
IS - 1
SP - 107
EP - 134
ER -
TY - JOUR
A1 - Kölligan, Daniel
T1 - A note on Vedic cīti-
JF - Indogermanische Forschungen
N2 - Vedic cīti-, attested in the Atharvaveda, is argued to be related to Av. ṣ̌āitī-, OP šiyāti- ‘happiness’ built to PIE *kʷi̯eh₁- ‘to (come to) rest’.
KW - Vedic
KW - Atharvaveda
KW - disease
KW - healing
KW - etymology
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250986
SN - 1613-0405
SN - 0019-7262
N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL - 126
IS - 1
SP - 135
EP - 140
ER -
TY - JOUR
A1 - Tamihardja, Jörg
A1 - Lutyj, Paul
A1 - Kraft, Johannes
A1 - Lisowski, Dominik
A1 - Weick, Stefan
A1 - Flentje, Michael
A1 - Polat, Bülent
T1 - Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis
JF - Frontiers in Oncology
N2 - Purpose
Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer.
Methods
338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition.
Results
Median follow-up was 101.8 months. 15 (4.4%)/115 (34.0%)/208 (61.5%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7% and 75.9% for all patients. The estimated 5-year bRFS was 93.3%, 93.4% and 79.5% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5% and 70.0%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3% and 5.0% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6%/0.3%.
Conclusions
Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.
KW - prostate cancer
KW - high-dose-rate (HDR) brachytherapy
KW - radiotherapy
KW - long-term outcome
KW - toxicity
KW - external beam radiotherapy (EBRT)
KW - biochemical relapse free survival
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250992
SN - 2234-943X
VL - 11
ER -
TY - JOUR
A1 - Strilciuc, Stefan
A1 - Vécsei, László
A1 - Boering, Dana
A1 - Pražnikar, Aleš
A1 - Kaut, Oliver
A1 - Riederer, Peter
A1 - Battistin, Leontino
T1 - Safety of Cerebrolysin for neurorecovery after acute ischemic stroke: a systematic review and meta-analysis of twelve randomized-controlled trials
JF - Pharmaceuticals
N2 - We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed, and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis were conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p > 0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.
KW - ischemic stroke
KW - safety
KW - Cerebrolysin
KW - neurorehabilitation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252403
SN - 1424-8247
VL - 14
IS - 12
ER -
TY - JOUR
A1 - Nguemeni, Carine
A1 - Hiew, Shawn
A1 - Kögler, Stefanie
A1 - Homola, György A.
A1 - Volkmann, Jens
A1 - Zeller, Daniel
T1 - Split-belt training but not cerebellar anodal tDCS improves stability control and reduces risk of fall in patients with multiple sclerosis
JF - Brain Sciences
N2 - The objective of this study was to examine the therapeutic potential of multiple sessions of training on a split-belt treadmill (SBT) combined with cerebellar anodal transcranial direct current stimulation (tDCS) on gait and balance in People with Multiple Sclerosis (PwMS). Twenty-two PwMS received six sessions of anodal (PwMS\(_{real}\), n = 12) or sham (PwMS\(_{sham}\), n = 10) tDCS to the cerebellum prior to performing the locomotor adaptation task on the SBT. To evaluate the effect of the intervention, functional gait assessment (FGA) scores and distance walked in 2 min (2MWT) were measured at the baseline (T0), day 6 (T5), and at the 4-week follow up (T6). Locomotor performance and changes of motor outcomes were similar in PwMS\(_{real}\) and PwMS\(_{sham}\) independently from tDCS mode applied to the cerebellum (anodal vs. sham, on FGA, p = 0.23; and 2MWT, p = 0.49). When the data were pooled across the groups to investigate the effects of multiple sessions of SBT training alone, significant improvement of gait and balance was found on T5 and T6, respectively, relative to baseline (FGA, p < 0.001 for both time points). The FGA change at T6 was significantly higher than at T5 (p = 0.01) underlining a long-lasting improvement. An improvement of the distance walked during the 2MWT was also observed on T5 and T6 relative to T0 (p = 0.002). Multiple sessions of SBT training resulted in a lasting improvement of gait stability and endurance, thus potentially reducing the risk of fall as measured by FGA and 2MWT. Application of cerebellar tDCS during SBT walking had no additional effect on locomotor outcomes.
KW - multiple sclerosis
KW - split-belt treadmill
KW - cerebellar tDCS
KW - gait
KW - balance
KW - risk of fall
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252179
SN - 2076-3425
VL - 12
IS - 1
ER -
TY - JOUR
A1 - Khare, Siddhartha
A1 - Deslauriers, Annie
A1 - Morin, Hubert
A1 - Latifi, Hooman
A1 - Rossi, Sergio
T1 - Comparing time-lapse PhenoCams with satellite observations across the boreal forest of Quebec, Canada
JF - Remote Sensing
N2 - Intercomparison of satellite-derived vegetation phenology is scarce in remote locations because of the limited coverage area and low temporal resolution of field observations. By their reliable near-ground observations and high-frequency data collection, PhenoCams can be a robust tool for intercomparison of land surface phenology derived from satellites. This study aims to investigate the transition dates of black spruce (Picea mariana (Mill.) B.S.P.) phenology by comparing fortnightly the MODIS normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI) extracted using the Google Earth Engine (GEE) platform with the daily PhenoCam-based green chromatic coordinate (GCC) index. Data were collected from 2016 to 2019 by PhenoCams installed in six mature stands along a latitudinal gradient of the boreal forests of Quebec, Canada. All time series were fitted by double-logistic functions, and the estimated parameters were compared between NDVI, EVI, and GCC. The onset of GCC occurred in the second week of May, whereas the ending of GCC occurred in the last week of September. We demonstrated that GCC was more correlated with EVI (R\(^2\) from 0.66 to 0.85) than NDVI (R\(^2\) from 0.52 to 0.68). In addition, the onset and ending of phenology were shown to differ by 3.5 and 5.4 days between EVI and GCC, respectively. Larger differences were detected between NDVI and GCC, 17.05 and 26.89 days for the onset and ending, respectively. EVI showed better estimations of the phenological dates than NDVI. This better performance is explained by the higher spectral sensitivity of EVI for multiple canopy leaf layers due to the presence of an additional blue band and an optimized soil factor value. Our study demonstrates that the phenological observations derived from PhenoCam are comparable with the EVI index. We conclude that EVI is more suitable than NDVI to assess phenology in evergreen species of the northern boreal region, where PhenoCam data are not available. The EVI index could be used as a reliable proxy of GCC for monitoring evergreen species phenology in areas with reduced access, or where repeated data collection from remote areas are logistically difficult due to the extreme weather.
KW - PhenoCam
KW - GCC
KW - NDVI
KW - EVI
KW - Google Earth Engine
KW - coniferous species
KW - Picea mariana
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252213
SN - 2072-4292
VL - 14
IS - 1
ER -
TY - JOUR
A1 - Dosoo, Korshi
T1 - Healing traditions in Coptic magical texts
JF - Trends in Classics
N2 - Within the ‘market of healing’ of Christian Egypt (here broadly considered as the fourth through twelfth centuries CE), ‘magical’ practitioners represent an elusive yet recurrent category. This article explores the evidence for magical healing from three perspectives – first, literary texts which situate ‘magicians’ in competition with medical and ecclesiastical healing; second, the papyrological evidence of Coptic-language magical texts, which provide evidence for concepts of disease, wellness, and their mediation; and finally confronting the question of how these healing traditions might be understood within the methodologically materialistic framework of academic history, using the concepts of placebo and healing as a performance.
KW - Placebo
KW - healing
KW - Coptic
KW - magic
KW - ritual
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-251219
SN - 1866-7473
SN - 1866-7481
N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL - 13
IS - 1
SP - 44
EP - 94
ER -
TY - JOUR
A1 - Schmidt, Karsten
A1 - Jakubietz, Michael Georg
A1 - Gilbert, Fabian
A1 - Fenwick, Annabel
A1 - Meffert, Reiner Heribert
A1 - Jakubietz, Rafael Gregor
T1 - Muscle cuff in distal pedicled adipofascial sural artery flaps: a retrospective case control study
JF - PRS Global Open
N2 - Background:
Amputation after open tibial fracture occurs in 3% of cases. The rate increases when flap reconstruction is required. The standard care involves microsurgical tissue transfer although the pedicled reverse sural artery adipofascial flap (PRSAF) is a local alternative in patients endangered by a prolonged operative time. Incorporation of a gastrocnemius muscle cuff in this flap can be used to fill dead space and increase healing potential. Literature shows superior survival rates for both PRSAF and inclusion of a muscle cuff in comparison with the cutaneous version. The aim of the study was to compare the outcome of the PRSAF and the musculoadipofascial version (PRSMAF). We hypothesize that the PRSMAF provides similar lap viability and flap-related complication rates as does the adipofascial version. The muscle component may reduce the long-term osteomyelitis rate.
Methods:
Patients were evaluated retrospectively after reconstruction with either PRSAF or PRSMAF. Preoperative osteomyelitis, flap survival, complications and osteomyelitis clearance were analyzed.
Results:
The study shows preliminary results supporting the potential use of the PRSMAF. We compare either 23 PRSMAF or 20 PRSAF flaps. We found no statistically significant differences in flap survival or in complication rate.
Conclusions:
Although the anatomical situation may sometimes dictate the use of a free flap, a technically less-complicated option may in some cases offer a viable alternative. This study shows that the PRSMAF can serve as an alternative for complex bone defects in the limb, though it does not provide statistical improvement to the PRSAF.
KW - muscle cuff
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259875
VL - 9
IS - 3
ER -
TY - JOUR
A1 - Hojsgaard, Diego
A1 - Schartl, Manfred
T1 - Skipping sex: A nonrecombinant genomic assemblage of complementary reproductive modules
JF - BioEssays
N2 - The unusual occurrence and developmental diversity of asexual eukaryotes remain a puzzle. De novo formation of a functioning asexual genome requires a unique assembly of sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and to affect discrete components of sexuality and produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, that is, a nonrecombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.
KW - amphimixis
KW - apomixis
KW - automixis
KW - gynogenesis
KW - hybridogenesis
KW - parthenogenesis
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225818
VL - 43
IS - 1
ER -
TY - JOUR
A1 - Bousquet, Jean
A1 - Anto, Josep M.
A1 - Bachert, Claus
A1 - Haahtela, Tari
A1 - Zuberbier, Torsten
A1 - Czarlewski, Wienczyslawa
A1 - Bedbrook, Anna
A1 - Bosnic‐Anticevich, Sinthia
A1 - Walter Canonica, G.
A1 - Cardona, Victoria
A1 - Costa, Elisio
A1 - Cruz, Alvaro A.
A1 - Erhola, Marina
A1 - Fokkens, Wytske J.
A1 - Fonseca, Joao A.
A1 - Illario, Maddalena
A1 - Ivancevich, Juan‐Carlos
A1 - Jutel, Marek
A1 - Klimek, Ludger
A1 - Kuna, Piotr
A1 - Kvedariene, Violeta
A1 - Le, LTT
A1 - Larenas‐Linnemann, Désirée E.
A1 - Laune, Daniel
A1 - Lourenço, Olga M.
A1 - Melén, Erik
A1 - Mullol, Joaquim
A1 - Niedoszytko, Marek
A1 - Odemyr, Mikaëla
A1 - Okamoto, Yoshitaka
A1 - Papadopoulos, Nikos G.
A1 - Patella, Vincenzo
A1 - Pfaar, Oliver
A1 - Pham‐Thi, Nhân
A1 - Rolland, Christine
A1 - Samolinski, Boleslaw
A1 - Sheikh, Aziz
A1 - Sofiev, Mikhail
A1 - Suppli Ulrik, Charlotte
A1 - Todo‐Bom, Ana
A1 - Tomazic, Peter‐Valentin
A1 - Toppila‐Salmi, Sanna
A1 - Tsiligianni, Ioanna
A1 - Valiulis, Arunas
A1 - Valovirta, Erkka
A1 - Ventura, Maria‐Teresa
A1 - Walker, Samantha
A1 - Williams, Sian
A1 - Yorgancioglu, Arzu
A1 - Agache, Ioana
A1 - Akdis, Cezmi A.
A1 - Almeida, Rute
A1 - Ansotegui, Ignacio J.
A1 - Annesi‐Maesano, Isabella
A1 - Arnavielhe, Sylvie
A1 - Basagaña, Xavier
A1 - D. Bateman, Eric
A1 - Bédard, Annabelle
A1 - Bedolla‐Barajas, Martin
A1 - Becker, Sven
A1 - Bennoor, Kazi S.
A1 - Benveniste, Samuel
A1 - Bergmann, Karl C.
A1 - Bewick, Michael
A1 - Bialek, Slawomir
A1 - E. Billo, Nils
A1 - Bindslev‐Jensen, Carsten
A1 - Bjermer, Leif
A1 - Blain, Hubert
A1 - Bonini, Matteo
A1 - Bonniaud, Philippe
A1 - Bosse, Isabelle
A1 - Bouchard, Jacques
A1 - Boulet, Louis‐Philippe
A1 - Bourret, Rodolphe
A1 - Boussery, Koen
A1 - Braido, Fluvio
A1 - Briedis, Vitalis
A1 - Briggs, Andrew
A1 - Brightling, Christopher E.
A1 - Brozek, Jan
A1 - Brusselle, Guy
A1 - Brussino, Luisa
A1 - Buhl, Roland
A1 - Buonaiuto, Roland
A1 - Calderon, Moises A.
A1 - Camargos, Paulo
A1 - Camuzat, Thierry
A1 - Caraballo, Luis
A1 - Carriazo, Ana‐Maria
A1 - Carr, Warner
A1 - Cartier, Christine
A1 - Casale, Thomas
A1 - Cecchi, Lorenzo
A1 - Cepeda Sarabia, Alfonso M.
A1 - H. Chavannes, Niels
A1 - Chkhartishvili, Ekaterine
A1 - Chu, Derek K.
A1 - Cingi, Cemal
A1 - Correia de Sousa, Jaime
A1 - Costa, David J.
A1 - Courbis, Anne‐Lise
A1 - Custovic, Adnan
A1 - Cvetkosvki, Biljana
A1 - D'Amato, Gennaro
A1 - da Silva, Jane
A1 - Dantas, Carina
A1 - Dokic, Dejan
A1 - Dauvilliers, Yves
A1 - De Feo, Giulia
A1 - De Vries, Govert
A1 - Devillier, Philippe
A1 - Di Capua, Stefania
A1 - Dray, Gerard
A1 - Dubakiene, Ruta
A1 - Durham, Stephen R.
A1 - Dykewicz, Mark
A1 - Ebisawa, Motohiro
A1 - Gaga, Mina
A1 - El‐Gamal, Yehia
A1 - Heffler, Enrico
A1 - Emuzyte, Regina
A1 - Farrell, John
A1 - Fauquert, Jean‐Luc
A1 - Fiocchi, Alessandro
A1 - Fink‐Wagner, Antje
A1 - Fontaine, Jean‐François
A1 - Fuentes Perez, José M.
A1 - Gemicioğlu, Bilun
A1 - Gamkrelidze, Amiran
A1 - Garcia‐Aymerich, Judith
A1 - Gevaert, Philippe
A1 - Gomez, René Maximiliano
A1 - González Diaz, Sandra
A1 - Gotua, Maia
A1 - Guldemond, Nick A.
A1 - Guzmán, Maria‐Antonieta
A1 - Hajjam, Jawad
A1 - Huerta Villalobos, Yunuen R.
A1 - Humbert, Marc
A1 - Iaccarino, Guido
A1 - Ierodiakonou, Despo
A1 - Iinuma, Tomohisa
A1 - Jassem, Ewa
A1 - Joos, Guy
A1 - Jung, Ki‐Suck
A1 - Kaidashev, Igor
A1 - Kalayci, Omer
A1 - Kardas, Przemyslaw
A1 - Keil, Thomas
A1 - Khaitov, Musa
A1 - Khaltaev, Nikolai
A1 - Kleine‐Tebbe, Jorg
A1 - Kouznetsov, Rostislav
A1 - Kowalski, Marek L.
A1 - Kritikos, Vicky
A1 - Kull, Inger
A1 - La Grutta, Stefania
A1 - Leonardini, Lisa
A1 - Ljungberg, Henrik
A1 - Lieberman, Philip
A1 - Lipworth, Brian
A1 - Lodrup Carlsen, Karin C.
A1 - Lopes‐Pereira, Catarina
A1 - Loureiro, Claudia C.
A1 - Louis, Renaud
A1 - Mair, Alpana
A1 - Mahboub, Bassam
A1 - Makris, Michaël
A1 - Malva, Joao
A1 - Manning, Patrick
A1 - Marshall, Gailen D.
A1 - Masjedi, Mohamed R.
A1 - Maspero, Jorge F.
A1 - Carreiro‐Martins, Pedro
A1 - Makela, Mika
A1 - Mathieu‐Dupas, Eve
A1 - Maurer, Marcus
A1 - De Manuel Keenoy, Esteban
A1 - Melo‐Gomes, Elisabete
A1 - Meltzer, Eli O.
A1 - Menditto, Enrica
A1 - Mercier, Jacques
A1 - Micheli, Yann
A1 - Miculinic, Neven
A1 - Mihaltan, Florin
A1 - Milenkovic, Branislava
A1 - Mitsias, Dimitirios I.
A1 - Moda, Giuliana
A1 - Mogica‐Martinez, Maria‐Dolores
A1 - Mohammad, Yousser
A1 - Montefort, Steve
A1 - Monti, Ricardo
A1 - Morais‐Almeida, Mario
A1 - Mösges, Ralph
A1 - Münter, Lars
A1 - Muraro, Antonella
A1 - Murray, Ruth
A1 - Naclerio, Robert
A1 - Napoli, Luigi
A1 - Namazova‐Baranova, Leyla
A1 - Neffen, Hugo
A1 - Nekam, Kristoff
A1 - Neou, Angelo
A1 - Nordlund, Björn
A1 - Novellino, Ettore
A1 - Nyembue, Dieudonné
A1 - O'Hehir, Robyn
A1 - Ohta, Ken
A1 - Okubo, Kimi
A1 - Onorato, Gabrielle L.
A1 - Orlando, Valentina
A1 - Ouedraogo, Solange
A1 - Palamarchuk, Julia
A1 - Pali‐Schöll, Isabella
A1 - Panzner, Peter
A1 - Park, Hae‐Sim
A1 - Passalacqua, Gianni
A1 - Pépin, Jean‐Louis
A1 - Paulino, Ema
A1 - Pawankar, Ruby
A1 - Phillips, Jim
A1 - Picard, Robert
A1 - Pinnock, Hilary
A1 - Plavec, Davor
A1 - Popov, Todor A.
A1 - Portejoie, Fabienne
A1 - Price, David
A1 - Prokopakis, Emmanuel P.
A1 - Psarros, Fotis
A1 - Pugin, Benoit
A1 - Puggioni, Francesca
A1 - Quinones‐Delgado, Pablo
A1 - Raciborski, Filip
A1 - Rajabian‐Söderlund, Rojin
A1 - Regateiro, Frederico S.
A1 - Reitsma, Sietze
A1 - Rivero‐Yeverino, Daniela
A1 - Roberts, Graham
A1 - Roche, Nicolas
A1 - Rodriguez‐Zagal, Erendira
A1 - Rolland, Christine
A1 - Roller‐Wirnsberger, Regina E.
A1 - Rosario, Nelson
A1 - Romano, Antonino
A1 - Rottem, Menachem
A1 - Ryan, Dermot
A1 - Salimäki, Johanna
A1 - Sanchez‐Borges, Mario M.
A1 - Sastre, Joaquin
A1 - Scadding, Glenis K.
A1 - Scheire, Sophie
A1 - Schmid‐Grendelmeier, Peter
A1 - Schünemann, Holger J.
A1 - Sarquis Serpa, Faradiba
A1 - Shamji, Mohamed
A1 - Sisul, Juan‐Carlos
A1 - Sofiev, Mikhail
A1 - Solé, Dirceu
A1 - Somekh, David
A1 - Sooronbaev, Talant
A1 - Sova, Milan
A1 - Spertini, François
A1 - Spranger, Otto
A1 - Stellato, Cristiana
A1 - Stelmach, Rafael
A1 - Thibaudon, Michel
A1 - To, Teresa
A1 - Toumi, Mondher
A1 - Usmani, Omar
A1 - Valero, Antonio A.
A1 - Valenta, Rudolph
A1 - Valentin‐Rostan, Marylin
A1 - Pereira, Marilyn Urrutia
A1 - van der Kleij, Rianne
A1 - Van Eerd, Michiel
A1 - Vandenplas, Olivier
A1 - Vasankari, Tuula
A1 - Vaz Carneiro, Antonio
A1 - Vezzani, Giorgio
A1 - Viart, Frédéric
A1 - Viegi, Giovanni
A1 - Wallace, Dana
A1 - Wagenmann, Martin
A1 - Wang, De Yun
A1 - Waserman, Susan
A1 - Wickman, Magnus
A1 - Williams, Dennis M.
A1 - Wong, Gary
A1 - Wroczynski, Piotr
A1 - Yiallouros, Panayiotis K.
A1 - Yusuf, Osman M.
A1 - Zar, Heather J.
A1 - Zeng, Stéphane
A1 - Zernotti, Mario E.
A1 - Zhang, Luo
A1 - Shan Zhong, Nan
A1 - Zidarn, Mihaela
T1 - ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice
JF - Allergy
N2 - Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
KW - ARIA
KW - asthma
KW - CARAT
KW - digital transformation of health and care
KW - MASK
KW - rhinitis
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228339
VL - 76
IS - 1
SP - 168
EP - 190
ER -
TY - JOUR
A1 - Dohrn, Maike F.
A1 - Ihne, Sandra
A1 - Hegenbart, Ute
A1 - Medina, Jessica
A1 - Züchner, Stephan L.
A1 - Coelho, Teresa
A1 - Hahn, Katrin
T1 - Targeting transthyretin ‐ Mechanism‐based treatment approaches and future perspectives in hereditary amyloidosis
JF - Journal of Neurochemistry
N2 - The liver‐derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild‐type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate‐limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence‐specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac‐conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood–brain barrier, but its half‐life is short and liver failure a potential side effect. Amyloid‐directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR‐amyloidosis has become a model disease for pathophysiology‐based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood–brain barrier permeability.
KW - amyloid‐directed antibodies
KW - ATTRv amyloidosis
KW - familial amyloid polyneuropathy (FAP)
KW - transthyretin
KW - TTR knockdown
KW - TTR stabilization
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224481
VL - 156
IS - 6
SP - 802
EP - 818
ER -
TY - JOUR
A1 - Linsenmann, Thomas
A1 - Cattaneo, Andrea
A1 - März, Alexander
A1 - Weiland, Judith
A1 - Stetter, Christian
A1 - Nickl, Robert
A1 - Westermaier, Thomas
T1 - Combined frameless stereotactical biopsy and intraoperative cerebral angiography by 3D-rotational fluoroscopy with intravenous contrast administration: a feasibility study
JF - BMC Medical Imaging
N2 - Background
Mobile 3-dimensional fluoroscopes are an integral part of modern neurosurgical operating theatres and can also be used in combination with free available image post processing to depict cerebral vessels. In preparation of stereotactic surgery, preoperative Computed Tomography (CT) may be required for image fusion. Contrast CT may be of further advantage for image fusion as it regards the vessel anatomy in trajectory planning. Time-consuming in-hospital transports are necessary for this purpose. Mobile 3D-fluoroscopes may be used to generate a CT equal preoperative data set without an in-hospital transport. This study was performed to determine the feasibility and image quality of intraoperative 3-dimensional fluoroscopy with intravenous contrast administration in combination with stereotactical procedures.
Methods
6 patients were included in this feasibility study. After fixation in a radiolucent Mayfield clamp a rotational fluoroscopy scan was performed with 50 mL iodine contrast agent. The image data sets were merged with the existing MRI images at a planning station and visually evaluated by two observer. The operation times were compared between the frame-based and frameless systems (“skin-to-skin” and “OR entry to exit”).
Results
The procedure proves to be safe. The entire procedure from fluoroscope positioning to the transfer to the planning station took 5–6 min with an image acquisition time of 24 s. In 5 of 6 cases, the fused imaging was able to reproduce the vascular anatomy accurately and in good quality. Both time end-points were significantly shorter compared to frame-based interventions.
Conclusion
The images could easily be transferred to the planning and navigation system and were successfully merged with the MRI data set. The procedure can be completely integrated into the surgical workflow. Preoperative CT imaging or transport under anaesthesia may even be replaced by this technique in the future. Furthermore, hemorrhages can be successfully visualized intraoperatively and might prevent time delays in emergencies.
KW - 3 D rotational fluoroscopy
KW - neurosurgery
KW - stereotaxy
KW - frameless systems
KW - intraoperative imaging
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270370
VL - 21
ER -
TY - JOUR
A1 - Kann, Simone
A1 - Blessmann, Joerg
A1 - Winkelmann, Yvonne
A1 - Hansen, Jessica
A1 - Maya Amaya, Leonardo J.
A1 - Rivera Salcedo, Gadith E.
A1 - Halas, Hussein El
A1 - Schmidt‐Chanasit, Jonas
A1 - Keoviengkhone, Latdamone
A1 - Sopraseuth, Vatsana
A1 - Deschermeier, Christina
A1 - Mika, Angela
T1 - Dengue virus detection in Lao PDR and Colombia: Comparative evaluation of PCR tests
JF - Tropical Medicine & International Health
N2 - Objectives
Dengue virus (DENV) detection by polymerase chain reaction (PCR) facilitates diagnosis of dengue fever, which is the most frequent arboviral disease globally. Two studies were performed in countries with high dengue incidence, to assess the diagnostic performance of different PCR techniques.
Methods/Results
Two hundred and seventy‐nine acute phase blood samples from febrile patients were analyzed for DENV by the RealStar Dengue RT‐PCR kit (Altona Diagnostics) as gold standard in comparison with the Tropical Fever Core multiplex PCR (Fast Track Diagnostics). In total, 102 samples collected in Savannakhet Province (Lao PDR, Southeast Asia) in 2013 and 35 samples from Valledupar (Colombia, South America) tested positive for DENV by RealStar RT‐PCR. In comparison, the Tropical Fever Core multiplex PCR detected 65.0% (65/102) and 68.6% (24/35) of these samples as positive for DENV in Savannakhet and Valledupar, respectively. Diagnostic sensitivity of the multiplex PCR strongly correlated with viral load. A subset of DENV PCR‐confirmed samples was additionally tested by BNITM in house Dengue Type RT‐PCR in comparison with two commercial test kits (RealStar Dengue Type RT‐PCR [Altona Diagnostics], Dengue differentiation PCR [Fast Track Diagnostics]). The leading dengue serotype in Savannakhet was DENV‐3 (58% [29/50]), while DENV‐1 (53.8% [14/26]) was the predominant serotype found in samples collected in Valledupar by BNITM‐type PCR. However, three DENV serotypes were circulating in Valledupar and in Savannakhet. In 2015, additional studies found predominantly DENV‐4 (71% [12/17]) in Savannakhet.
Conclusions
Both studies emphasized that routine diagnostics in both regions will benefit from an expanded use of highly sensitive pan‐dengue PCRs.
KW - Colombia
KW - dengue infections
KW - dengue serotypes
KW - Lao PDR
KW - PCR diagnostics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262703
VL - 26
IS - 10
SP - 1296
EP - 1302
ER -
TY - JOUR
A1 - Freitag‐Wolf, Sandra
A1 - Munz, Matthias
A1 - Junge, Olaf
A1 - Graetz, Christian
A1 - Jockel‐Schneider, Yvonne
A1 - Staufenbiel, Ingmar
A1 - Bruckmann, Corinna
A1 - Lieb, Wolfgang
A1 - Franke, Andre
A1 - Loos, Bruno G.
A1 - Jepsen, Søren
A1 - Dommisch, Henrik
A1 - Schaefer, Arne S.
T1 - Sex‐specific genetic factors affect the risk of early‐onset periodontitis in Europeans
JF - Journal of Clinical Periodontology
N2 - Aims
Various studies have reported that young European women are more likely to develop early‐onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype‐by‐sex (G × S) interactions contribute to the increased prevalence and severity.
Materials and methods
Using the case‐only design, we tested for differences in genetic effects between men and women in 896 North‐West European early‐onset cases, using imputed genotypes from the OmniExpress genotyping array. Population‐representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population.
Results
In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S‐associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome‐wide‐associated with heel bone mineral density (CPEB4, MECOM), waist‐to‐hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13).
Conclusions
Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter‐sex phenotypic variation in early‐onset periodontitis.
KW - alveolar bone loss
KW - gene × sex interaction
KW - genetic risk
KW - heritability
KW - inflammation
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262445
VL - 48
IS - 11
SP - 1404
EP - 1413
ER -
TY - JOUR
A1 - Karimi, Sohail M.
A1 - Freund, Matthias
A1 - Wager, Brittney M.
A1 - Knoblauch, Michael
A1 - Fromm, Jörg
A1 - M. Mueller, Heike
A1 - Ache, Peter
A1 - Krischke, Markus
A1 - Mueller, Martin J.
A1 - Müller, Tobias
A1 - Dittrich, Marcus
A1 - Geilfus, Christoph-Martin
A1 - Alfaran, Ahmed H.
A1 - Hedrich, Rainer
A1 - Deeken, Rosalia
T1 - Under salt stress guard cells rewire ion transport and abscisic acid signaling
JF - New Phytologist
N2 - Soil salinity is an increasingly global problem which hampers plant growth and crop yield. Plant productivity depends on optimal water-use efficiency and photosynthetic capacity balanced by stomatal conductance. Whether and how stomatal behavior contributes to salt sensitivity or tolerance is currently unknown. This work identifies guard cell-specific signaling networks exerted by a salt-sensitive and salt-tolerant plant under ionic and osmotic stress conditions accompanied by increasing NaCl loads.
We challenged soil-grown Arabidopsis thaliana and Thellungiella salsuginea plants with short- and long-term salinity stress and monitored genome-wide gene expression and signals of guard cells that determine their function.
Arabidopsis plants suffered from both salt regimes and showed reduced stomatal conductance while Thellungiella displayed no obvious stress symptoms. The salt-dependent gene expression changes of guard cells supported the ability of the halophyte to maintain high potassium to sodium ratios and to attenuate the abscisic acid (ABA) signaling pathway which the glycophyte kept activated despite fading ABA concentrations.
Our study shows that salinity stress and even the different tolerances are manifested on a single cell level. Halophytic guard cells are less sensitive than glycophytic guard cells, providing opportunities to manipulate stomatal behavior and improve plant productivity.
KW - soil
KW - stomata
KW - abscisic acid (ABA)
KW - glycophyte Arabidopsis
KW - guard cell
KW - halophyte Thellungiella/Eutrema
KW - ion transport
KW - salt stress
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259635
VL - 231
IS - 3
ER -
TY - JOUR
A1 - Lemm, Lukas
T1 - Is there a decline of democracy in the EU between 2004 and 2016? The relevance of data selection: a replication study of Smolka (2021) and comparison of democracy measures
JF - Zeitschrift für Vergleichende Politikwissenschaft
N2 - Is there a Decline of Democracy? Democracy measurement provides the basis for answering this question. However, there are different measurement tools based on different meanings of democracy that have been shown to vary in their concept validity. Therefore, it is relevant to examine whether the results of the different measurement tools converge or diverge with respect to a potential decline of democracy. Smolka (2021) finds a decline of democracy for new and old EU states based on standardized data from the Democracy Barometer. A re-analysis using the original data of the Democracy Barometer and the Democracy Matrix can hardly replicate these results. A comparison of further measurements shows that the instruments diverge rather than converge. I therefore conclude with some thoughts on overcoming the selection problem that arises in light of these contrasts.
KW - EU member states
KW - quality of democracy
KW - decline of democracy
KW - replication studies
KW - robustness checks
KW - measuring democracy
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270107
SN - 1865-2654
VL - 15
IS - 3
ER -
TY - JOUR
A1 - Schmitt, T.
A1 - Egu, D.T.
A1 - Walter, E.
A1 - Sigmund, A.M.
A1 - Eichkorn, R.
A1 - Yazdi, A.
A1 - Schmidt, E.
A1 - Sárdy, M.
A1 - Eming, R.
A1 - Goebeler, M.
A1 - Waschke, J.
T1 - Ca\(^{2+}\) signalling is critical for autoantibody‐induced blistering of human epidermis in pemphigus
JF - British Journal of Dermatology
N2 - Background
Pemphigus is a severe bullous autoimmune skin disease. Pemphigus foliaceus (PF) is characterized by antidesmoglein (Dsg) 1 IgG causing epidermal blistering; mucosal pemphigus vulgaris (mPV) by anti‐Dsg3 IgG inducing erosions in the mucosa; and mucocutaneous pemphigus vulgaris (PV) by affecting both, with autoantibodies targeting Dsg1 and Dsg3.
Objectives
To characterize the Ca\(^{2+}\) flux pathway and delineate its importance in pemphigus pathogenesis and clinical phenotypes caused by different antibody profiles.
Methods
Immunoprecipitation, Ca\(^{2+}\) flux analysis, Western blotting, immunofluorescence staining, dissociation assays and a human skin ex vivo model were used.
Results
PV IgG and PF IgG, but neither Dsg3‐specific monoclonal antibody (AK23) nor mPV IgG, caused Ca\(^{2+}\) influx in primary human keratinocytes. Phosphatidylinositol 4‐kinase α interacts with Dsg1 but not with Dsg3. Its downstream target – phospholipase‐C‐γ1 (PLC) – was activated by PV IgG and PF IgG but not AK23 or mPV IgG. PLC releases inositol 1,4,5‐trisphosphate (IP3) causing IP3 receptor (IP3R) activation and Ca2+ flux from the endoplasmic reticulum into the cytosol, which stimulates Ca2+ release‐activated channels (CRAC)‐mediated Ca\(^{2+}\) influx. Inhibitors against PLC, IP3R and CRAC effectively blocked PV IgG and PF IgG‐induced Ca\(^{2+}\) influx; ameliorated alterations of Dsg1 and Dsg3 localization, and reorganization of keratin and actin filaments; and inhibited loss of cell adhesion in vitro. Finally, inhibiting PLC or IP3R was protective against PV IgG‐induced blister formation and redistribution of Dsg1 and Dsg3 in human skin ex vivo.
Conclusions
Ca2+‐mediated signalling is important for epidermal blistering and dependent on the autoantibody profile, which indicates different roles for signalling complexes organized by Dsg1 and Dsg3. Interfering with PLC and Ca\(^{2+}\) signalling may be a promising approach to treat epidermal manifestations of pemphigus.
KW - pemphigus
KW - epidermis
KW - Ca\(^{2+}\) signalling
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262810
VL - 185
IS - 3
SP - 595
EP - 604
ER -
TY - JOUR
A1 - Sbiera, Iuliu
A1 - Kircher, Stefan
A1 - Altieri, Barbara
A1 - Fassnacht, Martin
A1 - Kroiss, Matthias
A1 - Sbiera, Silviu
T1 - Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?
JF - Cancers
N2 - A clinically relevant proportion of adrenocortical carcinoma (ACC) cases shows a tendency to metastatic spread. The objective was to determine whether the epithelial to mesenchymal transition (EMT), a mechanism associated with metastasizing in several epithelial cancers, might play a crucial role in ACC. 138 ACC, 29 adrenocortical adenomas (ACA), three normal adrenal glands (NAG), and control tissue samples were assessed for the expression of epithelial (E-cadherin and EpCAM) and mesenchymal (N-cadherin, SLUG and SNAIL) markers by immunohistochemistry. Using real-time RT-PCR we quantified the alternative isoform splicing of FGFR 2 and 3, another known indicator of EMT. We also assessed the impact of these markers on clinical outcome. Results show that both normal and neoplastic adrenocortical tissues lacked expression of epithelial markers but strongly expressed mesenchymal markers N-cadherin and SLUG. FGFR isoform splicing confirmed higher similarity of adrenocortical tissues to mesenchymal compared to epithelial tissues. In ACC, higher SLUG expression was associated with clinical markers indicating aggressiveness, while N-cadherin expression inversely associated with these markers. In conclusion, we could not find any indication of EMT as all adrenocortical tissues lacked expression of epithelial markers and exhibited closer similarity to mesenchymal tissues. However, while N-cadherin might play a positive role in tissue structure upkeep, SLUG seems to be associated with a more aggressive phenotype.
KW - adrenocortical tissues
KW - EMT
KW - epithelial markers
KW - mesenchymal markers
KW - recurrence-free survival
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236486
SN - 2072-6694
VL - 13
IS - 7
ER -
TY - JOUR
A1 - Rajendran, Ranjithkumar
A1 - Böttiger, Gregor
A1 - Dentzien, Niklas
A1 - Rajendran, Vinothkumar
A1 - Sharifi, Bischand
A1 - Ergün, Süleyman
A1 - Stadelmann, Christine
A1 - Karnati, Srikanth
A1 - Berghoff, Martin
T1 - Effects of FGFR tyrosine kinase inhibition in OLN-93 oligodendrocytes
JF - Cells
N2 - Fibroblast growth factor (FGF) signaling is involved in the pathogenesis of multiple sclerosis (MS). Data from neuropathology studies suggest that FGF signaling contributes to the failure of remyelination in MS. In MOG\(_{35–55}\)-induced EAE, oligodendrocyte-specific deletion of FGFR1 and FGFR2 resulted in a less severe disease course, reduced inflammation, myelin and axon degeneration and changed FGF/FGFR and BDNF/TrkB signaling. Since signaling cascades in oligodendrocytes could not be investigated in the EAE studies, we here aimed to characterize FGFR-dependent oligodendrocyte-specific signaling in vitro. FGFR inhibition was achieved by application of the multi-kinase-inhibitor dovitinib and the FGFR1/2/3-inhibitor AZD4547. Both substances are potent inhibitors of FGF signaling; they are effective in experimental tumor models and patients with malignancies. Effects of FGFR inhibition in oligodendrocytes were studied by immunofluorescence microscopy, protein and gene analyses. Application of the tyrosine kinase inhibitors reduced FGFR1, phosphorylated ERK and Akt expression, and it enhanced BDNF and TrkB expression. Furthermore, the myelin proteins CNPase and PLP were upregulated by FGFR inhibition. In summary, inhibition of FGFR signaling in oligodendrocytes can be achieved by application of tyrosine kinase inhibitors. Decreased phosphorylation of ERK and Akt is associated with an upregulation of BDNF/TrkB signaling, which may be responsible for the increased production of myelin proteins. Furthermore, these data suggest that application of FGFR inhibitors may have the potential to promote remyelination in the CNS.
KW - multiple sclerosis
KW - oligodendrocytes
KW - dovitinib
KW - AZD4547
KW - FGFR signaling
KW - myelin
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239600
SN - 2073-4409
VL - 10
IS - 6
ER -