@article{KanzowRaharjaSchwartz2021,
  author    = {Kanzow, Christian and Raharja, Andreas B. and Schwartz, Alexandra},
  title     = {Sequential optimality conditions for cardinality-constrained optimization problems with applications},
  series = {Computational Optimization and Applications},
  volume    = {80},
  journal   = {Computational Optimization and Applications},
  number    = {1},
  issn      = {1573-2894},
  doi       = {10.1007/s10589-021-00298-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269052},
  pages     = {185-211},
  year      = {2021},
  abstract  = {Recently, a new approach to tackle cardinality-constrained optimization problems based on a continuous reformulation of the problem was proposed. Following this approach, we derive a problem-tailored sequential optimality condition, which is satisfied at every local minimizer without requiring any constraint qualification. We relate this condition to an existing M-type stationary concept by introducing a weak sequential constraint qualification based on a cone-continuity property. Finally, we present two algorithmic applications: We improve existing results for a known regularization method by proving that it generates limit points satisfying the aforementioned optimality conditions even if the subproblems are only solved inexactly. And we show that, under a suitable Kurdyka-Łojasiewicz-type assumption, any limit point of a standard (safeguarded) multiplier penalty method applied directly to the reformulated problem also satisfies the optimality condition. These results are stronger than corresponding ones known for the related class of mathematical programs with complementarity constraints.},
  language  = {en}
}
@article{HauserDornbergerMalzahnetal.2021,
  author    = {Hauser, T. and Dornberger, V. and Malzahn, U. and Grebe, S. J. and Liu, D. and St{\"o}rk, S. and Nauck, M. and Friedrich, N. and D{\"o}rr, M. and Wanner, C. and Krane, V. and Hammer, F.},
  title     = {The effect of spironolactone on diastolic function in haemodialysis patients},
  series = {The International Journal of Cardiovascular Imaging},
  volume    = {37},
  journal   = {The International Journal of Cardiovascular Imaging},
  number    = {6},
  issn      = {1573-0743},
  doi       = {10.1007/s10554-021-02176-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269033},
  pages     = {1927-1936},
  year      = {2021},
  abstract  = {Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in patients on maintenance haemodialysis (HD) and lacks effective treatment. We investigated the effect of spironolactone on cardiac structure and function with a specific focus on diastolic function parameters. The MiREnDa trial examined the effect of 50 mg spironolactone once daily versus placebo on left ventricular mass index (LVMi) among 97 HD patients during 40 weeks of treatment. In this echocardiographic substudy, diastolic function was assessed using predefined structural and functional parameters including E/e'. Changes in the frequency of HFpEF were analysed using the comprehensive 'HFA-PEFF score'. Complete echocardiographic assessment was available in 65 individuals (59.5 ± 13.0 years, 21.5\% female) with preserved left ventricular ejection fraction (LVEF > 50\%). At baseline, mean E/e' was 15.2 ± 7.8 and 37 (56.9\%) patients fulfilled the criteria of HFpEF according to the HFA-PEFF score. There was no significant difference in mean change of E/e' between the spironolactone group and the placebo group (+ 0.93 ± 5.39 vs. + 1.52 ± 5.94, p = 0.68) or in mean change of left atrial volume index (LAVi) (1.9 ± 12.3 ml/m\(^{2}\) vs. 1.7 ± 14.1 ml/m\(^{2}\), p = 0.89). Furthermore, spironolactone had no significant effect on mean change in LVMi (+ 0.8 ± 14.2 g/m\(^{2}\) vs. + 2.7 ± 15.9 g/m\(^{2}\); p = 0.72) or NT-proBNP (p = 0.96). Treatment with spironolactone did not alter HFA-PEFF score class compared with placebo (p = 0.63). Treatment with 50 mg of spironolactone for 40 weeks had no significant effect on diastolic function parameters in HD patients.},
  language  = {en}
}
@article{KriegelMatevskiSchuldt2021,
  author    = {Kriegel, Peter and Matevski, Dragan and Schuldt, Andreas},
  title     = {Monoculture and mixture-planting of non-native Douglas fir alters species composition, but promotes the diversity of ground beetles in a temperate forest system},
  series = {Biodiversity and Conservation},
  volume    = {30},
  journal   = {Biodiversity and Conservation},
  number    = {5},
  issn      = {1572-9710},
  doi       = {10.1007/s10531-021-02155-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269017},
  pages     = {1479-1499},
  year      = {2021},
  abstract  = {Planting non-native tree species, like Douglas fir in temperate European forest systems, is encouraged to mitigate effects of climate change. However, Douglas fir monocultures often revealed negative effects on forest biota, while effects of mixtures with native tree species on forest ecosystems are less well understood. We investigated effects of three tree species (Douglas fir, Norway spruce, native European beech), on ground beetles in temperate forests of Germany. Beetles were sampled in monocultures of each tree species and broadleaf-conifer mixtures with pitfall traps, and environmental variables were assessed around each trap. We used linear mixed models in a two-step procedure to disentangle effects of environment and tree species identity on ground beetle abundance, species richness, functional diversity and species assemblage structure. Contradictory to our expectations, ground beetle abundance and functional diversity was highest in pure Douglas fir stands, while tree mixtures showed intermediate values between pure coniferous and pure beech stands. The main drivers of these patterns were only partially dependent on tree species identity, which highlights the importance of structural features in forest stands. However, our study revealed distinct shifts in assemblage structure between pure beech and pure Douglas fir stands, which were only partially eased through mixture planting. Our findings suggest that effects of planting non-native trees on associated biodiversity can be actively modified by promoting beneficial forest structures. Nevertheless, integrating non-native tree species, even in mixtures with native trees, will invariably alter assemblage structures of associated biota, which can compromise conservation efforts targeted at typical species composition.},
  language  = {en}
}
@article{LeistnerHolzgrabe2021,
  author    = {Leistner, Adrian and Holzgrabe, Ulrike},
  title     = {Impurity Profiling of Baclofen Using Gradient HPLC-UV Method},
  series = {Chromatographia},
  volume    = {84},
  journal   = {Chromatographia},
  number    = {10},
  issn      = {1612-1112},
  doi       = {10.1007/s10337-021-04079-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268921},
  pages     = {927-935},
  year      = {2021},
  abstract  = {The GABA\(_{B}\) receptor agonist baclofen is a medication commonly used for the treatment of muscle spasticity. It is an amino acid and related to the neurotransmitter GABA. In this study, we developed a new, gradient high-performance liquid chromatography (HPLC) method for the impurity assessment of baclofen, which is appropriate for pharmacopoeial purposes. Since the impurities related to the synthesis pathway are acids, zwitterionic, or neutral, the method development is challenging. However, the separation of all components was achieved on a C18 stationary phase using a water-acetonitrile-trifluoroacetic acid gradient. A limit of detection (LOD) of at least 0.02\% was registered for all specified impurities. Additionally, CAD detection was performed to detect potential impurities lacking off a chromophore. The baclofen batches analyzed are far more pure than expected. All impurities were found below the specification limit, and thus, they can be regarded as unspecified. Moreover, the required runtime could be significantly reduced compared to the current USP or Ph. Eur. method.},
  language  = {en}
}
@article{HoehnFrimmelPrince2021,
  author    = {H{\"o}hn, Stefan and Frimmel, Hartwig E. and Prince, Westley},
  title     = {Syn-metamorphic sulfidation of the Gamsberg zinc deposit, South Africa},
  series = {Mineralogy and Petrology},
  volume    = {115},
  journal   = {Mineralogy and Petrology},
  number    = {6},
  issn      = {1438-1168},
  doi       = {10.1007/s00710-021-00764-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268574},
  pages     = {709-728},
  year      = {2021},
  abstract  = {The Mesoproterozoic Aggeneys-Gamsberg ore district, South Africa, is one of the world´s largest sulfidic base metal concentrations and well-known as a prime example of Broken Hill-type base metal deposits, traditionally interpreted as metamorphosed SEDEX deposits. Within this district, the Gamsberg deposit stands out for its huge size and strongly Zn-dominated ore ( >14 Mt contained Zn). New electron microprobe analyses and element abundance maps of sulfides and silicates point to fluid-driven sulfidation during retrograde metamorphism. Differences in the chemistry of sulfide inclusions within zoned garnet grains reflect different degrees of interaction of sulfides with high metal/sulfur-ratio with a sulfur-rich metamorphic fluid. Independent evidence of sulfidation during retrograde metamorphism comes from graphic-textured sulfide aggregates that previously have been interpreted as quenched sulfidic melts, replacement of pyrrhotite by pyrite along micro-fractures, and sulfides in phyllic alteration zones. Limited availability of fluid under retrograde conditions caused locally different degrees of segregation of Fe-rich sphalerite into Zn-rich sphalerite and pyrite, and thus considerable heterogeneity in sphalerite chemistry. The invoked sulfur-rich metamorphic fluids would have been able to sulfidize base metal-rich zones in the whole deposit and thus camouflage a potential pre-metamorphic oxidation. These findings support the recently established hypothesis of a pre-Klondikean weathering-induced oxidation event and challenge the traditional explanation of Broken Hill-type deposits as merely metamorphosed SEDEX deposits. Instead, we suggest that the massive sulfide deposits experienced a complex history, starting with initial SEDEX-type mineralization, followed by near-surface oxidation with spatial metal separation, and then sulfidation of this oxidized ore during medium- to high-grade metamorphism.},
  language  = {en}
}
@article{Ibebuchi2021,
  author    = {Ibebuchi, Chibuike Chiedozie},
  title     = {Revisiting the 1992 severe drought episode in South Africa: the role of El Ni{\~n}o in the anomalies of atmospheric circulation types in Africa south of the equator},
  series = {Theoretical and Applied Climatology},
  volume    = {146},
  journal   = {Theoretical and Applied Climatology},
  number    = {1-2},
  issn      = {1434-4483},
  doi       = {10.1007/s00704-021-03741-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268569},
  pages     = {723-740},
  year      = {2021},
  abstract  = {During strong El Ni{\~n}o events, below-average rainfall is expected in large parts of southern Africa. The 1992 El Ni{\~n}o season was associated with one of the worst drought episodes in large parts of South Africa. Using reanalysis data set from NCEP-NCAR, this study examined circulation types (CTs) in Africa south of the equator that are statistically related to the El Ni{\~n}o signal in the southwest Indian Ocean and the implication of this relationship during the 1992 drought episode in South Africa. A statistically significant correlation was found between the above-average Nino 3.4 index and a CT that features widespread cyclonic activity in the tropical southwest Indian Ocean, coupled with a weaker state of the south Indian Ocean high-pressure. During the analysis period, it was found that the El Ni{\~n}o signal enhanced the amplitude of the aforementioned CT. The impacts of the El Ni{\~n}o signal on CTs in southern Africa, which could have contributed to the 1992 severe drought episode in South Africa, were reflected in (i) robust decrease in the frequency of occurrence of the austral summer climatology pattern of atmospheric circulation that favors southeasterly moisture fluxes, advected by the South Indian Ocean high-pressure; (ii) modulation of easterly moisture fluxes, advected by the South Atlantic Ocean high-pressure, ridging south of South Africa; (iii) and enhancement of the amplitude of CTs that both enhances subsidence over South Africa, and associated with the dominance of westerlies across the Agulhas current. Under the ssp585 scenario, the analyzed climate models suggested that the impact of radiative heating on the CT significantly related to El Ni{\~n}o might result in an anomalous increase in surface pressure at the eastern parts of South Africa.},
  language  = {en}
}
@article{Ibebuchi2021,
  author    = {Ibebuchi, Chibuike Chiedozie},
  title     = {Circulation pattern controls of wet days and dry days in Free State, South Africa},
  series = {Meteorology and Atmospheric Physics},
  volume    = {133},
  journal   = {Meteorology and Atmospheric Physics},
  number    = {5},
  issn      = {1436-5065},
  doi       = {10.1007/s00703-021-00822-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268552},
  pages     = {1469-1480},
  year      = {2021},
  abstract  = {Atmospheric circulation is a vital process in the transport of heat, moisture, and pollutants around the globe. The variability of rainfall depends to some extent on the atmospheric circulation. This paper investigates synoptic situations in southern Africa that can be associated with wet days and dry days in Free State, South Africa, in addition to the underlying dynamics. Principal component analysis was applied to the T-mode matrix (variable is time series and observation is grid points at which the field was observed) of daily mean sea level pressure field from 1979 to 2018 in classifying the circulation patterns in southern Africa. 18 circulation types (CTs) were classified in the study region. From the linkage of the CTs to the observed rainfall data, from 11 stations in Free State, it was found that dominant austral winter and late austral autumn CTs have a higher probability of being associated with dry days in Free State. Dominant austral summer and late austral spring CTs were found to have a higher probability of being associated with wet days in Free State. Cyclonic/anti-cyclonic activity over the southwest Indian Ocean, explained to a good extent, the inter-seasonal variability of rainfall in Free State. The synoptic state associated with a stronger anti-cyclonic circulation at the western branch of the South Indian Ocean high-pressure, during austral summer, leading to enhanced low-level moisture transport by southeast winds was found to have the highest probability of being associated with above-average rainfall in most regions in Free State. On the other hand, the synoptic state associated with enhanced transport of cold dry air, by the extratropical westerlies, was found to have the highest probability of being associated with (winter) dryness in Free State.},
  language  = {en}
}
@article{RiedererMonoranuStrobeletal.2021,
  author    = {Riederer, P. and Monoranu, C. and Strobel, S. and Iordache, T. and Sian-H{\"u}lsmann, J.},
  title     = {Iron as the concert master in the pathogenic orchestra playing in sporadic Parkinson's disease},
  series = {Journal of Neural Transmission},
  volume    = {128},
  journal   = {Journal of Neural Transmission},
  number    = {10},
  issn      = {1435-1463},
  doi       = {10.1007/s00702-021-02414-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268539},
  pages     = {1577-1598},
  year      = {2021},
  abstract  = {About 60 years ago, the discovery of a deficiency of dopamine in the nigro-striatal system led to a variety of symptomatic therapeutic strategies to supplement dopamine and to substantially improve the quality of life of patients with Parkinson's disease (PD). Since these seminal developments, neuropathological, neurochemical, molecular biological and genetic discoveries contributed to elucidate the pathology of PD. Oxidative stress, the consequences of reactive oxidative species, reduced antioxidative capacity including loss of glutathione, excitotoxicity, mitochondrial dysfunction, proteasomal dysfunction, apoptosis, lysosomal dysfunction, autophagy, suggested to be causal for ɑ-synuclein fibril formation and aggregation and contributing to neuroinflammation and neural cell death underlying this devastating disorder. However, there are no final conclusions about the triggered pathological mechanism(s) and the follow-up of pathological dysfunctions. Nevertheless, it is a fact, that iron, a major component of oxidative reactions, as well as neuromelanin, the major intraneuronal chelator of iron, undergo an age-dependent increase. And ageing is a major risk factor for PD. Iron is significantly increased in the substantia nigra pars compacta (SNpc) of PD. Reasons for this finding include disturbances in iron-related import and export mechanisms across the blood-brain barrier (BBB), localized opening of the BBB at the nigro-striatal tract including brain vessel pathology. Whether this pathology is of primary or secondary importance is not known. We assume that there is a better fit to the top-down hypotheses and pathogens entering the brain via the olfactory system, then to the bottom-up (gut-brain) hypothesis of PD pathology. Triggers for the bottom-up, the dual-hit and the top-down pathologies include chemicals, viruses and bacteria. If so, hepcidin, a regulator of iron absorption and its distribution into tissues, is suggested to play a major role in the pathogenesis of iron dyshomeostasis and risk for initiating and progressing ɑ-synuclein pathology. The role of glial components to the pathology of PD is still unknown. However, the dramatic loss of glutathione (GSH), which is mainly synthesized in glia, suggests dysfunction of this process, or GSH uptake into neurons. Loss of GSH and increase in SNpc iron concentration have been suggested to be early, may be even pre-symptomatic processes in the pathology of PD, despite the fact that they are progression factors. The role of glial ferritin isoforms has not been studied so far in detail in human post-mortem brain tissue and a close insight into their role in PD is called upon. In conclusion, "iron" is a major player in the pathology of PD. Selective chelation of excess iron at the site of the substantia nigra, where a dysfunction of the BBB is suggested, with peripherally acting iron chelators is suggested to contribute to the portfolio and therapeutic armamentarium of anti-Parkinson medications.},
  language  = {en}
}
@article{ZechScherfClavelDanielsetal.2021,
  author    = {Zech, Linda D. and Scherf-Clavel, Maike and Daniels, Christine and Schwab, Michael and Deckert, J{\"u}rgen and Unterecker, Stefan and Herr, Alexandra S.},
  title     = {Patients with higher vitamin D levels show stronger improvement of self-reported depressive symptoms in psychogeriatric day-care setting},
  series = {Journal of Neural Transmission},
  volume    = {128},
  journal   = {Journal of Neural Transmission},
  number    = {8},
  issn      = {1435-1463},
  doi       = {10.1007/s00702-021-02385-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268525},
  pages     = {1233-1238},
  year      = {2021},
  abstract  = {Depression is a common psychiatric disorder among geriatric patients that decreases the quality of life and increases morbidity and mortality. Vitamin D as a neuro-steroid hormone might play a role in the onset and treatment of depression. In the present study, the association between depressive symptoms and vitamin D concentration in serum was evaluated. 140 patients of a psychogeriatric day-care unit were included. The geriatric depression scale (GDS) and the Hamilton depression rating scale (HDRS) were assessed at the beginning and end of treatment, GDS scores additionally 6 weeks after discharge from the day-care unit. Vitamin D levels were measured at the beginning of the treatment, routinely. Patients with levels below 30 µg/L were treated with 1000 IU vitamin D per day. There was no association between the severity of depressive symptoms and the concentration of vitamin D at the beginning of the treatment. Patients with higher vitamin D levels showed a stronger decline of depressive symptoms measured by the GDS during their stay in the day-care unit. We provide evidence that vitamin D serum levels might influence antidepressant therapy response in a geriatric population. Prospective studies are necessary to determine which patients may profit from add-on vitamin D therapy.},
  language  = {en}
}
@article{JanschZieglerForeroetal.2021,
  author    = {Jansch, Charline and Ziegler, Georg C. and Forero, Andrea and Gredy, Sina and W{\"a}ldchen, Sina and Vitale, Maria Rosaria and Svirin, Evgeniy and Z{\"o}ller, Johanna E. M. and Waider, Jonas and G{\"u}nther, Katharina and Edenhofer, Frank and Sauer, Markus and Wischmeyer, Erhard and Lesch, Klaus-Peter},
  title     = {Serotonin-specific neurons differentiated from human iPSCs form distinct subtypes with synaptic protein assembly},
  series = {Journal of Neural Transmission},
  volume    = {128},
  journal   = {Journal of Neural Transmission},
  number    = {2},
  issn      = {1435-1463},
  doi       = {10.1007/s00702-021-02303-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268519},
  pages     = {225-241},
  year      = {2021},
  abstract  = {Human induced pluripotent stem cells (hiPSCs) have revolutionized the generation of experimental disease models, but the development of protocols for the differentiation of functionally active neuronal subtypes with defined specification is still in its infancy. While dysfunction of the brain serotonin (5-HT) system has been implicated in the etiology of various neuropsychiatric disorders, investigation of functional human 5-HT specific neurons in vitro has been restricted by technical limitations. We describe an efficient generation of functionally active neurons from hiPSCs displaying 5-HT specification by modification of a previously reported protocol. Furthermore, 5-HT specific neurons were characterized using high-end fluorescence imaging including super-resolution microscopy in combination with electrophysiological techniques. Differentiated hiPSCs synthesize 5-HT, express specific markers, such as tryptophan hydroxylase 2 and 5-HT transporter, and exhibit an electrophysiological signature characteristic of serotonergic neurons, with spontaneous rhythmic activities, broad action potentials and large afterhyperpolarization potentials. 5-HT specific neurons form synapses reflected by the expression of pre- and postsynaptic proteins, such as Bassoon and Homer. The distribution pattern of Bassoon, a marker of the active zone along the soma and extensions of neurons, indicates functionality via volume transmission. Among the high percentage of 5-HT specific neurons (~ 42\%), a subpopulation of CDH13 + cells presumably designates dorsal raphe neurons. hiPSC-derived 5-HT specific neuronal cell cultures reflect the heterogeneous nature of dorsal and median raphe nuclei and may facilitate examining the association of serotonergic neuron subpopulations with neuropsychiatric disorders.},
  language  = {en}
}
@article{RotherKraftSmithetal.2021,
  author    = {Rother, Lisa and Kraft, Nadine and Smith, Dylan B. and El Jundi, Basil and Gill, Richard J. and Pfeiffer, Keram},
  title     = {A micro-CT-based standard brain atlas of the bumblebee},
  series = {Cell and Tissue Research},
  volume    = {386},
  journal   = {Cell and Tissue Research},
  number    = {1},
  issn      = {1432-0878},
  doi       = {10.1007/s00441-021-03482-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267783},
  pages     = {29-45},
  year      = {2021},
  abstract  = {In recent years, bumblebees have become a prominent insect model organism for a variety of biological disciplines, particularly to investigate learning behaviors as well as visual performance. Understanding these behaviors and their underlying neurobiological principles requires a clear understanding of brain anatomy. Furthermore, to be able to compare neuronal branching patterns across individuals, a common framework is required, which has led to the development of 3D standard brain atlases in most of the neurobiological insect model species. Yet, no bumblebee 3D standard brain atlas has been generated. Here we present a brain atlas for the buff-tailed bumblebee Bombus terrestris using micro-computed tomography (micro-CT) scans as a source for the raw data sets, rather than traditional confocal microscopy, to produce the first ever micro-CT-based insect brain atlas. We illustrate the advantages of the micro-CT technique, namely, identical native resolution in the three cardinal planes and 3D structure being better preserved. Our Bombus terrestris brain atlas consists of 30 neuropils reconstructed from ten individual worker bees, with micro-CT allowing us to segment neuropils completely intact, including the lamina, which is a tissue structure often damaged when dissecting for immunolabeling. Our brain atlas can serve as a platform to facilitate future neuroscience studies in bumblebees and illustrates the advantages of micro-CT for specific applications in insect neuroanatomy.},
  language  = {en}
}
@article{VonaMazaheriLinetal.2021,
  author    = {Vona, Barbara and Mazaheri, Neda and Lin, Sheng-Jia and Dunbar, Lucy A. and Maroofian, Reza and Azaiez, Hela and Booth, Kevin T. and Vitry, Sandrine and Rad, Aboulfazl and R{\"u}schendorf, Franz and Varshney, Pratishtha and Fowler, Ben and Beetz, Christian and Alagramam, Kumar N. and Murphy, David and Shariati, Gholamreza and Sedaghat, Alireza and Houlden, Henry and Petree, Cassidy and VijayKumar, Shruthi and Smith, Richard J. H. and Haaf, Thomas and El-Amraoui, Aziz and Bowl, Michael R. and Varshney, Gaurav K. and Galehdari, Hamid},
  title     = {A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans},
  series = {Human Genetics},
  volume    = {140},
  journal   = {Human Genetics},
  number    = {6},
  issn      = {1432-1203},
  doi       = {10.1007/s00439-020-02254-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267740},
  pages     = {915-931},
  year      = {2021},
  abstract  = {Deafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 14.96 Mb locus on chromosome 4p15.32p15.1 containing a likely pathogenic missense variant in CLRN2 (c.494C > A, NM_001079827.2) segregating with the disease. Using in vitro RNA splicing analysis, we show that the CLRN2 c.494C > A variant leads to two events: (1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and (2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identify CLRN2 as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.},
  language  = {en}
}
@article{WagnerWetzWiegeringetal.2021,
  author    = {Wagner, Johanna C. and Wetz, Anja and Wiegering, Armin and Lock, Johan F. and L{\"o}b, Stefan and Germer, Christoph-Thomas and Klein, Ingo},
  title     = {Successful surgical closure of infected abdominal wounds following preconditioning with negative pressure wound therapy},
  series = {Langenbeck's Archives of Surgery},
  volume    = {406},
  journal   = {Langenbeck's Archives of Surgery},
  number    = {7},
  issn      = {1435-2451},
  doi       = {10.1007/s00423-021-02221-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267541},
  pages     = {2479-2487},
  year      = {2021},
  abstract  = {Purpose Traditionally, previous wound infection was considered a contraindication to secondary skin closure; however, several case reports describe successful secondary wound closure of wounds "preconditioned" with negative pressure wound therapy (NPWT). Although this has been increasingly applied in daily practice, a systematic analysis of its feasibility has not been published thus far. The aim of this study was to evaluate secondary skin closure in previously infected abdominal wounds following treatment with NPWT. Methods Single-center retrospective analysis of patients with infected abdominal wounds treated with NPWT followed by either secondary skin closure referenced to a group receiving open wound therapy. Endpoints were wound closure rate, wound complications (such as recurrent infection or hernia), and perioperative data (such as duration of NPWT or hospitalization parameters). Results One hundred ninety-eight patients during 2013-2016 received a secondary skin closure after NPWT and were analyzed and referenced to 67 patients in the same period with open wound treatment after NPWT. No significant difference in BMI, chronic immunosuppressive medication, or tobacco use was found between both groups. The mean duration of hospital stay was 30 days with a comparable duration in both patient groups (29 versus 33 days, p = 0.35). Interestingly, only 7.7\% of patients after secondary skin closure developed recurrent surgical site infection and in over 80\% of patients were discharged with closed wounds requiring only minimal outpatient wound care. Conclusion Surgical skin closure following NPWT of infected abdominal wounds is a good and safe alternative to open wound treatment. It prevents lengthy outpatient wound therapy and is expected to result in a higher quality of life for patients and reduce health care costs.},
  language  = {en}
}
@article{HendricksLenschowKroissetal.2021,
  author    = {Hendricks, Anne and Lenschow, Christina and Kroiss, Matthias and Buck, Andreas and Kickuth, Ralph and Germer, Christoph-Thomas and Schlegel, Nicolas},
  title     = {Evaluation of diagnostic efficacy for localization of parathyroid adenoma in patients with primary hyperparathyroidism undergoing repeat surgery},
  series = {Langenbeck's Archives of Surgery},
  volume    = {406},
  journal   = {Langenbeck's Archives of Surgery},
  number    = {5},
  issn      = {1435-2451},
  doi       = {10.1007/s00423-021-02191-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267520},
  pages     = {1615-1624},
  year      = {2021},
  abstract  = {Purpose Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse. Methods A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated. Results Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24-48h after surgery and was achieved in 26/28 patients (92.9\%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100\%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80\%. Conclusion These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT.},
  language  = {en}
}
@article{KannapinSchmitzHansmannetal.2021,
  author    = {Kannapin, Felix and Schmitz, Tobias and Hansmann, Jan and Schlegel, Nicolas and Meir, Michael},
  title     = {Measurements of transepithelial electrical resistance (TEER) are affected by junctional length in immature epithelial monolayers},
  series = {Histochemistry and Cell Biology},
  volume    = {156},
  journal   = {Histochemistry and Cell Biology},
  number    = {6},
  issn      = {1432-119X},
  doi       = {10.1007/s00418-021-02026-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267465},
  pages     = {609-616},
  year      = {2021},
  abstract  = {The measurement of transepithelial electrical resistance (TEER) is a common technique to determine the barrier integrity of epithelial cell monolayers. However, it is remarkable that absolute TEER values of similar cell types cultured under comparable conditions show an immense heterogeneity. Based on previous observations, we hypothesized that the heterogeneity of absolute TEER measurements can not only be explained by maturation of junctional proteins but rather by dynamics in the absolute length of cell junctions within monolayers. Therefore, we analyzed TEER in epithelial cell monolayers of Caco2 cells during their differentiation, with special emphasis on both changes in the junctional complex and overall cell morphology within monolayers. We found that in epithelial Caco2 monolayers TEER increased until confluency, then decreased for some time, which was then followed by an additional increase during junctional differentiation. In contrast, permeability of macromolecules measured at different time points as 4 kDA fluorescein isothiocyanate (FITC)-dextran flux across monolayers steadily decreased during this time. Detailed analysis suggested that this observation could be explained by alterations of junctional length along the cell borders within monolayers during differentiation. In conclusion, these observations confirmed that changes in cell numbers and consecutive increase of junctional length have a critical impact on TEER values, especially at stages of early confluency when junctions are immature.},
  language  = {en}
}
@article{SalvadorBurekLoehretal.2021,
  author    = {Salvador, Ellaine and Burek, Malgorzata and L{\"o}hr, Mario and Nagai, Michiaki and Hagemann, Carsten and F{\"o}rster, Carola Y.},
  title     = {Senescence and associated blood-brain barrier alterations in vitro},
  series = {Histochemistry and Cell Biology},
  volume    = {156},
  journal   = {Histochemistry and Cell Biology},
  number    = {3},
  issn      = {1432-119X},
  doi       = {10.1007/s00418-021-01992-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267435},
  pages     = {283-292},
  year      = {2021},
  abstract  = {Progressive deterioration of the central nervous system (CNS) is commonly associated with aging. An important component of the neurovasculature is the blood-brain barrier (BBB), majorly made up of endothelial cells joined together by intercellular junctions. The relationship between senescence and changes in the BBB has not yet been thoroughly explored. Moreover, the lack of in vitro models for the study of the mechanisms involved in those changes impede further and more in-depth investigations in the field. For this reason, we herein present an in vitro model of the senescent BBB and an initial attempt to identify senescence-associated alterations within.},
  language  = {en}
}
@article{BohnertGeorgiadesMonoranuetal.2021,
  author    = {Bohnert, Simone and Georgiades, Kosmas and Monoranu, Camelia-Maria and Bohnert, Michael and B{\"u}ttner, Andreas and Ondruschka, Benjamin},
  title     = {Quantitative evidence of suppressed TMEM119 microglial immunohistochemistry in fatal morphine intoxications},
  series = {International Journal of Legal Medicine},
  volume    = {135},
  journal   = {International Journal of Legal Medicine},
  number    = {6},
  issn      = {1437-1596},
  doi       = {10.1007/s00414-021-02699-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266934},
  pages     = {2315-2322},
  year      = {2021},
  abstract  = {The aim of this pilot study was to investigate the diagnostic potential of TMEM119 as a useful microglia-specific marker in combination with immunostainings for phagocytic function and infiltrating capacity of monocytes in cases of lethal monosubstance intoxications by morphine (MOR), methamphetamine (METH), and of ethanol-associated death (ETH) respectively. Human brain tissue samples were obtained from forensic autopsies of cases with single substance abuse (MOR, n = 8; ETH, n = 10; METH, n = 9) and then compared to a cohort of cardiovascular fatalities as controls (n = 9). Brain tissue samples of cortex, white matter, and hippocampus were collected and stained immunohistochemically with antibodies against TMEM119, CD68KiM1P, and CCR2. We could document the lowest density of TMEM119-positive cells in MOR deaths with highly significant differences to the control densities in all three regions investigated. In ETH and METH deaths, the expression of TMEM119 was comparable to cell densities in controls. The results indicate that the immunoreaction in brain tissue is different in these groups depending on the drug type used for abuse.},
  language  = {en}
}
@article{BohnertWirthSchmitzetal.2021,
  author    = {Bohnert, Simone and Wirth, Christoph and Schmitz, Werner and Trella, Stefanie and Monoranu, Camelia-Maria and Ondruschka, Benjamin and Bohnert, Michael},
  title     = {Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury},
  series = {International Journal of Legal Medicine},
  volume    = {135},
  journal   = {International Journal of Legal Medicine},
  number    = {4},
  issn      = {1437-1596},
  doi       = {10.1007/s00414-021-02606-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266929},
  pages     = {1525-1535},
  year      = {2021},
  abstract  = {The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.},
  language  = {en}
}
@article{NedopilShekharHowelletal.2021,
  author    = {Nedopil, Alexander J. and Shekhar, Adithya and Howell, Stephen M. and Hull, Maury L.},
  title     = {An insert with less than spherical medial conformity causes a loss of passive internal rotation after calipered kinematically aligned TKA},
  series = {Archives of Orthopaedic and Trauma Surgery},
  volume    = {141},
  journal   = {Archives of Orthopaedic and Trauma Surgery},
  number    = {12},
  issn      = {1434-3916},
  doi       = {10.1007/s00402-021-04054-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266710},
  pages     = {2287-2294},
  year      = {2021},
  abstract  = {Introduction In total knee arthroplasty (TKA), the level of conformity, a medial stabilized (MS) implant, needs to restore native (i.e., healthy) knee kinematics without over-tensioning the flexion space when the surgeon chooses to retain the posterior cruciate ligament (PCL) is unknown. Whether an insert with a medial ball-in-socket conformity and lateral flat surface like the native knee or a less than spherical medial conformity restores higher and closer to native internal tibial rotation without anterior lift-off, an over-tension indicator, when implanted with calipered kinematic alignment (KA), is unknown. Methods and Materials Two surgeons treated 21 patients with calipered KA and a PCL retaining MS implant. Validated verification checks that restore native tibial compartment forces in passive flexion without release of healthy ligaments were used to select the optimal insert thickness. A goniometer etched onto trial inserts with the ball-in-socket and the less than spherical medial conformity measured the tibial rotation relative to the femoral component at extension and 90° and 120° flexion. The surgeon recorded the incidence of anterior lift-off of the insert. Results The insert with the medial ball-in-socket and lateral flat surface restored more internal tibial rotation than the one with less than spherical medial conformity, with mean values of 19° vs. 17° from extension to 90° flexion (p < 0.01), and 23° vs. 20°-120° flexion (p < 0.002), respectively. There was no anterior lift-off of the insert at 90° and 120° flexion. Conclusion An MS insert with a medial ball-in-socket and lateral flat surface that matches the native knee's spherical conformity restores native tibial internal rotation when implanted with calipered KA and PCL retention without over-tensioning the flexion space.},
  language  = {en}
}
@article{SzymskiAschenbachKrutschetal.2021,
  author    = {Szymski, Dominik and Aschenbach, Leonard and Krutsch, Volker and Alt, Volker and Meffert, Rainer and Krutsch, Werner and Fehske, Kai},
  title     = {Injury epidemiology in men's professional team sports: is media analysis helpful?},
  series = {Archives of Orthopaedic and Trauma Surgery},
  volume    = {141},
  journal   = {Archives of Orthopaedic and Trauma Surgery},
  number    = {4},
  issn      = {1434-3916},
  doi       = {10.1007/s00402-020-03743-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266690},
  pages     = {655-661},
  year      = {2021},
  abstract  = {Introduction Epidemiological injury surveillance in professional sports is often based on online media analysis in order to collect necessary data. However, the validation of this study protocol is lacking. Therefore, this study aimed to identify the validity of injury surveillance in men's professional team sports based on media reports. Methods In a retrospective cohort study, the validity of media-data-relating injuries was investigated in participating teams of the highest two German divisions in men's professional basketball (BB) and handball (HB) in the season 2018/2019. Injury protocols completed by the team physicians were compared to those of sports media injury reports. Results The study population was composed of 133 athletes (54 BB and 79 HB). Of 343 injuries reported by the team physicians, 151 (44\%) could be identified by means of sports media reports. Severe injuries (n = 75, 72\%) were reported more likely in sports media compared to less severe injuries (n = 76, 32\%, p < 0.00001). Odds ratio (OR) was 5.33 (95\% CI 3.22-8.82). No differences regarding injury reporting could be seen between the two team sports. Conclusion For severe injuries, media analysis may be a sufficient method for data collection in popular men's professional ball sports. An underestimation of true injury prevalence lies within the range of previous reported investigations concerning the validation of injury surveillance methods. Non-severe injuries could not be verified via media analysis in professional handball and basketball.},
  language  = {en}
}