Publications by authors named "Uwe Schmidt"

64 Publications

Reactions of diborenes with terminal alkynes: mechanisms of ligand-controlled -selective hydroalkynylation, cycloaddition and C[triple bond, length as m-dash]C triple bond scission.

Chem Sci 2021 Jul 21;12(27):9506-9515. Epub 2021 Jun 21.

Institute for Inorganic Chemistry, Julius-Maximilians-Universität Würzburg Am Hubland 97074 Würzburg Germany

The reactions of terminal acetylenes with doubly Lewis base-stabilised diborenes resulted in different outcomes depending on the nature of the ligands at boron and the conformation of the diborene (cyclic acyclic). N-heterocyclic carbene (NHC)-stabilised diborenes tended to undergo -selective hydroalkynylation at room temperature, whereas [2 + 2] cycloaddition was observed at higher temperatures, invariably followed by a C-N bond activation at one NHC ligand, leading to the ring-expansion of the initially formed BCBC ring and formation of novel boron-containing heterocycles. For phosphine-stabilised diborenes only [2 + 2] cycloaddition was observed, followed by a rearrangement of the resulting 1,2-dihydro-1,2-diborete to the corresponding 1,3-isomer, which amounts to complete scission of both the B[double bond, length as m-dash]B double and C[triple bond, length as m-dash]C triple bonds of the reactants. The elusive 1,2-isomer was finally trapped by using a cyclic phosphine-stabilised diborene, which prevented rearrangement to the 1,3-isomer. Extensive density functional theory (DFT) calculations provide a rationale for the selectivity observed.
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http://dx.doi.org/10.1039/d1sc02081aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314202PMC
July 2021

Development and testing of a summative video-based e-examination in relation to an OSCE for measuring communication-related factual and procedural knowledge of medical students.

GMS J Med Educ 2021 15;38(3):Doc70. Epub 2021 Mar 15.

University Medical Center, Johannes Gutenberg University Mainz, Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy, Department of Medical Psychology and Medical Sociology, Mainz, Germany.

In the context of educating medical students, testing of competence in medical communication is carried out primarily with the Objective Structured Clinical Examination [1]. This makes it possible to assess practical performance, but it is resource-intensive and has a negative impact on test quality. The project "Digital test tool for measuring communication skills in medical studies" (digiRole) was funded by the BMBF (Federal Ministry of Education and Research) and its objective was to develop digital formats as electronic versions of an OSCE in order to test the communication competency of medical students. Such digital forms of examination should be cost-effective, be relevant to clinical practice and have high psychometric quality. In terms of content, the examination questions should incorporate factual and procedural knowledge as components of communication competency, although we assumed that procedural knowledge is more relevant than facutal knowledge to OSCE performance. This article describes the development and testing of a video-based, communication-related e-examination that is relevant to passing the test, which is the first milestone of the overall project. We produced videos and related exam questions in the form of a situational judgement test [2] related to medical psychology and medical sociology, based on the educational content of a preclinical course on doctor-patient communication at the Mainz University Medical Center. In the summer semester of 2018, 226 students sat for this video-based single-choice e-examination (VSE). In the winter semester of 2018/2019, a different cohort of 192 students participated in the VSE as well as a tried-and-tested communication OSCE with five stations [3]. The internal consistencies for the VSE in the summer semester of 2018 were α=.55, in the winter semester 2018/19 with α=.62 and for the OSCE with α=.60. There was a positive correlation between the performance of the students with the VSE and that with the OSCE (r=.21, p≤.01). Principal Axis Analyses did not reveal any dimensioning in terms of factual and procedural knowledge. In the evaluation, the majority of the students stated that the VSE was quite relevant to the practise of medical communication and were in favour of retaining this form of examination. The correlation between the VSE and the OSCE is relatively low, so that the VSE in this form is not a satisfactory predictor of an OSCE result. In terms of internal consistency, the VSE and the OSCE produced an almost identical result. It can also be assumed that the VSE can achieve a high degree of objectivity with the use of standardised video-based examinations as well as greater resource efficiency than OSCEs.
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http://dx.doi.org/10.3205/zma001466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994868PMC
March 2021

Increase of Yield, Lycopene, and Lutein Content in Tomatoes Grown Under Continuous PAR Spectrum LED Lighting.

Front Plant Sci 2021 26;12:611236. Epub 2021 Feb 26.

Division Biosystems Engineering, Faculty of Life Sciences, Albrecht Daniel Thaer - Institute of Agricultural and Horticultural Sciences, Humboldt-Universität zu Berlin, Berlin, Germany.

Light emitting diodes (LEDs) are an energy efficient alternative to high-pressure sodium (HPS) lighting in tomato cultivation. In the past years, we have learned a lot about the effect of red and blue LEDs on plant growth and yield of tomatoes. From previous studies, we know that plants absorb and utilize most of the visible spectrum for photosynthesis. This part of the spectrum is referred to as the photosynthetically active radiation (PAR). We designed a LED fixture with an emission spectrum that partially matches the range of 400 to 700 nm and thus partially covers the absorption spectrum of photosynthetic pigments in tomato leaves. Tomato plants grown under this fixture were significantly taller and produced a higher fruit yield (14%) than plants grown under HPS lighting. There was no difference in the number of leaves and trusses, leaf area, stem diameter, the electron transport rate, and the normalized difference vegetation index. Lycopene and lutein contents in tomatoes were 18% and 142% higher when they were exposed to the LED fixture. However, the ß-carotene content was not different between the light treatments. Transpiration rate under LED was significantly lower (40%), while the light use efficiency (LUE) was significantly higher (19%) compared to HPS lighting. These data show that an LED fixture with an emission spectrum covering the entire PAR range can improve LUE, yields, and content of secondary metabolites in tomatoes compared to HPS lighting.
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http://dx.doi.org/10.3389/fpls.2021.611236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952642PMC
February 2021

Tree rings reveal signs of Europe's sustainable forest management long before the first historical evidence.

Sci Rep 2020 12 11;10(1):21832. Epub 2020 Dec 11.

Department of Geography, University of Cambridge, Downing Place, Cambridge, CB2 3EN, UK.

To satisfy the increasing demand for wood in central Europe during medieval times, a new system of forest management was developed, one far superior to simple coppicing. The adoption of a sophisticated, Coppice-with-Standards (CWS) management practice created a two-storey forest structure that could provide fuelwood as well as construction timber. Here we present a dendrochronological study of actively managed CWS forests in northern Bavaria to detect the radial growth response to cyclical understorey harvesting in overstorey oaks (Quercus sp.), so-called standards. All modern standards exhibit rapid growth releases every circa 30 years, most likely caused by regular understorey management. We further analyse tree-ring width patterns in 2120 oak timbers from historical buildings and archaeological excavations in southern Germany and north-eastern France, dating between 300 and 2015 CE, and succeeded in identifying CWS growth patterns throughout the medieval period. Several potential CWS standards even date to the first millennium CE, suggesting CWS management has been in practice long before its first mention in historical documents. Our dendrochronological approach should be expanded routinely to indentify the signature of past forest management practices in archaeological and historical oak wood.
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http://dx.doi.org/10.1038/s41598-020-78933-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733517PMC
December 2020

Tuneable reduction of cymantrenylboranes to diborenes or borylene-derived boratafulvenes.

Chem Commun (Camb) 2020 Nov;56(94):14809-14812

Institute for Inorganic Chemistry, Julius-Maximilians-Universität Würzburg, Am Hubland, 97074 Würzburg, Germany. and Institute for Sustainable Chemistry & Catalysis with Boron, Julius-Maximilians-Universität Würzburg, Am Hubland, 97074 Würzburg, Germany.

Whereas the reduction of N-heterocyclic carbene (NHC)-stabilised cymantrenyldibromoboranes, (NHC)BBr2Cym, in benzene results in the formation of the corresponding diborenes (NHC)2B2Cym2, a change of solvent to THF yields a borylene analogue of the form (NHC)2BCym, stabilised through a boratafulvene/borafulvenium conformation.
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http://dx.doi.org/10.1039/d0cc06398cDOI Listing
November 2020

Practical sensorless aberration estimation for 3D microscopy with deep learning.

Opt Express 2020 Sep;28(20):29044-29053

Estimation of optical aberrations from volumetric intensity images is a key step in sensorless adaptive optics for 3D microscopy. Recent approaches based on deep learning promise accurate results at fast processing speeds. However, collecting ground truth microscopy data for training the network is typically very difficult or even impossible thereby limiting this approach in practice. Here, we demonstrate that neural networks trained only on simulated data yield accurate predictions for real experimental images. We validate our approach on simulated and experimental datasets acquired with two different microscopy modalities and also compare the results to non-learned methods. Additionally, we study the predictability of individual aberrations with respect to their data requirements and find that the symmetry of the wavefront plays a crucial role. Finally, we make our implementation freely available as open source software in Python.
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http://dx.doi.org/10.1364/OE.401933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679184PMC
September 2020

Closed mitosis requires local disassembly of the nuclear envelope.

Nature 2020 09 26;585(7823):119-123. Epub 2020 Aug 26.

MRC Laboratory for Molecular Cell Biology, London, UK.

At the end of mitosis, eukaryotic cells must segregate the two copies of their replicated genome into two new nuclear compartments. They do this either by first dismantling and later reassembling the nuclear envelope in an 'open mitosis' or by reshaping an intact nucleus and then dividing it into two in a 'closed mitosis'. Mitosis has been studied in a wide variety of eukaryotes for more than a century, but how the double membrane of the nuclear envelope is split into two at the end of a closed mitosis without compromising the impermeability of the nuclear compartment remains unknown. Here, using the fission yeast Schizosaccharomyces pombe (a classical model for closed mitosis), genetics, live-cell imaging and electron tomography, we show that nuclear fission is achieved via local disassembly of nuclear pores within the narrow bridge that links segregating daughter nuclei. In doing so, we identify the protein Les1, which is localized to the inner nuclear envelope and restricts the process of local nuclear envelope breakdown to the bridge midzone to prevent the leakage of material from daughter nuclei. The mechanism of local nuclear envelope breakdown in a closed mitosis therefore closely mirrors nuclear envelope breakdown in open mitosis, revealing an unexpectedly high conservation of nuclear remodelling mechanisms across diverse eukaryotes.
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http://dx.doi.org/10.1038/s41586-020-2648-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610560PMC
September 2020

Crop Photosynthetic Performance Monitoring Based on a Combined System of Measured and Modelled Chloroplast Electron Transport Rate in Greenhouse Tomato.

Front Plant Sci 2020 10;11:1038. Epub 2020 Jul 10.

Department of Biosystems Engineering, Humboldt University of Berlin, Berlin, Germany.

Combining information of plant physiological processes with climate control systems can improve control accuracy in controlled environments as greenhouses and plant factories. Through that, resource optimization can be achieved. To predict the plant physiological processes and implement them in control actions of interest, a reliable monitoring system and a capable control system are needed. In this paper, we focused on the option to use real-time crop monitoring for precision climate control in greenhouses. For that, we studied the processes and external factors influencing leaf net CO assimilation rate ( , µmol CO m s) as possible variables of a plant performance indicator. While measured greenhouse environmental variables such as light, temperature, or humidity showed a direct relation between and light-quantum yield of photosystem II (Φ), we defined three objectives: (1) to explore the relationship between climate variables and , as well as Φ; (2) create a simple and reliable method for real-time prediction of with continuously Φ measurements; and (3) calibrate parameters to predict chloroplast electron transport rate as input in modelling. Due to practical obstacles in measuring CO gas-exchange in commercial production, we explored a method to predict by measuring Φ of leaves in a commercial hydroponic greenhouse tomato crop ("Pureza"). We calculated with two different approaches based on either the negative exponential response model with simplified biochemical equations (marked as Model I) or the non-rectangular hyperbola full biochemical photosynthetic models (marked as Model II). Using Model I can only be used to predict with large uncertainty (R 0.64; RMSE 2.21), while using Φ as input to Model II could be used to improve the prediction accuracy of (R 0.71; RMSE 1.98). Our results suggests that (1) Φ light signals can be used to predict net photosynthesis rate with high accuracy; (2) a parameterized photosynthetic electron transport rate model is suitable predicting measured electron transport rate () and . The system can be used as decision support system (DSS) for plant and crop performance monitoring when leaf-dynamics are up-scaled to the plant or crop level.
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http://dx.doi.org/10.3389/fpls.2020.01038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381275PMC
July 2020

Live Imaging of a Hyperthermophilic Archaeon Reveals Distinct Roles for Two ESCRT-III Homologs in Ensuring a Robust and Symmetric Division.

Curr Biol 2020 07 4;30(14):2852-2859.e4. Epub 2020 Jun 4.

MRC-Laboratory for Molecular Cell Biology, UCL, Gower Street, London WC1E 6BT, UK; Institute for the Physics of Living Systems, UCL, London WC1E 6BT, UK. Electronic address:

Live-cell imaging has revolutionized our understanding of dynamic cellular processes in bacteria and eukaryotes. Although similar techniques have been applied to the study of halophilic archaea [1-5], our ability to explore the cell biology of thermophilic archaea has been limited by the technical challenges of imaging at high temperatures. Sulfolobus are the most intensively studied members of TACK archaea and have well-established molecular genetics [6-9]. Additionally, studies using Sulfolobus were among the first to reveal striking similarities between the cell biology of eukaryotes and archaea [10-15]. However, to date, it has not been possible to image Sulfolobus cells as they grow and divide. Here, we report the construction of the Sulfoscope, a heated chamber on an inverted fluorescent microscope that enables live-cell imaging of thermophiles. By using thermostable fluorescent probes together with this system, we were able to image Sulfolobus acidocaldarius cells live to reveal tight coupling between changes in DNA condensation, segregation, and cell division. Furthermore, by imaging deletion mutants, we observed functional differences between the two ESCRT-III proteins implicated in cytokinesis, CdvB1 and CdvB2. The deletion of cdvB1 compromised cell division, causing occasional division failures, whereas the ΔcdvB2 exhibited a profound loss of division symmetry, generating daughter cells that vary widely in size and eventually generating ghost cells. These data indicate that DNA separation and cytokinesis are coordinated in Sulfolobus, as is the case in eukaryotes, and that two contractile ESCRT-III polymers perform distinct roles to ensure that Sulfolobus cells undergo a robust and symmetrical division.
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http://dx.doi.org/10.1016/j.cub.2020.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372223PMC
July 2020

Synergistic Effects of Forensic Medicine and Traumatology: Comparison of Clinical Diagnosis Autopsy Findings in Trauma-Related Deaths.

World J Surg 2020 04;44(4):1137-1148

University Center of Orthopaedics and Traumatology, AG Polytrauma, University Medicine Carl Gustav Carus, Technical University, Fetscherstrasse 74, 01307, Dresden, Germany.

Background: Trauma is the third leading cause of death worldwide after cardiovascular and oncologic diseases. Predominant causes of trauma-related death (TD) are severe traumatic brain injury (sTBI), hemorrhagic shock, and multiple organ failure. An analysis of TD is required in order to review the quality of trauma care and grasp how well the entire trauma network functions, especially for the most severely injured patients. Furthermore, autopsies not only reveal hidden injuries, but also verify clinical assumed causes of death.

Material: During the study period of 3 years, a total of 517 trauma patients were admitted to our supraregional University Centre of Orthopaedics and Traumatology in Dresden. 13.7% (71/517) of the patients died after trauma, and in 25 cases (35.2%), a forensic autopsy was instructed by the federal prosecutor. The medical records, death certificates, and autopsy reports were retrospectively evaluated and the clinical findings matched to autopsy results.

Results: The observed mortality rates (13.7%) were 4.2% less than expected by the calculated RISC II probability of survival (mortality rate of 17.9%). The most frequent trauma victims were due to falls >3 m (n = 29), followed by traffic accidents (n = 28). The median ISS was 34, IQR 25, and the median New ISS (NISS) was 50, IQR 32. Locations of death were in emergency department (23.9%), ICU (73.2%), OR and ward (1.4%, respectively). Clinicians classified 47.9% of deaths due to sTBI (n = 34), followed by 9.9% thoracic trauma and multiple organ failure (n = 7), 8.4% multiple trauma (n = 6), and 2.8% hypoxia and exsanguination (n = 2). In 18.3%, cases were unspecific or other causes of death recorded on the death certificates. Evident differences with evident clinical consequences were ascertained in 4% (n = 1) and marginal clinical consequences in 24% (6/25). In 16% (4/25), marginal differences with minor forensic consequences were revealed.

Conclusions: Even in a supraregional trauma center, specialized in multiple trauma management (4.2% survival benefit), room for improvement exists in more than a quarter of all casualties. This underlines the need for higher autopsy rates to uncover missed injuries and to understand the pathomechanism in each trauma fatality. This would also help to uncover potential insufficiencies in clinical routines with regard to diagnostics. The interdisciplinary cooperation of trauma surgeons and forensic pathologists can increase the quality of trauma patient care.
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http://dx.doi.org/10.1007/s00268-019-05347-7DOI Listing
April 2020

CLIJ: GPU-accelerated image processing for everyone.

Nat Methods 2020 01;17(1):5-6

Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.

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http://dx.doi.org/10.1038/s41592-019-0650-1DOI Listing
January 2020

Cell-Based Optimization of Covalent Reversible Ketoamide Inhibitors Bridging the Unprimed to the Primed Site of the Proteasome β5 Subunit.

ChemMedChem 2019 12 12;14(23):2005-2022. Epub 2019 Nov 12.

Clemens-Schoepf-Institute for Organic Chemistry & Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Str. 4, 64287, Darmstadt, Germany.

The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1' by a 3-phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.
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http://dx.doi.org/10.1002/cmdc.201900472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916368PMC
December 2019

trans-Selective Insertional Dihydroboration of a cis-Diborene: Synthesis of Linear sp -sp -sp -Triboranes and Subsequent Cationization.

Angew Chem Int Ed Engl 2020 Jan 12;59(1):325-329. Epub 2019 Nov 12.

Institut für Anorganische Chemie and Institute for Sustainable Chemistry & Catalysis with Boron, Julius-Maximilians-Universität Wüzburg, Am Hubland, 97074, Würzburg, Germany.

The reaction of aryl- and amino(dihydro)boranes with dibora[2]ferrocenophane 1 leads to the formation 1,3-trans-dihydrotriboranes by formal hydrogenation and insertion of a borylene unit into the B=B bond. The aryltriborane derivatives undergo reversible photoisomerization to the cis-1,2-μ-H-3-hydrotriboranes, while hydride abstraction affords cationic triboranes, which represent the first doubly base-stabilized B H analogues.
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http://dx.doi.org/10.1002/anie.201911645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972689PMC
January 2020

Spontaneous trans-Selective Transfer Hydrogenation of Apolar Boron-Boron Double Bonds.

Angew Chem Int Ed Engl 2019 Jul 6;58(29):9782-9786. Epub 2019 Jun 6.

Institut für Anorganische Chemie & the Institute for Sustainable Chemistry & Catalysis with Boron, Julius-Maximilians-Universität Würzburg, Am Hubland, 97074, Würzburg, Germany.

The transfer hydrogenation of N-heterocyclic carbene (NHC)-supported diborenes with dimethylamine borane proceeds with high selectivity for the trans-1,2-dihydrodiboranes. DFT calculations, supported by kinetic studies and deuteration experiments, suggest a stepwise proton-first-hydride-second reaction mechanism via an intermediate μ-hydrodiboronium dimethylaminoborate ion pair.
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http://dx.doi.org/10.1002/anie.201902656DOI Listing
July 2019

["Crystal" and Pregnancy - The Preliminary Results of a Retrospective Study on the Course of Pregnancy and Delivery of Women Consuming Methamphetamine].

Z Geburtshilfe Neonatol 2019 Aug 20;223(4):221-229. Epub 2019 Feb 20.

Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Carl Gustav Carus Dresden, Dresden.

Introduction: It can be observed that there is an increase in the methamphetamine (MA) consumption in Saxony (Federal Republic of Germany). There is so far no data available in German speaking countries about the risk of MA consumption in pregnancy or delivery.

Methods: The data from all pregnant women who were examined or delivered at the Clinic for Obstetrics and Gynaecology between 2010-2015 were retrospectively searched for MA consumption. 119 pregnancies with 113 deliveries of 115 women consuming MA could be evaluated. 88 women admitted the consumption according to the history, 28 women denied it and there was no information available in the records of 3 cases. 113 women agreed to test MA in blood and 93 cases were positive (28 cases of them with low-dose consumption). The statistical analysis was performed by the Institute for Medical Informatics and Biometry. The data driven from the quality control report of the department of Gynaecology in 2015 was used as a control group.

Results: MA-consumers are significantly younger, without a permanent relationship, without a job and have a low education level. The first detection of the pregnancy was late and the number of performed routine examinations including ultrasound assessment was lower compared to the controls. 7 women had no routine examination. The number of premature contractions, cervical insufficiency and gestational diabetes were significantly higher. The number of patients needing tocolysis, antenatal glucocorticoid treatment for prevention of neonatal respiratory distress syndrome or in-patient care was significantly higher in patients consuming MA. The number of amniotic infection syndrome and premature rupture of membranes were higher. The rate of intrauterine fetal death was 3,5% which was much higher than the rate of control group (0,2%).

Discussion: The MA-consumption increases the risk for mother and child significantly during the pregnancy and delivery (pregnancy complications, premature delivery, increased rate of abortion, intrauterine death). A special attention must be taken for the young pregnant, non-working women without a partner who do not take the routine examinations in account or start having them late.
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http://dx.doi.org/10.1055/a-0831-3642DOI Listing
August 2019

Oxidative addition of arsenic halides to platinum(0).

Dalton Trans 2019 Mar;48(11):3547-3550

Institut für Anorganische Chemie, Julius-Maximilians-Universität Würzburg, Am Hubland, 97074 Würzburg, Germany.

Reaction of AsCl3 with Pt(0) complexes [Pt(PCy3)2], [Pt(PCy3)(IMes)] and [Pt(IMes)2] (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) resulted in oxidative addition of As-Cl bonds at the Pt centres to form complexes of the form trans-[PtCl(AsCl2)L2]. Two of these compounds were characterised by X-ray diffraction, making them the first structurally characterised examples of AsX2 ligands (X = halogen). AsBr3 also underwent oxidative addition to [Pt(PCy3)2], forming trans-[PtBr(AsBr2)(PCy3)2] in situ, as judged by 31P NMR spectroscopy. This reaction was unselective, yielding several products, of which a Pt3As2 cluster could be identified by single-crystal X-ray diffraction.
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http://dx.doi.org/10.1039/c8dt04995eDOI Listing
March 2019

Child Abuse or Bleeding Disorder-An Interdisciplinary Approach.

Hamostaseologie 2019 Feb 25;39(1):28-35. Epub 2019 Jan 25.

Institute of Forensic Medicine, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Sachsen, Germany.

Children with an unexplained bleeding tendency are frequently referred to a haemostaseologist for further evaluation. Careful standardized history taking and clinical evaluation should allow for distinguishing bleeds after minor injury and trauma which are very common in all children. However, in two groups of children bleeding symptoms may be more significant than expected: those with an underlying coagulation disorder and those who have been subjected to physical child abuse. The coexistence of child abuse and a bleeding disorder must always be considered. An extended coagulation diagnostic is required if the morphology of bleedings is not clearly suspicious for child abuse and in the absence of typical concomitant injuries, e.g., bone fractures. An interdisciplinary approach involving a forensic pathologist and a paediatric haemostaseologist for assessment of bleeding symptoms, the explanation of the clinical findings, and the critical evaluation of laboratory results are essential in such cases. This review is focussed on symptoms in accidental and nonaccidental injuries in children assisting haemostaseologists in decision making in cases of child protection issues.
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http://dx.doi.org/10.1055/s-0039-1677714DOI Listing
February 2019

Content-aware image restoration: pushing the limits of fluorescence microscopy.

Nat Methods 2018 12 26;15(12):1090-1097. Epub 2018 Nov 26.

Center for Systems Biology Dresden, Dresden, Germany.

Fluorescence microscopy is a key driver of discoveries in the life sciences, with observable phenomena being limited by the optics of the microscope, the chemistry of the fluorophores, and the maximum photon exposure tolerated by the sample. These limits necessitate trade-offs between imaging speed, spatial resolution, light exposure, and imaging depth. In this work we show how content-aware image restoration based on deep learning extends the range of biological phenomena observable by microscopy. We demonstrate on eight concrete examples how microscopy images can be restored even if 60-fold fewer photons are used during acquisition, how near isotropic resolution can be achieved with up to tenfold under-sampling along the axial direction, and how tubular and granular structures smaller than the diffraction limit can be resolved at 20-times-higher frame rates compared to state-of-the-art methods. All developed image restoration methods are freely available as open source software in Python, FIJI, and KNIME.
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http://dx.doi.org/10.1038/s41592-018-0216-7DOI Listing
December 2018

Dibora[2]ferrocenophane: A Carbene-Stabilized Diborene in a Strained cis-Configuration.

Angew Chem Int Ed Engl 2017 01 20;56(3):889-892. Epub 2016 Dec 20.

Department of Chemistry, School of Life Sciences, University of Sussex, Brighton, BN1 9QJ, Sussex, UK.

Unsaturated bridges that link the two cyclopentadienyl ligands together in strained ansa metallocenes are rare and limited to carbon-carbon double bonds. The synthesis and isolation of a strained ferrocenophane containing an unsaturated two-boron bridge, isoelectronic with a C=C double bond, was achieved by reduction of a carbene-stabilized 1,1'-bis(dihaloboryl)ferrocene. A combination of spectroscopic and electrochemical measurements as well as density functional theory (DFT) calculations was used to assess the influence of the unprecedented strained cis configuration on the optical and electrochemical properties of the carbene-stabilized diborene unit. Initial reactivity studies show that the dibora[2]ferrocenophane is prone to boron-boron double bond cleavage reactions.
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http://dx.doi.org/10.1002/anie.201609601DOI Listing
January 2017

Impact of Prosthesis Length on Tympanic Membrane's and Annular Ligament's Stiffness and the Resulting Middle Ear Sound Transmission.

Otol Neurotol 2016 10;37(9):e369-76

*Carl Gustav Carus Faculty of Medicine, Otorhinolaryngology, Head and Neck Surgery †Carl Gustav Carus Faculty of Medicine, Legal Medicine, TU Dresden, Dresden, Germany.

Hypothesis: Prosthesis' length creates tension in ossicular reconstructions, which directly effects the middle ear sound transmission.

Background: Relatively long prostheses are often used to stabilize the middle ear reconstruction to prevent dislocation. Thereby, tension on the flexible components such as the tympanic membrane (TM) and the annular ligament (AL) is increased. Only little is known on the amount of displacement-related stiffening of the TM and AL, as well as the consecutive reduction in middle ear transfer function (METF).

Methods: An expandable total ossicular replacement prosthesis was tensionfree inserted in nine cadaveric temporal bones between the malleus handle and the stapes footplate. Upon heat activation the prosthesis was lengthened, thus inducing tension on the reconstruction. The METF was assessed before and after elongation. TM's and AL's stiffness were determined by measuring their force-displacement characteristics.

Results: Upon activation the prostheses were elongated between 50 and 200 μm. A frequency-dependent METF reduction was measured with a decrease of 5 to 25 dB below 1.0 kHz. At frequencies >2.0 kHz the reduction was less prominent or the METF showed even an improvement of up to 10 dB. TM's stiffness remained constant during the elongation-induced displacement, whereas the AL's stiffness increased. The METF reduction below 1.0 kHz correlated with the increasing AL's stiffness.

Conclusion: Tension has a significant impact on the METF after middle ear reconstruction. As little tension as possible should be used to enable best sound transmission. Stabilization of prosthesis should be achieved with dislocation devices to ensure secure coupling to the ossicular remnants without creating additional tension.
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http://dx.doi.org/10.1097/MAO.0000000000001064DOI Listing
October 2016

Reuse of Organomineral Substrate Waste from Hydroponic Systems as Fertilizer in Open-Field Production Increases Yields, Flavonoid Glycosides, and Caffeic Acid Derivatives of Red Oak Leaf Lettuce (Lactuca sativa L.) Much More than Synthetic Fertilizer.

J Agric Food Chem 2016 Sep 19;64(38):7068-75. Epub 2016 Sep 19.

Faculty of Life Sciences, Albrecht Daniel Thaer - Institute of Agricultural and Horticultural Sciences, Division Biosystems Engineering, Humboldt-Universität zu Berlin , Albrecht-Thaer-Weg 3, 14195 Berlin, Germany.

Effects of organic waste from a hydroponic system added with minerals (organomineral fertilizer) and synthetic fertilizer on major polyphenols of red oak leaf lettuce using HPLC-DAD-ESI-MS(3) were investigated. Interestingly, contents of the main flavonoid glycosides and caffeic acid derivatives of lettuce treated with organomineral fertilizer were equal to those synthesized without soil additives. This was found although soil nutrient concentrations, including that of nitrogen, were much lower without additives. However, lettuce treated with synthetic fertilizer showed a significant decrease in contents of caffeic acid derivatives and flavonoid glycosides up to 78.3 and 54.2%, respectively. It is assumed that a negative effect of a high yield on polyphenols as described in the growth-differentiation balance hypothesis can be counteracted by (i) a higher concentration of Mg or (ii) optimal physical properties of the soil structure. Finally, the organomineral substrate waste reused as fertilizer and soil improver resulted in the highest yield (+78.7%), a total fertilizer saving of 322 kg ha(-1) and waste reduction in greenhouses.
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http://dx.doi.org/10.1021/acs.jafc.6b02328DOI Listing
September 2016

Cascades of Regression Tree Fields for Image Restoration.

IEEE Trans Pattern Anal Mach Intell 2016 Apr;38(4):677-89

Conditional random fields (CRFs) are popular discriminative models for computer vision and have been successfully applied in the domain of image restoration, especially to image denoising. For image deblurring, however, discriminative approaches have been mostly lacking. We posit two reasons for this: First, the blur kernel is often only known at test time, requiring any discriminative approach to cope with considerable variability. Second, given this variability it is quite difficult to construct suitable features for discriminative prediction. To address these challenges we first show a connection between common half-quadratic inference for generative image priors and Gaussian CRFs. Based on this analysis, we then propose a cascade model for image restoration that consists of a Gaussian CRF at each stage. Each stage of our cascade is semi-parametric, i.e., it depends on the instance-specific parameters of the restoration problem, such as the blur kernel. We train our model by loss minimization with synthetically generated training data. Our experiments show that when applied to non-blind image deblurring, the proposed approach is efficient and yields state-of-the-art restoration quality on images corrupted with synthetic and real blur. Moreover, we demonstrate its suitability for image denoising, where we achieve competitive results for grayscale and color images.
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http://dx.doi.org/10.1109/TPAMI.2015.2441053DOI Listing
April 2016

Impact of fast-track concept elements in the classical pancreatic head resection (Kausch-Whipple procedure).

Pol Przegl Chir 2012 Aug;84(8):390-8

Institute for Quality Assurance in Medicine, Magdeburg, University Hospital, Magdeburg.

Unlabelled: The aim of the study was to determine statistically significant factors with an impact on the early postoperative surgical outcome.

Material And Methods: The influence of applied fast-track components on surgical results and early postoperative outcome in 143 consecutive Kausch-Whipple procedure patients was evaluated in a single-center retrospective analysis of a prospective collection of patient-associated pre-, peri- and postoperative data from 1997-2006.

Results: The in-hospital mortality rate was 2.8% (n=4). Fast-track measures were shown to have no effect on the morbidity rate in the multi-variate analysis. Over the study period, a decrease of intraoperative infusion volume from 14.2 mL/kg body weight/h in the first year to 10.7 mL/kg body weight/h in the last year was accompanied by an increase in patients requiring intraoperative catecholamines, up from 17% to 95%. The administration of ropivacain/sufentanil via thoracic peri-dural catheter injection initiated in 2000 and now considered the leading analgesic method, was used in 95% of the cases in 2006. Early extubation rate rose from 16.6% to 57.9%.

Conclusions: Fast-track aspects in the perioperative management have become more important in several surgical procedure even in those with a greater invasiveness such as Kausch-Whipple. However, such techniques used in peri-operative management of Kausch-Whipple pancreatic-head resections had no impact on the morbidity rate. In addition, the low in-hospital mortality rate was particularly attributed to surgical competence.
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http://dx.doi.org/10.2478/v10035-012-0066-4DOI Listing
August 2012

Early survival of comatose patients after severe traumatic brain injury with the dual cannabinoid CB1/CB2 receptor agonist KN38-7271: a randomized, double-blind, placebo-controlled phase II trial.

J Neurol Surg A Cent Eur Neurosurg 2012 Aug 13;73(4):204-16. Epub 2012 Jun 13.

Klinik für Neurochirurgie, Universitätsklinikum, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.

Unlabelled: BACKGROUND AND STUDY OBJECT: Despite many drug trials, no substance has yet been identified that improves the outcome of severe head injury. The dual cannabinoid CB1/CB2 receptor agonist KN38-7271 mediates potent neuroprotection in animal models. We describe here the first randomized, double-blind, prospective, placebo-controlled clinical phase IIa proof-of-concept trial to investigate the safety, pharmacokinetics, and potential efficacy of a cannabinoid receptor agonist in humans.

Patients And Methods: Out of the 439, 97 comatose patients at 14 European neurosurgical centers met the inclusion criteria. KN38-7271 was administered within 4.5 hours of the injury, and the patients received 1000, 500 μg, or placebo. The primary analysis was pharmacokinetic; efficacy was measured by survival and by neurological improvement or deterioration 7 and 14 days and 1, 3, and 6 months after the injury. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were analyzed from start of treatment to end of day 7.

Results: Survival rates within 1 month of the injury were significantly better in the treatment groups than in the placebo group (high-dose, Kaplan-Meier difference on day 30 + 0.12 with p = 0.043; low-dose, difference +0.15 with p = 0.011) but this effect was not seen after 6 months. Critical ICP and CPP were less extreme and less frequent in the treatment group. There were no severe and no serious adverse effects that could be attributed to KN38-7271.

Conclusions: KN38-7271 appeared beneficial in the acute early phase of the comatose patient after a head injury. Its use was safe and well tolerated by patients. These results may provide the basis for further phase II/III trials in larger study populations.
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http://dx.doi.org/10.1055/s-0032-1304815DOI Listing
August 2012

Endoscopic ultrasonography (EUS) in preoperative staging of gastric cancer--demand and reality.

Pol Przegl Chir 2012 Mar;84(3):152-7

Institute for Quality Control, University Hospital, Magdeburg Department of Surgery, Municipal Hospital-HELIOS, Plauen, Germany.

Unlabelled: Exact pretherapeutic staging is considered to be essential for decision-making in the therapeutic algorithm of gastric cancer. THE AIM OF THE STUDY was to characterize the role and value of EUS in the diagnostic and therapeutic management of gastric cancer in daily surgical practice.

Material And Methods: Thousand one hundred thirty nine patients with primary gastric cancer from 80 hospitals of each profile of care were enrolled in this systematic clinical prospective multicenter observational study over a time period of 12 months. The characteristics of the diagnostic management, in particular, of EUS were documented. The preoperative EUS findings were compared with the T stage (T1 to T4) and the N category (N+ or N-) revealed by the histopathologic investigation of the surgical specimen. By the mean of χ² test, the impact of EUS on the therapeutic decision-making was determined.

Results: Pretherapeutic EUS was only performed in 27.4% (n=312) of all patients. Overall, the diagnostic accuracy for the T stage was 42.6% in average. The subgroup analysis showed the following results: T1, 31.5%; T2, 42.6%; T3, 65.2%; T4, 17.6%. The correct predictive value of the N category was 71.3% reaching a sensitivity of 69.7% and a specificity of 73.3%. Overstaging was observed in 45.8%, understaging in only 10.8%. Additional diagnostic information by EUS was only provided in 4.7% of subjects.

Conclusions: The present study indicates the variability, limited reliability and only moderate acceptance of EUS in diagnosing gastric cancer in daily practice. In particular, the prediction of the T stage does not reach the data reported in the literature, which were mostly achieved in specific EUS studies.
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http://dx.doi.org/10.2478/v10035-012-0024-1DOI Listing
March 2012

Prognostic factors assessed for 15,096 patients with colon cancer in stages I and II.

World J Surg 2012 Jul;36(7):1693-8

Department of General, Visceral and Vascular Surgery, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.

Background: We focused on the risk factors for poor outcome after curative resection of a colon cancer in UICC stages I and II based on the data of the Germany-wide quality assurance study "colon/rectum cancer (primary tumor)." In some countries, all stage II colon cancer patients are encouraged to participate in a clinical trial. We feel that this approach is too broad.

Methods: Using the data of 15,096 patients operated on from January 1, 2000 to December 31, 2004, the following factors were analyzed with the Cox regression model: age, comorbidities, ASA score, gender, localization of the tumor (left colon vs. right colon), perioperative complications (yes/no), pT stage, grading (G1/G2 vs. G3/G4), L-status (lymph vessels invasion yes/no), and V-status (venous invasion yes/no).

Results: The probability of a local relapse in stages I and II was 1.5 and 4.6%, respectively, or distant metastases 4.7 and 10.2%, respectively. Only pT stage [hazard ratio (HR) for pT1 = 1, pT2 = 1.821, pT3 = 2.735, and pT4 = 5.881], L-status (HR for L1 = 1.393), age (HR per year = 1.021), as well as ASA score IV (HR = 4.536) had significant influence on tumor-free survival.

Conclusions: Despite favorable prognosis and R0 resection, a small percentage of patients will still relapse. The most important risk factor comprising the tumor-free survival is the pT stage followed by L-status and age. These results should be taken into consideration when determining the course for adjuvant chemotherapy, especially if the course includes the recommendation of clinical trial participation for stage II colon cancer patients after an R0 resection.
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http://dx.doi.org/10.1007/s00268-012-1531-2DOI Listing
July 2012

Determination of the therapeutic time window for human umbilical cord blood mononuclear cell transplantation following experimental stroke in rats.

Cell Transplant 2012 13;21(6):1199-211. Epub 2011 Dec 13.

Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.

Experimental treatment strategies using human umbilical cord blood mononuclear cells (hUCB MNCs) represent a promising option for alternative stroke therapies. An important point for clinical translation of such treatment approaches is knowledge on the therapeutic time window. Although expected to be wider than for thrombolysis, the exact time window for hUCB MNC therapy is not known. Our study aimed to determine the time window of intravenous hUCB MNC administration after middle cerebral artery occlusion (MCAO). Male spontaneously hypertensive rats underwent MCAO and were randomly assigned to hUCB MNC administration at 4, 24, 72, and 120 or 14 days. Influence of cell treatment was observed by magnetic resonance imaging on days 1, 8, and 29 following MCAO and by assessment of functional neurological recovery. On day 30, brains were screened for glial scar development and presence of hUCB MNCs. Further, influence of hUCB MNCs on necrosis and apoptosis in postischemic neural tissue was investigated in hippocampal slices cultures. Transplantation within a 72-h time window resulted in an early improvement of functional recovery, paralleled by a reduction of brain atrophy and diminished glial scarring. Cell transplantation 120 h post-MCAO only induced minor functional recovery without changes in the brain atrophy rate and glial reactivity. Later transplantation (14 days) did not show any benefit. No evidence for intracerebrally localized hUCB MNCs was found in any treatment group. In vitro hUCB MNCs were able to significantly reduce postischemic neural necrosis and apoptosis. Our results for the first time indicate a time window of therapeutic hUCB MNC application of at least 72 h. The time window is limited, but wider than compared to conventional pharmacological approaches. The data furthermore confirms that differentiation and integration of administered cells is not a prerequisite for poststroke functional improvement and lesion size reduction.
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http://dx.doi.org/10.3727/096368911X589609DOI Listing
May 2013

Neonatal freshwater drowning after birth in the bathroom.

Am J Forensic Med Pathol 2011 Jun;32(2):119-23

Department of Legal Medicine, Technical University, Dresden, Germany.

The macroscopic and microscopic findings in neonatal freshwater drowning are demonstrated on the basis of 3 exemplary cases of birth in the bathroom after concealed pregnancy. If the newborn is expelled under water and remains there until death, the lungs cannot be ventilated with air. In case of incomplete or only temporary submersion, aeration of the lungs may develop in the immediate postpartum period. The morphologic criteria of separate existence are critically discussed with respect to the presented findings.
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http://dx.doi.org/10.1097/PAF.0b013e318187dff9DOI Listing
June 2011

Risk adjustment as basis for rational benchmarking: the example of colon carcinoma.

World J Surg 2011 Jan;35(1):196-205

Klinik für Chirurgie, Carl-Thiem-Klinikum Cottbus, Thiemstr. 111, 03048, Cottbus, Germany.

Background: The results of resection of colorectal carcinoma can vary greatly from one hospital to another. However, this does not necessarily reflect differences in the quality of treatment. The purpose of this study was to compare various tools for the risk-adjusted assessment of treatment results after resection of colorectal carcinoma within the context of hospital benchmarking.

Methods: On the basis of a data pool provided by a multicentric observation study of patients with colon cancer, the postoperative in-hospital mortality rates at two high-volume hospitals ("A" and "B") were compared. After univariate comparison, risk-adjusted comparison of postoperative mortality was performed by logistic regression analysis (LReA), propensity-score analysis (PScA), and the CR-POSSUM score. Postoperative complications were compared by LReA and PScA.

Results: Although postoperative mortality differed significantly (P = 0.041) in univariate comparison of hospitals A and B (2.9% vs. 6.4%), no significant difference was found by LReA or PScA. Similarly, the observed mortality at these did not differ significantly from the mortality estimated by the CR-POSSUM score (hospital A, 2.9%/4.9%, P = 0.298; hospital B, 6.4%/6.5%, P = 1.000). Significant differences were seen in risk-adjusted comparison of most postoperative complications (by both LReA and PScA), but there were no differences in the rates of relaparotomy or anastomotic leakage that required surgery.

Conclusions: For the hard outcome variable "postoperative mortality," none of the three risk adjustment procedures showed any difference between the hospitals. The CR-POSSUM score can be regarded as the most practicable tool for risk-adjusted comparison of the outcome of colon-carcinoma resection in clinical benchmarking.
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http://dx.doi.org/10.1007/s00268-010-0796-6DOI Listing
January 2011

The protein tyrosine kinase Tec regulates a CD44highCD62L- Th17 subset.

J Immunol 2010 Nov 24;185(9):5111-9. Epub 2010 Sep 24.

Division of Immunobiology, Institute of Immunology, Medical University of Vienna, Vienna, Austria.

The generation of Th17 cells has to be tightly controlled during an immune response. In this study, we report an increase in a CD44(high)CD62L(-) Th17 subset in mice deficient for the protein tyrosine kinase Tec. CD44(high)CD62L(-) Tec(-/-) CD4(+) T cells produced enhanced IL-17 upon activation, showed increased expression levels of IL-23R and RORγt, and IL-23-mediated expansion of Tec(-/-) CD4(+) T cells led to an increased production of IL-17. Tec(-/-) mice immunized with heat-killed Streptococcus pneumoniae displayed increased IL-17 expression levels in the lung postinfection with S. pneumoniae, and this correlated with enhanced pneumococcal clearance and reduced lung inflammation compared with Tec(+/+) mice. Moreover, naive Tec(-/-) OT-II CD4(+) T cells produced higher levels of IL-17 when cultured with OVA peptide-loaded bone marrow-derived dendritic cells that have been previously activated with heat-killed S. pneumoniae. Taken together, our data indicated a critical role for Tec in T cell-intrinsic signaling pathways that regulate the in vivo generation of CD44(high)CD62L(-) effector/memory Th17 populations.
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http://dx.doi.org/10.4049/jimmunol.1001734DOI Listing
November 2010
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