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1.
Pathologie (Heidelb) ; 44(6): 348-356, 2023 Nov.
Article in German | MEDLINE | ID: mdl-37828376

ABSTRACT

Osseous lesions are rare; however, their incidence is increased in childhood and adolescence. The spectrum of osseous processes in this age group is limited, with benign lesions being much more prevalent than malignant tumors. For the differential diagnosis, it is essential to have in-depth knowledge of the more frequent bone diseases in children and adolescents. The current review presents these diseases based on the morphologic approach of the WHO classification, including giant cell-rich and cystic lesions, chondrogenic and bone-forming lesions [7]. Small round cell sarcomas which are now summarized in a separate chapter of the WHO classification have been described previously [12, 20].


Subject(s)
Bone Neoplasms , Humans , Adolescent , Child , Bone Neoplasms/diagnosis , Giant Cells/pathology
2.
J Imaging ; 8(9)2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36135416

ABSTRACT

We study the performance of CLAIRE-a diffeomorphic multi-node, multi-GPU image-registration algorithm and software-in large-scale biomedical imaging applications with billions of voxels. At such resolutions, most existing software packages for diffeomorphic image registration are prohibitively expensive. As a result, practitioners first significantly downsample the original images and then register them using existing tools. Our main contribution is an extensive analysis of the impact of downsampling on registration performance. We study this impact by comparing full-resolution registrations obtained with CLAIRE to lower resolution registrations for synthetic and real-world imaging datasets. Our results suggest that registration at full resolution can yield a superior registration quality-but not always. For example, downsampling a synthetic image from 10243 to 2563 decreases the Dice coefficient from 92% to 79%. However, the differences are less pronounced for noisy or low contrast high resolution images. CLAIRE allows us not only to register images of clinically relevant size in a few seconds but also to register images at unprecedented resolution in reasonable time. The highest resolution considered are CLARITY images of size 2816×3016×1162. To the best of our knowledge, this is the first study on image registration quality at such resolutions.

3.
BMC Infect Dis ; 22(1): 696, 2022 Aug 17.
Article in English | MEDLINE | ID: mdl-35978295

ABSTRACT

BACKGROUND: Capnocytophaga canimorsus, a Gram-negative rod, belongs to the Flavobacteriaceae family and colonizes the oropharynx of dogs and cats. Infections with C. canimorsus are rare and can induce a systemic infection with a severe course of the disease. So far, only five case reports of C. canimorsus infections associated with Waterhouse-Friderichsen Syndrome (WFS) have been reported with only two of the patients having a history of splenectomy. CASE PRESENTATION: Here, we report a fatal case of WFS due to C. canimorsus bacteremia and mycetal superinfection in a 61-year-old female asplenic patient. Despite extensive therapy including mechanical ventilation, antibiotic coverage with meropenem, systemic corticosteroids medication, vasopressor therapy, continuous renal replacement therapy, therapeutic plasma exchange, multiple transfusions of blood products and implantation of a veno-arterial extracorporeal membrane oxygenation the patient died 10 days after a dog bite. The autopsy showed bilateral hemorrhagic necrosis of the adrenal cortex and septic embolism to heart, kidneys, and liver. Diagnosis of C. canimorsus was prolonged due to the fastidious growth of the bacteria. CONCLUSIONS: The occurrence of a severe sepsis after dog bite should always urge the attending physician to consider C. canimorsus as the disease-causing pathogen. A therapeutic regimen covering C. canimorsus such as aminopenicillins or carbapenems should be chosen. However, despite maximum therapy, the prognosis of C. canimorsus-induced septic shock remains very poor. Asplenic or otherwise immunocompromised patients are at higher risk for a severe course of disease and should avoid exposure to dogs and cats and consider antibiotic prophylaxis after animal bite.


Subject(s)
Bites and Stings , Cat Diseases , Dog Diseases , Gram-Negative Bacterial Infections , Sepsis , Waterhouse-Friderichsen Syndrome , Animals , Bites and Stings/complications , Capnocytophaga , Cats , Dog Diseases/diagnosis , Dog Diseases/therapy , Dogs , Female , Gram-Negative Bacterial Infections/microbiology , Sepsis/diagnosis , Waterhouse-Friderichsen Syndrome/complications
4.
Medicina (Kaunas) ; 58(7)2022 Jul 19.
Article in English | MEDLINE | ID: mdl-35888670

ABSTRACT

Epithelioid rhabdomyosarcoma is a rare condition, which may be clinically misinterpreted as melanoma due to its morphological appearance. Careful morphological and immunohistochemical analysis play an important role in its diagnosis. This case report describes the clinicopathological features of an epithelioid RMS diagnosed at the high parietal area of the head. A 71-year-old male patient presented a red-brown pigmented ulcerative nodule in the high parietal region of the head. Previous biopsy and computer tomography imaging revealed a malignant melanoma in stage I (pT2, sN0, Mx). After tumor operation, histological and immunohistochemical analysis of the tumor were conducted. Histological analysis showed an erosive lesion with a monomorphic cell population containing small cells with prominent nucleoli. A positivity was confirmed for CD10, Vimentin, and Desmin. MyoD1 was detected, as well as a fluctuating signal for p53. Molecular analysis revealed a negativity for Sox-10, and a weak positivity for CK8/18 by absence of p40. Based on the morphological and immunohistochemical findings, the tumor was diagnosed as epithelioid RMS.


Subject(s)
Melanoma , Rhabdomyosarcoma, Embryonal , Rhabdomyosarcoma , Skin Neoplasms , Aged , Biomarkers, Tumor/analysis , Humans , Male , Rhabdomyosarcoma/chemistry , Rhabdomyosarcoma/diagnosis , Rhabdomyosarcoma/pathology , Skin Neoplasms/pathology
5.
Cell Oncol (Dordr) ; 45(3): 399-413, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35556229

ABSTRACT

PURPOSE: Synovial sarcoma (SySa) is a rare soft tissue tumor characterized by a reciprocal t(X;18) translocation. The chimeric SS18-SSX fusion protein represents the major driver of the disease, acting as aberrant transcriptional dysregulator. Oncogenic mechanisms whereby SS18-SSX mediates sarcomagenesis are incompletely understood, and strategies to selectively target SySa cells remain elusive. Based on results of Phospho-Kinase screening arrays, we here investigate the functional and therapeutic relevance of the transcription factor CREB in SySa tumorigenesis. METHODS: Immunohistochemistry of phosphorylated CREB and its downstream targets (Rb, Cyclin D1, PCNA, Bcl-xL and Bcl-2) was performed in a large cohort of SySa. Functional aspects of CREB activity, including SS18-SSX driven circuits involved in CREB activation, were analyzed in vitro employing five SySa cell lines and a mesenchymal stem cell model. CREB mediated transcriptional activity was modulated by RNAi-mediated knockdown and small molecule inhibitors (666-15, KG-501, NASTRp and Ro 31-8220). Anti-proliferative effects of the CREB inhibitor 666-15 were tested in SySa avian chorioallantoic membrane and murine xenograft models in vivo. RESULTS: We show that CREB is phosphorylated and activated in SySa, accompanied by downstream target expression. Human mesenchymal stem cells engineered to express SS18-SSX promote CREB expression and phosphorylation. Conversely, RNAi-mediated knockdown of SS18-SSX impairs CREB phosphorylation in SySa cells. Inhibition of CREB activity reduces downstream target expression, accompanied by suppression of SySa cell proliferation and induction of apoptosis in vitro and in vivo. CONCLUSION: In conclusion, our data underline an essential role of CREB in SySa tumorigenesis and provides evidence for molecular targeted therapies.


Subject(s)
Sarcoma, Synovial , Animals , Apoptosis , Carcinogenesis , Cell Line, Tumor , Humans , Mice , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Sarcoma, Synovial/drug therapy , Sarcoma, Synovial/genetics , Sarcoma, Synovial/metabolism
6.
Open Res Eur ; 2: 51, 2022.
Article in English | MEDLINE | ID: mdl-37645328

ABSTRACT

preCICE is a free/open-source coupling library. It enables creating partitioned multi-physics simulations by gluing together separate software packages. This paper summarizes the development efforts in preCICE of the past five years. During this time span, we have turned the software from a working prototype -- sophisticated numerical coupling methods and scalability on ten thousands of compute cores -- to a sustainable and user-friendly software project with a steadily-growing community. Today, we know through forum discussions, conferences, workshops, and publications of more than 100 research groups using preCICE. We cover the fundamentals of the software alongside a performance and accuracy analysis of different data mapping methods. Afterwards, we describe ready-to-use integration with widely-used external simulation software packages, tests, and continuous integration from unit to system level, and community building measures, drawing an overview of the current preCICE ecosystem.

7.
Materials (Basel) ; 14(15)2021 Jul 29.
Article in English | MEDLINE | ID: mdl-34361429

ABSTRACT

The effect of different constitutive modelling choices is crucial under a high strain rate as encountered in ballistic applications. Natural fragmentation of explosively driven cylinder rings is chosen as a simplified example to describe the ability of numerical simulations to describe fractures. The main research interests are the importance of (i) material imperfections, (ii) the accuracy of fracture models vs. damage models, (iii) the plasticity algorithm (stress update), (iv) the introduction of a triaxiality cutoff criterion to the damage models, and (v) different constitutive models (plasticity and damage). Due to the complexity of the propagation and coalescense of multiple cracks in classical methods, smoothed-particle hydrodynamics (SPH) is used as a tailor-made method to discretise the model. An elasto-plasticity model, a damage model and an equation of state describe the material behaviour. The required material parameters are determined based on stress-strain curves from quasi-static and dynamic tests. The Johnson-Cook model, with and without a modification of the strain rate term, and the Rusinek-Klepaczko model are used to describe plasticity. These plasticity models are combined either with the Johnson-Cook, the Lemaitre, or the Dolinski-Rittel damage model and the Mie-Grüneisen equation of state. The numerical results show that (i) a random distribution of initial damage increases irregularity of cracks, and gives more realistic fragment shapes, (ii) a coupling of plasticity model and fracture criterion has only a small effect on the fracture behaviour, (iii) using an iterative plasticity solver has a positive effect on the fracture behaviour, although this effect is marginal, (iv) adding a triaxiality cutoff criterion to the damage models improves the predicted fragment masses in the numerical simulations significantly, and (v) good accordance between experiments and numerical simulations are found for the Dolinski-Rittel and Lemaitre damage model with both plasticity models.

8.
HSS J ; 7(3): 235-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-23024619

ABSTRACT

BACKGROUND: It is widely believed that a deep implant infection leads to poor functional and emotional outcomes following total hip arthroplasty. QUESTIONS/PURPOSE: The purpose of this retrospective comparative review was to determine if patients who undergo two-stage, septic revision hip arthroplasty will have decreased emotional and general health scores, in addition to decreased function, compared to the aseptic revision group. PATIENTS AND METHODS: One hundred forty-five of 195 patients who underwent aseptic total hip revision for aseptic loosening (mean follow-up = 61 months) and 45 of 73 patients who underwent two-stage, septic revision hip arthroplasty (mean follow-up = 48 months) met the inclusion criteria and had a technically successful outcome. All patients were retrospectively evaluated using Harris Hip Scores (HHS), ad hoc questions, and the SF-36 Health Survey. RESULTS: The average HHS were 73.2 ± 20.5 (aseptic) and 57.4 ± 20.6 (septic). Significant differences in the SF-36 Health Survey were found between the two groups in: physical functioning (p = 0.026) and role limitations due to physical health (p = 0.004). No significant difference in SF-36 scores was seen in: Energy/Fatigue, General Health Perception, Personal or Emotional Problems, Role Limitations due to Emotional Well Being, Social Functioning, and Bodily Pain. CONCLUSIONS: Two-stage, septic revision produces a poor functional outcome compared to aseptic revision; however, the overall impact of a septic revision emotionally and socially was not significantly different than patients undergoing aseptic revision.

9.
J Am Chem Soc ; 132(29): 10107-17, 2010 Jul 28.
Article in English | MEDLINE | ID: mdl-20590116

ABSTRACT

Ethynylene and p-phenylene are frequently employed constitutional units in constructing the backbone of nanoscopic molecules with specific shape and mechanical or electronic function. How well these properties are defined depends on the flexibility of the backbone, which can be characterized via the end-to-end distance distribution. This distribution is accessible by pulse electron paramagnetic resonance (EPR) distance measurements between spin labels that are attached at the backbone. Four sets of oligomers with different sequences of p-phenylene and ethynylene units and different spin labels were prepared using polar tagging as a tool for simple isolation of the targeted compounds. By variation of backbone length, of the sequence of p-phenylene and ethynylene units, and of the spin labels a consistent coarse-grained model for backbone flexibility of oligo(p-phenyleneethynylene)s and oligo(p-phenylenebutadiynylene)s is obtained. The relation of this harmonic segmented chain model to the worm-like chain model for shape-persistent polymers and to atomistic molecular dynamics simulations is discussed. Oligo(p-phenylenebutadiynylene)s are found to be more flexible than oligo(p-phenyleneethynylene)s, but only slightly so. The end-to-end distance distribution measured in a glassy state of the solvent at a temperature of 50 K is found to depend on the glass transition temperature of the solvent. In the range between 91 and 373 K this dependence is in quantitative agreement with expectations for flexibility due to harmonic bending. For the persistence lengths at 298 K our data predict values of (13.8 +/- 1.5) nm for poly(p-phenyleneethynylene)s and of (11.8 +/- 1.5) nm for poly(p-phenylenebutadiynylene)s.


Subject(s)
Alkynes/chemistry , Benzene/chemistry , Models, Chemical , Polymers/chemistry , Electron Spin Resonance Spectroscopy
10.
Beilstein J Org Chem ; 6: 57, 2010 Jun 01.
Article in English | MEDLINE | ID: mdl-20625532

ABSTRACT

One important access to monodisperse (functionalized) oligoPPEs is based on the orthogonality of the alkyne protecting groups triisopropylsilyl and hydroxymethyl (HOM) and on the polar tagging with the hydroxymethyl moiety for an easy chromatographic separation of the products. This paper provides an update of this synthetic route. For the deprotection of HOM protected alkynes, γ-MnO2 proved to be better than (highly) activated MnO2. The use of HOM as an alkyne protecting group is accompanied by carbometalation as a side reaction in the alkynyl-aryl coupling. The extent of carbometalation can be distinctly reduced through substitution of HOM for 1-hydroxyethyl. The strategy of polar tagging is extended by embedding ether linkages within the solubilising side chains. With building blocks such as 1,4-diiodo-2,5-bis(6-methoxyhexyl) less steps are needed to assemble oligoPPEs with functional end groups and the isolation of pure compounds becomes simple. For the preparation of 1,4-dialkyl-2,5-diiodobenzene a better procedure is presented together with the finding that 1,4-dialkyl-2,3-diiodobenzene, a constitutional isomer of 1,4-dialkyl-2,5-diiodobenzene, is one of the byproducts.

11.
J Org Chem ; 74(20): 7733-42, 2009 Oct 16.
Article in English | MEDLINE | ID: mdl-19761236

ABSTRACT

The synthesis of monodisperse oligo(p-phenyleneethynylene)s 8a(n) with alternating 2,5-dihexyl-1,4-phenylene and 6,14-di-tert-butyl-1,4-triptycylene units and orthogonally protected alkyne end groups is reported. Starting from 6,14-di-tert-butyl-1-(2-triisopropylsilylethynyl)-4-(2-trimethylsilylethynyl)triptycene (5a), 1,4-dihexyl-2,5-diiodobenzene (10), and 1,4-dihexyl-2-iodo-5-(3-hydroxyprop-1-ynyl)benzene (9), oligomers with up to four repeating units, i.e., eight phenyleneethynylene units, were prepared through a partially divergent-convergent route with the alkynyl-aryl (Sonogashira-Hagihara) coupling as the key reaction. The starting compound 5a was prepared from triptycenequinone through a sequence of addition of 2-trialkylsilylethynyllithium, reduction and concomitant elimination of water, conversion of the phenol into a triflate, and finally Pd/Cu-catalyzed coupling with trialkylsilylethyne. A similar access to the key compound for a stringent divergent-convergent route, 6,14-di-tert-butyl-1-(3-hydroxybut-1-ynyl)-4-(2-triisopropylsilylethynyl)triptycene (6), is reported. The optical properties of the oligomers 8a(n) and the corresponding oligo(2,5-dihexyl-1,4-phenyleneethynylene)s in dilute solution are almost identical, whereas they differ significantly for the solid, undiluted compounds.

12.
Phys Chem Chem Phys ; 11(31): 6580-91, 2009 Aug 21.
Article in English | MEDLINE | ID: mdl-19639133

ABSTRACT

Distance measurements by pulse electron paramagnetic resonance techniques are increasingly applied to systems that contain more than two spin labels. Under typical experimental conditions this leads to signal contributions from sum and difference combinations of dipolar frequencies. As these contributions are neglected in the expressions used in data analysis they cause artifacts in distance distributions. It is shown that the artifacts lead to substantial broadening of the distance distribution. By measuring double electron-electron resonance (DEER) data with variable inversion efficiency of the pump pulse and fitting the data at each point in time by appropriate polynomials the pair contribution can be separated from the three-spin contribution. Experiments on a conformationally invariant triradical with equilateral triangle geometry and the corresponding biradical with the same interspin distance demonstrate that this approach leads to a considerable improvement in the distance distribution. The three-spin contribution is shown to provide information on angles between spin-spin vectors. Data for a series of triradicals with equilateral, isosceles, and scalene triangle geometry are analysed by fitting a general triangle model simultaneously to the dipolar spectra of the pair and three-spin contribution. The agreement with the expected side lengths of the triangles is satisfying.


Subject(s)
Electron Spin Resonance Spectroscopy/methods , Electrons , Microwaves , Molecular Structure , Spin Labels
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