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2. Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma

Author

Rauch, P., Stefanits, H., Aichholzer, M., Serra, C., Vorhauer, D., Wagner, H., Böhm, P., Hartl, S., Manakov, I., Sonnberger, M., Buckwar, E., Ruiz-Navarro, F., Heil, K., Glöckel, M., Oberndorfer, J., Spiegl-Kreinecker, S., Aufschnaiter-Hiessböck, K., Weis, S., Leibetseder, A., Thomae, W., Hauser, T., Auer, C., Katletz, S., Gruber, A., and Gmeiner, M.

Published
2023
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10. Scientific Reports / Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma

Author

Rauch, Philipp, Stefanits, Harald, Aichholzer, Martin, Serra, C., Vorhauer, D., Wagner, H., Böhm, P., Hartl, S., Manakov, I., Sonnberger, M., Buckwar, E., Ruiz-Navarro, F., Heil, K., Glöckel, M., Oberndorfer, J., Spiegl-Kreinecker, S., Aufschnaiter-Hiessböck, K., Weis, S., Leibetseder, A., Thomae, W., Hauser, T., Auer, C., Katletz, S., Gruber, Andreas, and Gmeiner, N.

Subjects
CNS cancer, Network models
Abstract

Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79–0.86) for the training cohort over 10 years and 0.74 (Cl 0.64–0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73–0.82) for training and 0.67 (Cl 0.57–0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate. Version of record

Published
2023

15. Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression

Author

Haybaeck J, Postruznik M, Miller CL, Dulay JR, Llenos IC, and Weis S

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Johannes Haybaeck,1 Magdalena Postruznik,1 Christine L Miller,2 Jeannette R Dulay,3 Ida C Llenos,3,4 Serge Weis3,4 1Department of Neuropathology, Institute of Pathology, Medical University Graz, Graz, Austria; 2Department of Pediatrics, Johns Hopkins University, Baltimore, 3Laboratory of Brain Research and Neuropathology, Departments of Psychiatry and Pathology, Uniformed Services University of the Health Sciences, and Stanley Medical Research Institute, Bethesda, MD, USA; 4Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria Background: Retinoids regulate gene expression in different cells and tissues at the transcriptional level. Retinoic acid transcriptionally regulates downstream regulatory molecules, including enzymes, transcription factors, cytokines, and cytokine receptors. Animal models indicate an involvement of retinoid signaling pathways in the regulation of synaptic plasticity and learning, especially in the hippocampus. Retinoic acid-inducible or induced gene 1 (RAI-1) is induced during neuronal differentiation, and was associated with the severity of the phenotype and response to medication in schizophrenic patients. Methods: In the present study, we used immunohistochemistry to investigate the expression of RAI-1 in 60 brains from the Stanley Neuropathology Consortium (15 cases each from controls and from patients with schizophrenia, bipolar disorder, and major depression). Rating scores for density and intensity were determined in the dorsolateral prefrontal cortex. Results: All four groups showed high interindividual variation. RAI-1-positive cells were identified as neurons and astrocytes. Significantly increased intensities in cortical neurons were noted in all three major psychiatric groups compared with controls. The density of RAI-1-positive neurons was increased (P=0.06) in schizophrenia and bipolar disorder. In bipolar disorder, RAI-1-positive astrocytes in gray matter showed a significantly increased intensity and compound value. Thus, a significant increase in the parameters measured was found in schizophrenia, bipolar disorder, and major depression. Conclusion: Our study shows a significant increase in expression of RAI-1 in the brains from patients with schizophrenia, bipolar disorder, or major depression. The increased expression might reflect altered signaling pathways, like that for retinoic acid. The underlying mechanisms leading to the increased expression and its functional consequences are so far unknown, and remain to be investigated in future studies. Keywords: retinoic acid-inducible gene 1, dorsolateral prefrontal cortex, schizophrenia, bipolar disorder, major depression

Published
2015

21. Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge

Author

Winkler, M.S. Skirecki, T. Brunkhorst, F.M. Cajander, S. Cavaillon, J.-M. Ferrer, R. Flohé, S.B. García-Salido, A. Giamarellos-Bourboulis, E.J. Girardis, M. Kox, M. Lachmann, G. Martin-Loeches, I. Netea, M.G. Spinetti, T. Schefold, J.C. Torres, A. Uhle, F. Venet, F. Weis, S. Scherag, A. Rubio, I. Osuchowski, M.F.

Abstract

Many milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered on clinical studies. However, several animal SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting clinical evidence rapidly emerge. In this review, we characterize the existing animal models exposing their relevance and limitations as well as outline their utility in COVID-19 drug and vaccine development. Concurrently, we summarize the status of clinical trial research and discuss the novel tactics utilized in the largest multi-center trials aiming to accelerate generation of reliable results that may subsequently shape COVID-19 clinical treatment practices. We also highlight areas of improvement for animal studies in order to elevate their translational utility. In pandemics, to optimize the use of strained resources in a short time-frame, optimizing and strengthening the synergy between the preclinical and clinical domains is pivotal. © 2021 The Authors

Published
2021

22. Host cystathionine-γ lyase derived hydrogen sulfide protects against Pseudomonas aeruginosa sepsis

Author

Renieris, G. Droggiti, D.-E. Katrini, K. Koufargyris, P. Gkavogianni, T. Karakike, E. Antonakos, N. Damoraki, G. Karageorgos, A. Sabracos, L. Katsouda, A. Jentho, E. Weis, S. Wang, R. Bauer, M. Szabo, C. Platoni, K. Kouloulias, V. Papapetropoulos, A. Giamarellos-Bourboulis, E.J.

Subjects
parasitic diseases, equipment and supplies
Abstract

Hydrogen sulfide (H2S) has recently been recognized as a novel gaseous transmitter with several anti-inflammatory properties. The role of host- derived H2S in infections by Pseudomonas aeruginosa was investigated in clinical and mouse models. H2S concentrations and survival was assessed in septic patients with lung infection. Animal experiments using a model of severe systemic multidrug-resistant P. aeruginosa infection were performed using mice with a constitutive knock-out of cystathionine-γ lyase (Cse) gene (Cse-/-) and wild-type mice with a physiological expression (Cse+/+). Experiments were repeated in mice after a) treatment with cyclophosphamide; b) bone marrow transplantation (BMT) from a Cse+/+ donor; c) treatment with H2S synthesis inhibitor aminooxyacetic acid (ΑΑΑ) or propargylglycine (PAG) and d) H2S donor sodium thiosulfate (STS) or GYY3147. Bacterial loads and myeloperoxidase activity were measured in tissue samples. The expression of quorum sensing genes (QS) was determined in vivo and in vitro. Cytokine concentration was measured in serum and incubated splenocytes. Patients survivors at day 28 had significantly higher serum H2S compared to non-survivors. A cut- off point of 5.3 μΜ discriminated survivors with sensitivity 92.3%. Mortality after 28 days was 30.9% and 93.7% in patients with H2S higher and less than 5.3 μΜ (p = 7 x 10−6). In mice expression of Cse and application of STS afforded protection against infection with multidrug-resistant P. aeruginosa. Cyclophosphamide pretreatment eliminated the survival benefit of Cse+/+ mice, whereas BMT increased the survival of Cse-/- mice. Cse-/- mice had increased pathogen loads compared to Cse+/+ mice. Phagocytic activity of leukocytes from Cse-/- mice was reduced but was restored after H2S supplementation. An H2S dependent down- regulation of quorum sensing genes of P.aeruginosa could be demonstrated in vivo and in vitro. Endogenous H2S is a potential independent parameter correlating with the outcome of P. aeruginosa. H2S provides resistance to infection by MDR bacterial pathogens. Copyright: © 2021 Renieris et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Published
2021

24. Quantum-coherent coupling of a mechanical oscillator to an optical cavity mode

Author

Verhagen, E., Deleglise, S., Weis, S., Schliesser, A., and Kippenberg, T.J.

Subjects
Optics -- Research, Quantum theory -- Research, Oscillators (Electronics) -- Mechanical properties -- Models, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Optical laser fields have been widely used to achieve quantum control over the motional and internal degrees of freedom of atoms and ions (1,2), molecules and atomic gases. A route to controlling the quantum states of macroscopic mechanical oscillators in a similar fashion is to exploit the parametric coupling between optical and mechanical degrees of freedom through radiation pressure in suitably engineered optical cavities (3-6). If the optomechanical coupling is 'quantum coherent'--that is, if the coherent coupling rate exceeds both the optical and the mechanical decoherence rate--quantum states are transferred from the optical field to the mechanical oscillator and vice versa. This transfer allows control of the mechanical oscillator state using the wide range of available quantum optical techniques. So far, however, quantum-coherent coupling of micromechanical oscillators has only been achieved using microwave fields at millikelvin temperatures (7,8). Optical experiments have not attained this regime owing to the large mechanical decoherence rates (9) and the difficulty of overcoming optical dissipation (10). Here we achieve quantum-coherent coupling between optical photons and a micromechanical oscillator. Simultaneously, coupling to the cold photon bath cools the mechanical oscillator to an average occupancy of 1.7 ± 0.1 motional quanta. Excitation with weak classical light pulses reveals the exchange of energy between the optical light field and the micromechanical oscillator in the time domain at the level of less than one quantum on average. This optomechanical system establishes an efficient quantum interface between mechanical oscillators and optical photons, which can provide decoherence-free transport of quantum states through optical fibres. Our results offer a route towards the use of mechanical oscillators as quantum transducers or in microwave-to-optical quantum links (11-15)., Mechanical oscillators are at the heart of many precision experiments and can exhibit exceptionally low dissipation. The possibility of controlling the quantum states of engineered micro- or nano-mechanical oscillators has [...]

Published
2012
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44. Multilayer chromium nitride/carbon coatings deposited by magnetron sputtering

Author

Sidelev, Dmitry Vladimirovich, Obrosov, A. V., and Weis, S.

Subjects
нитрид хрома, толщина, углерод, механические свойства, комбинационное рассеяние, рентгеновская дифракция, магнетронное распыление, многослойные покрытия, слои, структурные свойства
Published
2019

45. Identification of suitable controls for miRNA quantification in T-cells and whole blood cells in sepsis

Author

Hirschberger, S. Hübner, M. Strauß, G. Effinger, D. Bauer, M. Weis, S. Giamarellos-Bourboulis, E.J. Kreth, S.

Abstract

Complex immune dysregulation is a hallmark of sepsis. The occurring phases of immunosuppression and hyperinflammation require rapid detection and close monitoring. Reliable tools to monitor patient’s immune status are yet missing. Currently, microRNAs are being discussed as promising new biomarkers in sepsis. However, no suitable internal control for normalization of miRNA expression by qPCR has been validated so far, thus hampering their potential benefit. We here present the first evaluation of endogenous controls for miRNA analysis in human sepsis. Novel candidate reference miRNAs were identified via miRNA microArray. TaqMan qPCR assays were performed to evaluate these microRNAs in T-cells and whole blood cells of sepsis patients and healthy controls in two independent cohorts. In T-cells, U48 and miR-320 proved suitable as endogenous controls, while in whole blood cells, U44 and miR-942 provided best stability values for normalization of miRNA quantification. Commonly used snRNA U6 exhibited worst stability in all sample groups. The identified internal controls have been prospectively validated in independent cohorts. The critical importance of housekeeping gene selection is emphasized by exemplary quantification of imuno-miR-150 in sepsis patients. Use of appropriate internal controls could facilitate research on miRNA-based biomarker-use and might even improve treatment strategies in the future. © 2019, The Author(s).

Published
2019

48. Abstracts

Author

Rosemberg, S., Telxelra, M. J., Alves, V. A. F., Perry J. R., Ang L. C., Bilbao J. M., Muller P. J., Min, Kyung -Whan, Cashman, Robert, Brumback, Roger A., Rao, C., Deloso, D., Anderson, V., Seymour, A., Wrzolek, M., Abdu, A., Swanson, R., Honavar, M., Waters, K. B., Wise, S. M., Kubota, T., Sato, K., Kabuto, M., Nakagawa, T., Kitai, R., Nitta, H., Yamashita, J., Vital, C., Rivel, J., Sangalli, F., Benjelloun, B., Vital, A., Leger, F., Riemens, V., Epardeau, B., Guerin, J., Coindre, J. M., Ruchoux, M. M., Dhellemmes, P., Hamon, M., Lecomte, M., Hassoun, J., Yagishita, Saburo, Kawano, Nobuyuki, Kameya, Toru, Bowman, R., Liwnicz, B. H., Peckham, N., Barbosa-Coutinho, L. M., Hilbig, L. M., Hilbig, A., Loiseau, H., Mouton, L., Delisle, H. B., Rummens, C., Akai, F., Taneda, M., Iwasaki, H., Suzuki, Y., Tsanaclis, A. M. C., Aguiar, P. H. P., Logullo, A. F., Matamores, M. R., Yacubian, A., Komatsu, H., Oka, H., Suwa, T., Stoltenburg-Didinger, G., Gotzia, C., Benndorf, G., Kepes, J. J., Baba-Ahmed, R., Wong, K., Raisanen, J., Taylor, S. L., McDermott, M. W., Gutin, P., Havlioglu, Necat, Manepalli, Anantha, Galindo, Lorenzo, Sotelo-Avila, Cirilo, Grosso, Leonard, Kavavattathayyil, S., Chen, P., Wrzolek, M. A., Cook, J., Woodward, D. E., Tracqui, P., Cruywagen, G. C., Murray, J. D., Bartoo, G. T., Alvord, Jr., E. C., Szymas, Janusz, Jelonek, Jacek, Krawiec, Krzysztof, Slowinski, Roman, Coons, S. W., Johnson, P. C., Uro, E., Bousquet, P. H., Delisle, M. B., Rangueil, C. H. U., Torp, S. H., Johannesen, E., Lindboe, C. F., Beil, Michael, Kato, S., Morita, T., Kato, M., Herz, F., Hirano, A., Ohama, E., Albuquerque, L., Pimentel, J., Távora, L., Antunes, N. L., Weis, S., Protopapa, D., Mäerz, U., Winkler, P. A., Reulen, H. J., Mehraein, P., Di, Xiao, Reifenberger, Julia, Reifenberger, Guido, Liu, Lu, James, C. David, Wechsler, Wolfgang, Collins, V. Peter, McLendon, R. E., Batra, S. K., Friedman, H. S., Rasheed, B. K. A., Bigner, D. D., Bigner, S. K., Patt, S., Thiel, G., Labrousse, F., de Néchaud, B., Gomès, D., Daumas-Duport, C., Allarmargot, C., Dupouey, P., Vrionis, F., Qi, P., Cherington, V., Cano, G., Wu, J., Lampson, L. A., Chen, A., Vortmeyer, A. O., Slack, R. S., Skerjanc, I. S., Lach, B., Craig, J., Jardine, K., McBurney, M. W., Macaulay, R. J. B., Dimitroulakos, J., Becker, L. E., Yeger, H., Rhodes, C. Harker, Honsinger, Charles, Sorenson, George D., Goumnerova L. C., Segal R. A., Kwon Y. K., Stiles C. D., Pomeroy S. L., Guha, A., Lau, N., Pawson, A., Engel, Ute, Gutowski, Nick J., Bevan, Karen, Noble, Mark, Gladson, C. L., Pijuan, V., Olman, M. A., Gillespie, G. Y., Yacoub, I., Yamasaki, T., Enomoto, K., Moritake, K., Akiyama, Y., Kawahara, M., Maeno, T., Merzak, A., Parker, C., Koocheckpour, S., Sherbet, G. V., Pilkington, G. J., Martin, K., Akinwunmi, J., Rooprai, H. K., Kennedy, A., Linke, A., Ognjenovic, N., Fujiwara, T., Matsumoto, Y., Miyake, K., Shin, M., Nagao, S., Pulido-Cejudo, G., Jamison, K., Hugenholtz, H., Campione-Piccardo, J., Maidment, S. L., Lins, C., Takyia, C. M., Garcia-Abreu, J., Rodrigues, F. F., Duarte, F., Chagas, C., Chneiweiss, H., and Neto, V. Moura

Published
1995
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