TY - JOUR A1 - Rothe, Felix A1 - Berger, Jörn A1 - Welker, Pia A1 - Fiebelkorn, Richard A1 - Kupper, Stefan A1 - Kiesel, Denise A1 - Gedat, Egbert A1 - Ohrndorf, Sarah T1 - Fluorescence optical imaging feature selection with machine learning for differential diagnosis of selected rheumatic diseases JF - Frontiers in Medicine N2 - Background and objective: Accurate and fast diagnosis of rheumatic diseases affecting the hands is essential for further treatment decisions. Fluorescence optical imaging (FOI) visualizes inflammation-induced impaired microcirculation by increasing signal intensity, resulting in different image features. This analysis aimed to find specific image features in FOI that might be important for accurately diagnosing different rheumatic diseases. Patients and methods: FOI images of the hands of patients with different types of rheumatic diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and connective tissue diseases (CTD), were assessed in a reading of 20 different image features in three phases of the contrast agent dynamics, yielding 60 different features for each patient. The readings were analyzed for mutual differential diagnosis of the three diseases (One-vs-One) and each disease in all data (One-vs-Rest). In the first step, statistical tools and machine-learning-based methods were applied to reveal the importance rankings of the features, that is, to find features that contribute most to the model-based classification. In the second step machine learning with a stepwise increasing number of features was applied, sequentially adding at each step the most crucial remaining feature to extract a minimized subset that yields the highest diagnostic accuracy. Results: In total, n = 605 FOI of both hands were analyzed (n = 235 with RA, n = 229 with OA, and n = 141 with CTD). All classification problems showed maximum accuracy with a reduced set of image features. For RA-vs.-OA, five features were needed for high accuracy. For RA-vs.-CTD ten, OA-vs.-CTD sixteen, RA-vs.-Rest five, OA-vs.-Rest eleven, and CTD-vs-Rest fifteen, features were needed, respectively. For all problems, the final importance ranking of the features with respect to the contrast agent dynamics was determined. Conclusions: With the presented investigations, the set of features in FOI examinations relevant to the differential diagnosis of the selected rheumatic diseases could be remarkably reduced, providing helpful information for the physician. KW - rheumatoid arthritis KW - osteoarthritis KW - connective tissue disease KW - gradient boosting machine KW - forward selection algorithm Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-17922 SN - 2296-858X VL - 10 PB - Frontiers ER - TY - JOUR A1 - Gossing, Wilhelm A1 - Frohme, Marcus A1 - Radke, Lars T1 - Biomarkers for Liquid Biopsies of Pituitary Neuroendocrine Tumors JF - Biomedicines N2 - Pituitary neuroendocrine tumors (PitNET) do not only belong to the most common intracranial neoplasms but seem to be generally more common than has been thought. Minimally invasive liquid biopsies have the potential to improve their early screening efficiency as well as monitor prognosis by facilitating the diagnostic procedures. This review aims to assess the potential of using liquid biopsies of different kinds of biomarker species that have only been obtained from solid pituitary tissues so far. Numerous molecules have been associated with the development of a PitNET, suggesting that it often develops from the cumulative effects of many smaller genetic or epigenetic changes. These minor changes eventually pile up to switch critical molecules into tumor-promoting states, which may be the key regulatory nodes representing the most potent marker substances for a diagnostic test. Drugs targeting these nodes may be superior for the therapeutic outcome and therefore the identification of such pituitary-specific cellular key nodes will help to accelerate their application in medicine. The ongoing genetic degeneration in pituitary adenomas suggests that repeated tumor profiling via liquid biopsies will be necessary for personalized and effective treatment solutions. KW - pituitary KW - biomarker KW - liquid biopsy KW - cfRNA KW - ctDNA KW - miRNA KW - epigenetics KW - lncRNA Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-13307 SN - 2227-9059 VL - 8 IS - 6 ER - TY - JOUR A1 - Gossing, Wilhelm A1 - Radke, Lars A1 - Biering, Henrik A1 - Diederich, Sven A1 - Mai, Knut A1 - Frohme, Marcus T1 - The ElonginB/C-Cullin5-SOCS-Box-Complex Is a Potential Biomarker for Growth Hormone Disorders JF - Biomedicines N2 - Insulin-like growth factor 1 (IGF-1) is the standard biochemical marker for the diagnosis and treatment control of acromegaly and growth hormone deficiency (GHD). However, its limitations necessitate the screening for new specific and sensitive biomarkers. The elonginB/C-cullin5-SOCS-box-complex (ECS-complex) (an intracellular five-protein complex) is stimulated by circulating growth hormone (GH) and regulates GH receptor levels through a negative feedback loop. It mediates the cells’ sensitivity for GH and therefore, represents a potent new biomarker for those diseases. In this study, individual ECS-complex proteins were measured in whole blood samples of patients with acromegaly (n = 32) or GHD (n = 12) via ELISA and compared to controls. Hierarchical clustering of the results revealed that by combining the three ECS-complex proteins suppressor of cytokine signaling 2 (SOCS2), cullin-5 and ring-box protein 2 (Rbx-2), 93% of patient samples could be separated from controls, despite many patients having a normal IGF-1 or not receiving medical treatment. SOCS2 showed the best individual diagnostic performance with an overall accuracy of 0.93, while the combination of the three proteins correctly identified all patients and controls. This resulted in perfect sensitivity and specificity for all patient groups, which demonstrates potential benefits of the ECS-complex proteins as clinical biomarkers for the diagnostics of GH-related diseases and substantiates their important role in GH metabolism. KW - acromegaly KW - growth hormone deficiency KW - biomarker KW - SOCS2 KW - liquid biopsy KW - pituitary Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-13802 SN - 2227-9059 VL - 9 IS - 2 PB - MDPI ER - TY - JOUR A1 - Marehn, David Thomas A1 - Wilhelm, Detlef A1 - Pospisil, Heike A1 - Pizzoferrato, Roberto T1 - Double entry method for the verification of data a chromatography data system receives JF - Journal of Sensors and Sensor Systems N2 - The importance of software validation increases since the need for high usability and suitability of software applications grows. In order to reduce costs and manage risk factors, more and more recommendations and rules have been established. In the field of pharmacy the vendors of so-called chromatography data systems (CDSs) had to implement the guidelines of the Code of Federal Regulations Title 21 (CFR 21) during the last few years in order to fulfill the increasing requirements. The CFR 21 part 11 deals with electronic records and signatures. This part is binding for each company in the regulated environment that wishes to create, edit and sign electronic information instead of printing them on paper. Subsection CFR 21 part 11.10(h) explains how to perform an input check for manual user entries as well as for data that will be collected from an external device. In this article we present an approach performing the double entry method on data provided by the hardware instrument in order to investigate possible influences on the raw data by the handling CDS. A software tool has been written which allows us to communicate with a high-performance liquid chromatography (HPLC) detector and acquire data from it. The communication is completely independent of a CDS which is started separately and connected to the same system. Using this configuration we made a parallel data acquisition of two instances at the same time possible. Two CDSs have been tested and for at least one of them it has been shown that a comparison of the acquired data can be done as with the double entry method for the data verification. For the second CDS we checked whether it would be applicable after a few modifications. The given approach could be either used for a live data verification of produced raw data or as a single test during a software operational qualification to verify the data acquisition functionality of the software. Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-12349 SN - 2194-878X VL - 8 SP - 207 EP - 214 ER - TY - JOUR A1 - Tannenberg, Robert A1 - Tscheuschner, Georg A1 - Raab, Christopher A1 - Flemig, Sabine A1 - Döring, Sarah A1 - Ponader, Marco A1 - Thurmann, Melinda A1 - Paul, Martin A1 - Weller, Michael G. T1 - Simplified Sample Preparation and Lateral Flow Immunoassay for the Detection of Plant Viruses JF - Biosensors N2 - Lateral flow immunoassays (LFAs) are widely used for on-site testing; however, their use for the rapid detection of plant viruses in the field is often limited by inconvenient sample preparation. Here, we present a new sampling method and a simplified dipstick LFA format for the detection and monitoring of cowpea chlorotic mottle virus (CCMV) as a model plant pathogen. The assay employs a monoclonal mouse antibody for capture and a poly-clonal rabbit antibody conjugated to 80 nm gold nanoparticles for detection. Conventional sample and conjugate pads are omitted, allowing the test strips to be dipped directly into wells containing plant extract and antibody–gold conjugate. No plastic casing was required, which could lead to a reduction in waste. It was shown that CCMV concentrations as low as 3.5 μg/L or 350 pg per sample could be reliably detected in 15 min. Specificity tests confirmed that other plant viruses, cowpea mosaic virus (CPMV) and tobacco mosaic virus (TMV), did not produce false-positive results. In addition, we describe a new method for on-site sampling using a manual punch and a syringe equipped with a frit. This step combines grinding the sample, extraction, filtration, and reconstitution and mixing of the antibody-gold conjugate, enabling the analysis of punched leaf disks without laboratory equipment. When applied to CCMV-infected cowpea plants, the assay revealed systemic infection before visual symptoms became apparent. This work demonstrates that simplified LFAs combined with innovative sampling techniques can provide sensitive, specific, and rapid diagnostics for crop monitoring and support early intervention strategies in agriculture. KW - LFA format KW - Vigna unguiculata KW - cowpea chlorotic mottle virus KW - crop monitoring KW - lateral flow immunoassay KW - plant virus KW - sample preparation KW - waste reduction Y1 - 2026 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-21294 VL - 16 IS - 2 PB - MDPI ER - TY - JOUR A1 - Zesch, Christoph A1 - Finkelstein, Daniel A1 - Regehly, Martin A1 - Reif, Jürgen A1 - Schrader, Sigurd T1 - Efficient nanosecond barium nitrate Raman laser for the visible spectral range JF - Optics Express N2 - We report on the design and performance of two solid-state Raman lasers, pumped by a frequency-doubled Nd:YAG laser at 532 nm (8 ns FWHM, 10 Hz, up to 10 mJ), that generate either the first or second Stokes radiation with wavelengths of 563 nm and 598 nm. Barium nitrate crystals with a 1 cm² face area and lengths of 3 cm and 5 cm were used as the Raman-active medium in stable semi-spherical resonators. The Raman lasers produced first Stokes and second Stokes pulses, achieving pulse energies up to 2.3 mJ and conversion efficiencies up to 35% (first Stokes, 5 cm crystal) and 21% (second Stokes, 5 cm crystal). The output beams exhibit nearly Gaussian profiles with beam quality factors of M² = 1.67 and M² = 1.83, respectively. The proposed design and characterization demonstrated a Raman laser with high efficiency and superior beam quality. After subsequent frequency doubling, the output appears well dedicated for future differential absorption LiDAR (DIAL) applications. KW - Gaussian beam KW - laser source KW - Nd:YAG laser KW - Raman laser KW - solid state laser KW - ultraviolet laser Y1 - 2026 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-21320 VL - 34 IS - 4 SP - 6355 EP - 6363 PB - Optica ER - TY - JOUR A1 - Steglich, Patrick A1 - Mai, Christian A1 - Villringer, Claus A1 - Dietzel, Birgit A1 - Bondarenko, Siegfried A1 - Ksianzou, Viachaslau A1 - Villasmunta, Francesco A1 - Zesch, Christoph A1 - Pulwer, Silvio A1 - Burger, Martin A1 - Bauer, Joachim A1 - Heinrich, Friedhelm A1 - Schrader, Sigurd A1 - Vitale, Francesco A1 - De Matteis, Fabio A1 - Prosposito, Paolo A1 - Casalboni, Mauro A1 - Mai, Andreas T1 - Silicon-organic hybrid photonics: an overview of recent advances, electro-optical effects and CMOS integration concepts JF - Journal of Physics: Photonics N2 - In recent decades, much research effort has been invested in the development of photonic integrated circuits, and silicon-on-insulator technology has been established as a reliable platform for highly scalable silicon-based electro-optical modulators. However, the performance of such devices is restricted by the inherent material properties of silicon. An approach to overcoming these deficiencies is to integrate organic materials with exceptionally high optical nonlinearities into a silicon-on-insulator photonic platform. Silicon–organic hybrid photonics has been shown to overcome the drawbacks of silicon-based modulators in terms of operating speed, bandwidth, and energy consumption. This work reviews recent advances in silicon–organic hybrid photonics and covers the latest improvements to single components and device concepts. Special emphasis is given to the in-device performance of novel electro-optical polymers and the use of different electro-optical effects, such as the linear and quadratic electro-optical effect, as well as the electric-field-induced linear electro-optical effect. Finally, the inherent challenges of implementing non-linear optical polymers on a silicon photonic platform are discussed and a perspective for future directions is given. Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-13882 SN - 2515-7647 VL - 3 IS - 2 ER - TY - JOUR A1 - Regehly, Martin A1 - Hecht, Stefan T1 - Split-Aperture Xolography – Linear Volumetric Photoactivation with Short Axial Dimension and Low out of Focus Excitation JF - Advanced Science N2 - Spatially confined photo-excitation with the lowest possible activation of the remaining volume is of central importance for high-resolution high-density optical data storage, fluorescence microscopy, 3D-lithography, and 3D-printing. Two-photon absorption (2PA) enables such applications yet leads to slow processing speed due to the underlying non-linear absorption process. Here, Split-Aperture Xolography (SAX), is introduced which uses stepwise excitation of dual-color responsive molecules to initiate a linear volumetric photo-reaction process that is up to several orders of magnitude more efficient than 2PA. The capabilities of SAX are investigated in a scenario study for focusing systems with high numerical aperture (NA) using a Python implementation of vectorial diffraction theory. The intersecting half-cones generated by the split illuminated entrance aperture of the objective reduce the axial focal spot size of the activation distribution by up to a factor of two compared to 2PA targeting the same electronic transition. A steep average decline of the activation probability with the fifth power away from focus is found for a wide range of directions. This is significantly better in comparison to 2PA and prevents that undesired out-of-focus excitation events sum-up with subsequent irradiations. This approach is expected to be advantageous for volumetric methods at the nanoscale. KW - photoswitch KW - split-aperture xolography KW - two-photon absorption KW - vectorial diffraction KW - volumetric 3D printing Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-20749 VL - 12 IS - 31 PB - Wiley ER - TY - JOUR A1 - Bauer, Joachim A1 - Heinrich, Friedhelm A1 - Villasmunta, Francesco A1 - Villringer, Claus A1 - Reck, Johanna A1 - Peters, Sven A1 - Treffer, Alexander A1 - Kuhnt, Christian A1 - Marschmeyer, Steffen A1 - Fursenko, Oksana A1 - Stolarek, David A1 - Mai, Andreas A1 - Regehly, Martin T1 - Reflectometric method for measuring residual oxides in through-silicon vias for 3D chip integration JF - Optics Express N2 - A significant aspect of fabricating 3D chip architectures is ensuring proper contact between the different layers of the chip, which often requires removing the underside of isolation layers before filling vias with conductive material. Currently, scanning electron microscopy is the established method for investigating such structures. In this paper, we propose a rapid, non-destructive optical analysis technique for the simultaneous measurement of through-silicon vias (TSV) depths, silicon wafer thickness, and residual oxide thickness. The proposed method utilizes Fourier peak shift analysis (FPSA) of reflectance measurements in the near-infrared (1200 nm—2200 nm) spectral regions. The application of FPSA to representative samples taken from a commercial TSV integration process for MEMS and CMOS fabrication demonstrated good agreement with reference scanning electron microscopy measurements, confirming the feasibility of the method for in-line and in-situ metrology. The results indicate that FPSA has great potential for real-time process monitoring and control during 3D chip manufacturing. KW - effective refractive index KW - Fourier transforms KW - near infrared KW - ray tracing KW - scanning electron microscopy KW - thin film Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-20633 VL - 33 IS - 15 SP - 32175 EP - 32189 PB - Optica ER - TY - JOUR A1 - Holland-Moritz, Ralph A1 - Vandenhouten, Ralf T1 - Detection of Movement Profiles in Facility Management Using Complex Event Processing JF - International Journal of Information Science N2 - This paper presents a solution for detecting movement and spreading profiles by analyzing sensor data in the facility management. First of all, a scenario is defined and described. On the basis of this scenario an approach is made using integration of events over time and location. For making the integration possible the required information, which the data objects have to provide, is identified. At the end a solution is presented using Complex Event Processing to implement the integration of events. KW - facility management KW - complex event processing KW - sensor KW - detector KW - movement profile KW - spatial dimension KW - integration KW - alarm reliability KW - event driven architecture KW - evaluation KW - security KW - intrusion KW - fire Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-9495 UR - http://article.sapub.org/10.5923.j.ijis.20130301.02.html SN - 2163-193X VL - 3 IS - 1 SP - 7 EP - 12 ER -