TY - JOUR A1 - Herkenhoff, Marcos Edgar A1 - Brödel, Oliver A1 - Dilarri, Guilherme A1 - Bajay, Miklos Maximiliano A1 - Frohme, Marcus A1 - Costamilan, Carlos André da Veiga Lima Rosa T1 - Characterization of Volatile Compounds in Amarillo, Ariana, Cascade, Centennial, and El Dorado Hops Using HS-SPME/GC-MS JF - Compounds N2 - Humulus lupulus L. (hops) is essential in brewing due to its contributions to bitterness, flavor, and aroma. This study compared the volatile profiles of five commercially important hop varieties—Amarillo, Ariana, Cascade, Centennial, and El Dorado—grown in their main regions of origin (United States for Amarillo, Cascade, and El Dorado; Germany for Ariana; and Brazil for Centennial). Headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME/GC-MS) enabled the identification of 312 volatile compounds, including monoterpenes (e.g., myrcene, linalool, geraniol), sesquiterpenes (e.g., humulene, caryophyllene), esters, alcohols, aldehydes, and ketones. Amarillo showed the highest myrcene content (22.61% of the total volatile area), while Centennial was distinguished by elevated γ-muurolene (20.59%), and El Dorado by the highest level of undecan-2-one (10.47%), highlighting marked varietal differences in key aroma-active constituents. Multivariate, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), clearly discriminated the five varieties: PC1 (41.04% of the variance) separated samples enriched in fruity/floral monoterpenes and esters from those dominated by woody/resinous sesquiterpenes, whereas PC2 (25.93% of the variance) reflected variation in medium-chain esters, ketones, and waxy compounds. These chemometric patterns demonstrate that both genetic background and growing region terroir strongly shape hop volatile composition and, consequently, aroma potential, providing brewers with objective criteria for selecting hop varieties to achieve specific sensory profiles in beer. KW - Humulus lupulus KW - PCA KW - PLS-DA KW - aroma profile KW - brewing science KW - gas chromatography-mass spectrometry KW - hops KW - terroir KW - volatile compounds Y1 - 2026 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-21029 SN - 2673-6918 VL - 6 IS - 1 PB - MDPI ER - TY - JOUR A1 - Khrutba, Viktoriia A1 - Nikitchenko, Yuliia A1 - Balykin, Ivan A1 - Nechyporenko, Alina A1 - Frohme, Marcus T1 - Academic & educational networking as a mechanism for the resilience of university cooperation in the digital era JF - European Journal of Interdisciplinary Issues N2 - The article investigates the evolution of digital educational networks as instruments of resilience and sustainability within German-Ukrainian higher education cooperation. Its primary objective is to analyze how academic networking contributes to maintaining educational continuity, fostering innovation, and strengthening institutional adaptability under crisis conditions. The study focuses on two representative initiatives, the Digital Teaching Network (DTN) and the Wildau-Kharkiv IT Bridge, which exemplify the transition from traditional digital platforms to interconnected network ecosystems. Methodologically, the research combines quantitative and qualitative approaches, including an online survey, focus group discussions, and content analysis of responses from 185 participants representing 21 universities in both countries. This mixed-method design enables a comprehensive understanding of the motivational, organizational, and social determinants of participation in educational networks. The analysis identifies four main categories of network actors, initiators, active collaborators, occasional participants, and observers, whose interaction defines the internal dynamics and resilience of such networks. The study’s findings demonstrate that networking serves as a key mechanism for sustaining academic interaction, enhancing educators’ digital competencies, and facilitating interdisciplinary collaboration. It further shows that niche educational networks, those focused on specific thematic or professional domains, play an increasingly important role in advancing specialized expertise and fostering trust-based partnerships beyond the lifespan of individual projects. The scientific novelty of the article lies in conceptualizing the shift from digital platforms as technical tools to educational networks as socio-institutional ecosystems. Practically, the results highlight the potential of network-based cooperation to support the sustainable development, modernization, and internationalization of Ukrainian higher education in the digital era. KW - digital competencies KW - digitalization of education KW - educational networks KW - international cooperation KW - networking KW - niche networks KW - university resilience Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-20957 UR - https://www.eujini.org.pl/index.php/journal/article/view/35 VL - 2 IS - 2 SP - 84 EP - 97 PB - East European Association of Scientists CY - Warszaw ER - TY - CHAP A1 - Hollmann, Susanne A1 - Regierer, Babette A1 - D'Elia, Domenica A1 - Frohme, Marcus A1 - Gruden, Kristina A1 - Pfeil, Juliane A1 - Baebler, Spela A1 - Sezerman, Ugur A1 - Evelo, Chris T. A1 - Erhart, Friederike A1 - Huppertz, Berthold A1 - Bongcam-Rudloff, Erik A1 - Trefois, Christophe A1 - Gruca, Aleksandra A1 - Duca, Deborah A1 - Colotti, Gianni A1 - Merino-Martinez, Roxana A1 - Ouzounis, Christos A1 - Hunewald, Oliver A1 - He, Feng A1 - Kremer, Andreas ED - Kalajdziski, Slobodan ED - Ackovska, Nevena T1 - Standardisation in life-science research - Making the case for harmonization to improve communication and sharing of data amongst researchers N2 - Modern, high-throughput methods for the analysis of genetic information, gene and metabolic products and their interactions offer new opportunities to gain comprehensive information on life processes. The data and knowledge generated open diverse application possibilities with enormous innovation potential. To unlock that potential skills in generating but also properly annotating the data for further data integration and analysis are needed. The data need to be made computer readable and interoperable to allow integration with existing knowledge leading to actionable biological insights. To achieve this, we need common standards and standard operating procedures as well as workflows that allow the combination of data across standards. Currently, there is a lack of experts who understand the principles and possess knowledge of the principles and relevant tools. This is a major barrier hindering the implementation of FAIR (findable, accessible, interoperable and reusable) data principles and the actual reusability of data. This is mainly due to insufficient and unequal education of the scientists and other stakeholders involved in producing and handling big data in life science that is inherently varied and complex in nature, and large in volume. Due to the interdisciplinary nature of life science research, education within this field faces numerous hurdles including institutional barriers, lack of local availability of all required expertise, as well as lack of appropriate teaching material and appropriate adaptation of curricula. KW - FAIR data KW - standardization KW - interoperability KW - standard operating procedures (SOPs) KW - quality management (QM) KW - quality control (QC) KW - education Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-20118 ER - TY - JOUR A1 - Li, Xiangkun A1 - Amirkhanyan, Zohrab A1 - Grebinyk, Anna A1 - Gross, Matthias A1 - Komar, Yuliia A1 - Riemer, Felix A1 - Asoyan, Aida A1 - Boonpornprasert, Prach A1 - Borchert, Paul A1 - Davtyan, Hakob A1 - Dmytriiev, Dmytro A1 - Frohme, Marcus A1 - Hoffmann, Andreas A1 - Krasilnikov, Mikhail A1 - Loisch, Gregor A1 - Lotfi, Zahra A1 - Müller, Frieder A1 - Schmitz, Michael A1 - Obier, Frank A1 - Oppelt, Anne A1 - Philipp, Sebastian A1 - Richard, Christopher A1 - Vashchenko, Grygorii A1 - Villani, Daniel A1 - Worm, Steven A1 - Stephan, Frank T1 - Demonstration of ultra-high dose rate electron irradiation at FLASHlab@PITZ JF - Physics in Medicine & Biology N2 - Objective. The photo injector test facility at DESY in Zeuthen (PITZ) is building up an R&D platform, known as FLASHlab@PITZ, for systematically studying the FLASH effect in cancer treatment with its high-brightness electron beams, which can provide a uniquely large dose parameter range for radiation experiments. In this paper, we demonstrate the capabilities by experiments with a reduced parameter range on a startup beamline and study the potential performance of the full beamline by simulations. Approach. To measure the dose, Gafchromic films are installed both in front of and after the samples; Monte Carlo simulations are conducted to predict the dose distribution during beam preparation and help understand the dose distribution inside the sample. Plasmid DNA is irradiated under various doses at conventional and ultra-high dose rate (UHDR) to study the DNA damage by radiations. Start-to-end simulations are performed to verify the performance of the full beamline. Main results. On the startup beamline, reproducible irradiation has been established with optimized electron beams and the delivered dose distributions have been measured with Gafchromic films and compared to FLUKA simulations. The functionality of this setup has been further demonstrated in biochemical experiments at conventional dose rate of 0.05 Gy s−1 and UHDR of several 105 Gy s−1 and a varying dose up to 60 Gy, with the UHDR experiments finished within a single RF pulse (less than 1 millisecond); the observed conformation yields of the irradiated plasmid DNA revealed its dose-dependent radiation damage. The upgrade to the full FLASHlab@PITZ beamline is justified by simulations with homogeneous radiation fields generated by both pencil beam scanning and scattering beams. Significance. With the demonstration of UHDR irradiation and the simulated performance of the new beamline, FLASHlab@PITZ will serve as a powerful platform for studying the FLASH effects in cancer treatment. KW - ultra-high dose rate KW - FLASH effect KW - electron beams KW - FLASHlab@PITZ Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-20092 VL - 70 IS - 5 PB - Institute of Physics Publishing (IOP) ER - TY - JOUR A1 - Narvekar, Prachiti A1 - Berriel Diaz, Mauricio A1 - Krones-Herzig, Anja A1 - Hardeland, Ulrike A1 - Strzoda, Daniela A1 - Stöhr, Sigrid A1 - Frohme, Marcus A1 - Herzig, Stephan T1 - Liver-specific loss of lipolysis-stimulated lipoprotein receptor triggers systemic hyperlipidemia in mice JF - Diabetes N2 - In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. In contrast, aberrantly high levels of triglycerides in the blood ("hypertriglyceridemia") represent a hallmark of the metabolic syndrome and type 2 diabetes. As hypertriglyceridemia has been identified as an important risk factor for cardiovascular complications, in this study we aimed to identify molecular mechanisms in aberrant triglyceride elevation under these conditions. To determine the importance of hepatic lipid handling for systemic dyslipidemia, we profiled the expression patterns of various hepatic lipid transporters and receptors under healthy and type 2 diabetic conditions. A differentially expressed lipoprotein receptor was functionally characterized by generating acute, liver-specific loss- and gain-of-function animal models. We show that the hepatic expression of lipid transporter lipolysis-stimulated lipoprotein receptor (LSR) is specifically impaired in mouse models of obesity and type 2 diabetes and can be restored by leptin replacement. Experimental imitation of this pathophysiological situation by liver-specific knockdown of LSR promotes hypertriglyceridemia and elevated apolipoprotein (Apo)B and E serum levels in lean wild-type and ApoE knockout mice. In contrast, genetic restoration of LSR expression in obese animals to wild-type levels improves serum triglyceride levels and serum profiles in these mice. The dysregulation of hepatic LSR under obese and diabetic conditions may provide a molecular rationale for systemic dyslipidemia in type 2 diabetes and the metabolic syndrome and represent a novel target for alternative treatment strategies in these patients. Y1 - 2009 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19954 VL - 58 IS - 5 SP - 1040 EP - 1049 PB - American Diabetes Association ER - TY - JOUR A1 - Reuner, Andy A1 - Hengherr, Steffen A1 - Mali, Brahim A1 - Förster, Frank A1 - Arndt, Detlev A1 - Reinhardt, Richard A1 - Dandekar, Thomas A1 - Frohme, Marcus A1 - Brümmer, Franz A1 - Schill, Ralph O. T1 - Stress response in tardigrades: differential gene expression of molecular chaperones JF - Cell Stress and Chaperones N2 - Semi-terrestrial tardigrades exhibit a remarkable tolerance to desiccation by entering a state called anhydrobiosis. In this state, they show a strong resistance against several kinds of physical extremes. Because of the probable importance of stress proteins during the phases of dehydration and rehydration, the relative abundance of transcripts coding for two α-crystallin heat-shock proteins (Mt-sHsp17.2 and Mt-sHsp19.5), as well for the heat-shock proteins Mt-sHsp10, Mt-Hsp60, Mt-Hsp70 and Mt-Hsp90, were analysed in active and anhydrobiotic tardigrades of the species Milnesium tardigradum. They were also analysed in the transitional stage (I) of dehydration, the transitional stage (II) of rehydration and in heat-shocked specimens. A variable pattern of expression was detected, with most candidates being downregulated. Gene transcripts of one Mt-hsp70 isoform in the transitional stage I and Mt-hsp90 in the anhydrobiotic stage were significantly upregulated. A high gene expression (778.6-fold) was found for the small α-crystallin heat-shock protein gene Mt-sHsp17.2 after heat shock. We discuss the limited role of the stress-gene expression in the transitional stages between the active and anhydrobiotic tardigrades and other mechanisms which allow tardigrades to survive desiccation. KW - alpha-crystallin protein KW - anhydrobiosis KW - cryptobiosis KW - heat-shock protein KW - tardigrada KW - Milnesium tardigradum Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19994 VL - 15 IS - 4 SP - 423 EP - 430 PB - Springer ER - TY - JOUR A1 - Przymus, Piotr A1 - Rykaczewski, Krzysztof A1 - Martín-Segura, Adrián A1 - Truu, Jaak A1 - De Santa Pau, Enrique Carrillo A1 - Kolev, Mikhail A1 - Naskinova, Irina A1 - Gruca, Aleksandra A1 - Sampri, Alexia A1 - Frohme, Marcus A1 - Nechyporenko, Alina T1 - Deep Learning in Microbiome Analysis: A Comprehensive Review of Neural Network Models JF - Frontiers in Microbiology N2 - Microbiome research, the study of microbial communities in diverse environments, has seen significant advances due to the integration of deep learning (DL) methods. These computational techniques have become essential for addressing the inherent complexity and high-dimensionality of microbiome data, which consist of different types of omics datasets. Deep learning algorithms have shown remarkable capabilities in pattern recognition, feature extraction, and predictive modeling, enabling researchers to uncover hidden relationships within microbial ecosystems. By automating the detection of functional genes, microbial interactions, and host-microbiome dynamics, DL methods offer unprecedented precision in understanding microbiome composition and its impact on health, disease, and the environment. However, despite their potential, deep learning approaches face significant challenges in microbiome research. Additionally, the biological variability in microbiome datasets requires tailored approaches to ensure robust and generalizable outcomes. As microbiome research continues to generate vast and complex datasets, addressing these challenges will be crucial for advancing microbiological insights and translating them into practical applications with DL. This review provides an overview of different deep learning models in microbiome research, discussing their strengths, practical uses, and implications for future studies. We examine how these models are being applied to solve key problems and highlight potential pathways to overcome current limitations, emphasizing the transformative impact DL could have on the field moving forward. KW - clasiffication KW - clustering KW - deep learning KW - natural language processing KW - microbiome Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19889 SN - 1664-302X VL - 15 PB - Frontiers ER - TY - CHAP A1 - Strelchuk, Yaroslav A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Gargin, Vitaliy A1 - Lupyr, Andrii A1 - Alekseeva, Victoriia ED - Shakhovska, Nataliya ED - Jiao, Jianbo ED - Izonin, Ivan ED - Chretien, Stephane T1 - Detection of stress using photoplethysmography T2 - Proceedings of the 7th International Conference on Informatics & Data-Driven Medicine (IDDM 2024) N2 - Stress is an important factor affecting human health, and its timely detection can significantly improve quality of life. This study addresses the current issue of identifying stress states using photoplethysmography signals obtained from the wearable Shimmer 3 sensor. The purpose of the study was to establish an effective approach for stress detection, specifically through the analysis of heart rate variability changes during different states: rest and stress. A distinctive feature of the research is the use of the air raid siren sound as a stress factor. The research methodology includes the collection and analysis of biosignals, allowing for the assessment of cardiovascular system functioning under the impact of stress factors. The results of the study demonstrated significant differences in heart rhythm indicators depending on the person's state, highlighting the potential of these metrics as a tool for health monitoring and stress detection. The paper proposes a new approach to using photoplethysmography for assessing stress responses, which may contribute to the development of personalized stress management methods. KW - air raid signal KW - cardiovascular system health KW - early stress detection KW - health monitoring KW - heart rate variability KW - personalized stress management KW - photoplethysmography KW - stress KW - wearable sensors Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19896 UR - https://ceur-ws.org/Vol-3892/short3.pdf VL - 3892 SP - 196 EP - 202 PB - RWTH Aachen ER - TY - JOUR A1 - Herkenhoff, Marcos Edgar A1 - Battistini, Carolina A1 - Praia, Ana Beatriz A1 - Rossini, Bruno Cesar A1 - dos Santos, Lucilene Delazari A1 - Brödel, Oliver A1 - Frohme, Marcus A1 - Saad, Susana Marta Isay T1 - The combination of omics strategies to evaluate starter and probiotic strains in the Catharina sour Brazilian-style beer JF - Food Research International N2 - Catharina sour, the first internationally recognized Brazilian beer, is characterized by fermentation with lactic acid bacteria (LAB), which may have probiotic potential, and the addition of fruit juice. This study aimed to evaluate the use of the starter Streptococcus thermophilus TH‐4 (TH‐4) and the probiotics Lacticaseibacillus paracasei F19 and 431, associated with Saccharomyces cerevisiae US-05, in the absence (control)/presence of passion fruit or peach juices. Evaluation proceeded during fermentation and storage by enumeration using pour-plate and qPCR; gene expressions of hop resistance; proteome by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS); and odor, flavor, and metabolome by Headspace Solid-Phase Microextraction (HS-SPME), coupled with the gas chromatography–mass spectrometry (GC–MS) analysis. We concluded that the strains studied are recommended for applications in sour beers, due to the presence of defense mechanisms like membrane adhesion and H+ pump. Furthermore, HS-SPME/GC-MS indicated that the strains may contribute to the beer flavor and odor. KW - craft beer KW - probiotic KW - qPCR KW - hop resistance genes KW - proteome KW - metabolome Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19858 VL - 167 PB - Elsevier ER - TY - JOUR A1 - Suzuki, Juliana Yumi A1 - Herkenhoff, Marcos Edgar A1 - Brödel, Oliver A1 - Cucick, Ana Clara Candelaria A1 - Frohme, Marcus A1 - Saad, Susana Marta Isay T1 - Exploring the potential of red pitaya pulp (Hylocererus sp.) as a plant-based matrix for probiotic delivery and effects on betacyanin content and flavoromics JF - Food Research International N2 - This study evaluated the potential of red pitaya pulp fermented with Lacticaseibacillus paracasei subsp. paracasei F-19 (F-19) as a base for probiotic products. Physicochemical parameters, sugar, betacyanin, and phenolic contents, and antioxidant activity were analyzed over 28 days at 4 °C and compared to a non-fermented pulp, and to a pulp fermented with Bifidobacterium animalis subsp. lactis BB-12 (BB-12). Volatile compounds were identified using HS-SPME/GC–MS. Probiotic viability during storage and survival through in vitro-simulated gastrointestinal tract (GIT) stress were assessed. Red pitaya pulp, rich in moisture (85.83 g/100 g), carbohydrates (11.65 g/100 g), and fibers (2.49 g/100 g), supported fermentation by both strains. F-19 and BB-12 lowered pH, with F-19 showing stronger acidification, and maintained high viability (8.85–8.90 log CFU/mL). Fermentation altered sugar profiles and produced unique volatile compounds, enhancing aroma and sensory attributes. F-19 generated 2-phenylethanol, a unique flavor compound, absent in BB-12. Phenolic content initially increased but antioxidant activity decreased during storage. Betacyanin remained stable for up to 14 days. Red pitaya improved F-19 viability through the simulated GIT, while BB-12 populations significantly decreased (p < 0.05). These results suggest red pitaya pulp is a promising plant-based matrix for F-19, offering protection during digestion and highlighting its potential as a functional food with enhanced bioactive compound bioavailability and sensory attributes. KW - Pitaya KW - probiotic KW - PMA-qPCR KW - betacyanin KW - prebiotic KW - metabolome Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19843 VL - 192 PB - Elsevier ER - TY - JOUR A1 - Herkenhoff, Marcos Edgar A1 - Brödel, Oliver A1 - Frohme, Marcus T1 - Aroma component analysis by HS-SPME/GC–MS to characterize Lager, Ale, and sour beer styles JF - Food Research International N2 - The world of beer is a rich tapestry woven with diverse styles, each with its unique character. Lager, known for its crispness, ferments at lower temperatures, while ale, at warmer ones, boasts a wide spectrum of aromas. Belgian beers dazzle with their complexity, from fruity Trappist ales to sour lambics. German wheat beers, like hefeweizens, charm with their effervescence and fruity undertones. India Pale Ales (IPAs) showcase a hoppy burst, while sour ales tantalize with their tanginess. Craftsmanship, history, and regional ingredients intertwine in this world of brewing, offering aficionados an array of delightful experiences. Research on craft beer aromas is limited, and molecular fingerprint could be crucial. To date, there have been no studies focused on characterizing compound profiles to differentiate beer styles. The Headspace Solid Phase Microextraction (HS-SPME) method provides a rapid and solvent-free approach to volatile compound. The present study aims to characterize the aroma profile of a wide range of beers by using HS-SPME/GC–MS technique combined with multivariate data processing. A total of 120 beer samples were collected and divided into five categories: Pilsen (n = 28); Lager (n = 23); Ale (n = 32); Sour (n = 24); and Belgian Ales (n = 13). Among the Pilsen beers, 18 unique compounds were found for beers with hop extract and hops, and 2 for beers with hop extract (Octyl acetate; and alpha-Terpineol). When comparing the remaining groups to each other, Belgian beers exhibited 5 unique compounds, and Lagers had one (nonanal). Sours and Ales did not have unique compounds but shared 2 distinct compounds with the Belgian group each. We concluded that Belgian beers are the most complex in terms of various aroma-related compounds, and that it is possible to distinguish beers that use pure hops from hop extract. KW - beer KW - sour beer KW - Belgian beer KW - Ale KW - Pilsen KW - Lager Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19830 VL - 194 PB - Elsevier ER - TY - JOUR A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Strelchuk, Yaroslav A1 - Omelchenko, Vladyslav A1 - Gargin, Vitaliy A1 - Ishchenko, Liudmyla A1 - Alekseeva, Victoriia T1 - Galvanic Skin Response and Photoplethysmography for Stress Recognition Using Machine Learning and Wearable Sensors JF - Applied Sciences N2 - This study investigates stress recognition using galvanic skin response (GSR) and photoplethysmography (PPG) data and machine learning, with a new focus on air raid sirens as a stressor. It bridges laboratory and real-world conditions and highlights the reliability of wearable sensors in dynamic, high-stress environments such as war and conflict zones. The study involves 37 participants (20 men, 17 women), aged 20–30, who had not previously heard an air raid siren. A 70 dB “S-40 electric siren” (400–450 Hz) was delivered via headphones. The protocol included a 5 min resting period, followed by 3 min “no-stress” phase, followed by 3 min “stress” phase, and finally a 3 min recovery phase. GSR and PPG signals were recorded using Shimmer 3 GSR+ sensors on the fingers and earlobes. A single session was conducted to avoid sensitization. The workflow includes signal preprocessing to remove artifacts, feature extraction, feature selection, and application of different machine learning models to classify the “stress “and “no-stress” states. As a result, the best classification performance was shown by the k-Nearest Neighbors model, achieving 0.833 accuracy. This was achieved by using a particular combination of heart rate variability (HRV) and GSR features, which can be considered as new indicators of siren-induced stress. KW - galvanic skin response KW - machine learning KW - photoplethysmography KW - stress Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19803 VL - 14 IS - 24 PB - MDPI ER - TY - JOUR A1 - Bilous, Nataliya A1 - Malko, Vladyslav A1 - Frohme, Marcus A1 - Nechyporenko, Alina T1 - Comparison of CNN-Based Architectures for Detection of Different Object Classes JF - AI N2 - (1) Background: Detecting people and technical objects in various situations, such as natural disasters and warfare, is critical to search and rescue operations and the safety of civilians. A fast and accurate detection of people and equipment can significantly increase the effectiveness of search and rescue missions and provide timely assistance to people. Computer vision and deep learning technologies play a key role in detecting the required objects due to their ability to analyze big volumes of visual data in real-time. (2) Methods: The performance of the neural networks such as You Only Look Once (YOLO) v4-v8, Faster R-CNN, Single Shot MultiBox Detector (SSD), and EfficientDet has been analyzed using COCO2017, SARD, SeaDronesSee, and VisDrone2019 datasets. The main metrics for comparison were mAP, Precision, Recall, F1-Score, and the ability of the neural network to work in real-time. (3) Results: The most important metrics for evaluating the efficiency and performance of models for a given task are accuracy (mAP), F1-Score, and processing speed (FPS). These metrics allow us to evaluate both the accuracy of object recognition and the ability to use the models in real-world environments where high processing speed is important. (4) Conclusion: Although different neural networks perform better on certain types of metrics, YOLO outperforms them on all metrics, showing the best results of mAP-0.88, F1-0.88, and FPS-48, so the focus was on these models. KW - EfficientDet KW - SSD KW - YOLO KW - deep learning KW - neural network KW - object detection Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19634 VL - 5 IS - 4 SP - 2300 EP - 2320 PB - MDPI ER - TY - CHAP A1 - Reshetnik, Viktor A1 - Muryzina, Irina A1 - Frohme, Marcus A1 - Alekseeva, Victoriia A1 - Dzyza, Alla A1 - Nechyporenko, Alina ED - Chumachenko, Dmytro ED - Golland, Polina ED - Yakovlev, Sergiy T1 - Uncertainty Estimation Method for Determining Bone Density in Patients with Infiltrating Intraductal Carcinoma Undergoing Anti-Cancer Therapy T2 - Proceedings of the 4th International Workshop of IT-professionals on Artificial Intelligence (ProfIT AI 2024) 2024, Cambridge, MA, USA, September 25-27, 2024 N2 - Identification of a bone density is crucial in all branches of medicine. Assessing bone density is a labor-intensive process. Bone density is quite unstable and depends on many factors, both physiological (aging, hormonal balance) and pathological (medication use, various underlying conditions). The aim of our study is to determine bone density in patients with malignant breast tumors undergoing anti-cancer therapy. Material and Methods. The study included 50 women aged 60-70 years who were diagnosed with infiltrating intraductal carcinoma. According to established protocols, MSCT is recommended for this category of women at intervals of once every six months. The first MSCT scan was performed immediately after the diagnosis was made, before the start of treatment, and the second scan was conducted six months later. Results. The maximum radiological density was 75.8954±37.9477 Hu in the group of women who had been receiving treatment for six months, compared to 93.9388±46.9694 Hu in the group of patients who did not take the drug. Meanwhile, the minimum density showed a slight increase from 29.7295±14.8647 Hu to 38.6919±19.3460 Hu, which can be attributed to the compensatory mechanisms of the body. Conclusions. In the course of this study, bone density in patients with infiltrating intraductal carcinoma undergoing anti-cancer therapy was determined using uncertainty estimation. It was found that after six months, the first to respond to changes in density was the maximum bone density. KW - infiltrarive intraductal adenocarcinoma KW - multislice computer tomography KW - radiological bone density Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19628 UR - https://ceur-ws.org/Vol-3777/short6.pdf IS - 3777 SP - 222 EP - 228 ER - TY - CHAP A1 - Nechyporenko, Alina A1 - Reshetnik, Viktor A1 - Frohme, Marcus A1 - Alekseeva, Victoriia A1 - Lupyr, Andrii A1 - Gargin, Vitaliy ED - Chumachenko, Dmytro ED - Golland, Polina ED - Yakovlev, Sergiy T1 - Evaluation of Bone Radiodensity in Smokers T2 - Proceedings of the 4th International Workshop of IT-professionals on Artificial Intelligence (ProfIT AI 2024) 2024, Cambridge, MA, USA, September 25-27, 2024 N2 - One of the most prevalent harmful habits that affect people daily is smoking. The aim of our study was to investigate changes in the bone density of the human paranasal sinuses under the influence of smoking using uncertainty calculation. Material and Methods. The study involved 150 male and female individuals aged 20-40 years, which helps to exclude other factors that could influence the reduction in bone radiodensity (e.g., menopause in women, age-related changes, etc.). The participants were divided into three groups based on the duration of their smoking habits. Results. Smoking has almost no effect on the maximum bone density. All groups show nearly identical values. In the first group, consisting of individuals who smoked for up to 5 years, the maximum density is 75.22 ± 37.61 Hu. In the second group, those who smoked for up to 10 years have a density of 84.22 ± 42.11 Hu, while in the third control group, the density is 74.29 ± 37.15 Hu. On the other hand, smoking has a greater impact on the minimum radiological bone density of the upper wall of the maxillary sinus. The lowest values are found in the group of individuals who smoked for 10 or more years, with a minimum density of 23.86 ± 11.93 Hu. For those who smoked for up to 5 years, the radiological bone density was 52.65 ± 26.32 Hu. In the control group, the density values were slightly higher than those of individuals who smoked for up to 5 years, with the highest values being 58.12 ± 29.06 Hu. Conclusion. The study investigated changes in the bone density of the human paranasal sinuses under the influence of smoking, utilizing uncertainty calculation. It was found that the most sensitive indicator to nicotine exposure is the minimum radiological density, which can significantly increase the risk of developing complications. Specifically, the lowest radiological density was observed in the group of individuals who smoked for 10 years or more, with a value of 23.86 ± 11.93 Hu. KW - bone radiodensity KW - computer tomography KW - paranasal sinus KW - uncertainty Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19616 UR - https://ceur-ws.org/Vol-3777/short8.pdf IS - 3777 SP - 238 EP - 244 ER - TY - JOUR A1 - Herkenhoff, Marcos Edgar A1 - Brödel, Oliver A1 - Frohme, Marcus T1 - Hops across Continents: Exploring How Terroir Transforms the Aromatic Profiles of Five Hop (Humulus lupulus) Varieties Grown in Their Countries of Origin and in Brazil JF - Plants N2 - Humulus lupulus, or hops, is a vital ingredient in brewing, contributing bitterness, flavor, and aroma. The female plants produce strobiles rich in essential oils and acids, along with bioactive compounds like polyphenols, humulene, and myrcene, which offer health benefits. This study examined the aromatic profiles of five hop varieties grown in Brazil versus their countries of origin. Fifty grams of pelletized hops from each strain were collected and analyzed using HS-SPME/GC-MS to identify volatile compounds, followed by statistical analysis with PLS-DA and ANOVA. The study identified 330 volatile compounds and found significant aromatic differences among hops from different regions. For instance, H. Mittelfrüher grown in Brazil has a fruity and herbaceous profile, while the German-grown variety is more herbal and spicy. Similar variations were noted in the Magnum, Nugget, Saaz, and Sorachi Ace varieties. The findings underscore the impact of terroir on hop aromatic profiles, with Brazilian-grown hops displaying distinct profiles compared to their counterparts from their countries of origin, including variations in aromatic notes and α-acid content. KW - HS-SPME/GC-MS KW - Humulus lupulus KW - aromatic profile KW - terroir impact KW - volatile compounds Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19470 VL - 13 IS - 19 ER - TY - JOUR A1 - Radivoievych, Aleksandar A1 - Schnepel, Sophia A1 - Prylutska, Svitlana A1 - Ritter, Uwe A1 - Zolk, Oliver A1 - Frohme, Marcus A1 - Grebinyk, Anna T1 - From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells JF - Cancers N2 - Recently, sonodynamic therapy (SDT) has emerged as a promising non-invasive approach for treating cancer by activating sensitizers with ultrasound (US). In this context, we investigated C60 fullerene (C60) as a nanocarrier for the promising drug Berberine (Ber)—both potential aromatic sonosensitizers. The preferential mitochondrial accumulation of C60 and the proapoptotic effects of Ber also make the C60-Berberine nanocomplex (C60-Ber) a good candidate for direct induction of the intrinsic apoptotic cell death under US action. The in vitro research on C60-Ber can provide insights into novel, non-invasive cancer treatments. These findings lead to the development of targeted therapies with reduced side effects, inspire interdisciplinary collaboration, and open new avenues for drug delivery and cancer therapy research. KW - berberine KW - C60 fullerene KW - apoptosis KW - sonodynamic therapy KW - ultrasound Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19438 VL - 16 IS - 18 ER - TY - CHAP A1 - Chumachenko, Dmytro A1 - Nechyporenko, Alina A1 - Frohme, Marcus ED - Shakhovska, Nataliya ED - Chrétien, Stéphane ED - Izonin, Ivan ED - Campos, Jaime T1 - Impact of Russian War on COVID-19 Dynamics in Germany: the Simulation Study by Statistical Machine Learning T2 - Proceedings of the 5th International Conference on Informatics & Data-Driven Medicine, Lyon, France, November 18 - 20, 2022 N2 - The new coronavirus COVID-19 has been spreading worldwide for almost three years. The global community has developed effective measures to contain and control the pandemic. However, new factors are emerging that are driving the dynamics of COVID-19. One of these factors was the escalation of Russia's war in Ukraine. This study aims to test the hypothesis of the influence of migration flows caused by the Russian war in Ukraine on the dynamics of the epidemic process in Germany. For this, a model of the COVID-19 epidemic process was built based on the polynomial regression method. The model's adequacy was tested 30 days before the start of the escalation of the Russian war in Ukraine. To assess the impact of the war on the dynamics of COVID-19, the model was used to calculate the forecast of cumulative new and fatal cases of COVID-19 in Germany in the first 30 days after the start of the escalation of the Russian war in Ukraine. Modeling showed that migration flows from Ukraine are not a critical factor in the growth of the dynamics of the incidence of COVID-19 in Germany, but they influenced the number of cases. The next stage of the study is the development of more complex models for a detailed analysis of population dynamics, identifying factors influencing the epidemic process in the context of the Russian war in Ukraine, and assessing their information content. KW - epidemic model KW - machine learning KW - polynomial regression KW - war KW - COVID-19 KW - infectious disease simulation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-19074 UR - https://ceur-ws.org/Vol-3302/short4.pdf VL - 3302 SP - 78 EP - 85 PB - RWTH Aachen ER - TY - JOUR A1 - Prylutska, Svitlana A1 - Grebinyk, Anna A1 - Ponomarenko, Stanislav A1 - Gövem, Defne A1 - Chumachenko, Vasyl A1 - Kutsevol, Nataliya A1 - Petrovsky, Mykola A1 - Ritter, Uwe A1 - Frohme, Marcus A1 - Piosik, Jacek A1 - Prylutskyy, Yuriy T1 - Toxicity of Water-Soluble D-g-PNIPAM Polymers in a Complex with Chemotherapy Drugs and Mechanism of Their Action In Vitro JF - International Journal of Molecular Sciences N2 - The application of a biocompatible polymer nanocarrier can provide target delivery to tumor tissues, improved pharmacokinetics, controlled drug release, etc. Therefore, the proposed strategy was to use the water-soluble star-like copolymers with a Dextran core and Poly(N-isopropylacrylamide) grafts (D-g-PNIPAM) for conjugation with the widely used chemotherapy drugs in oncology–Cisplatin (Cis-Pt) and Doxorubicin (Dox). The molecular characteristics of the copolymer were received using size-exclusion chromatography. The physicochemical characterization of the D-g-PNIPAM-Cis-Pt (or Dox) nanosystem was conducted using dynamic light scattering and FTIR spectroscopy. Using traditional biochemical methods, a comparative analysis of the enhancement of the cytotoxic effect of free Cis-Pt and Dox in combination with D-g-PNIPAM copolymers was performed in cancer cells of the Lewis lung carcinoma line, which are both sensitive and resistant to Dox; in addition, the mechanism of their action in vitro was evaluated. KW - star-like copolymer KW - drug KW - Lewis lung carcinoma KW - cytotoxicity Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18790 SN - 1422-0067 VL - 25 IS - 5 PB - MDPI ER - TY - CHAP A1 - Alekseeva, Victoriia A1 - Reshetnik, Viktor A1 - Frohme, Marcus A1 - Kachailo, Irina A1 - Murizyna, Irina A1 - Nechyporenko, Alina ED - Chumachenko, Dmytro ED - Kaur, Jasleen ED - Yakovlev, Sergiy ED - Morita, Plinio P. T1 - Investigation of the Impact of Insulin Resistance on the Bone Density of the Upper Wall of the Maxillary Sinus T2 - Proceedings of the 3rd International Workshop of IT-professionals on Artificial Intelligence, ProfIT AI 2023, Waterloo, Canada, November 20-22, 2023 N2 - The aim of our study was to investigate the impact of insulin resistance on the bone density of the upper wall of the maxillary sinus. Materials and Methods: The study included 100 female participants aged 18 to 44 years, divided into two groups. The first group consisted of individuals with insulin resistance, while the control group comprised individuals without signs of insulin resistance. In each group, we conducted an investigation of the radiological density of the upper wall of the maxillary sinus using uncertainty calculations. Results of the study suggest a potential influence of insulin resistance on the density of bone tissue around the nasal sinuses, specifically the upper wall of the maxillary sinus in our case. This parameter was found to be minimal in the group of individuals with insulin resistance. It is particularly noteworthy that both minimum and maximum bone density decreased in this group. Conclusions. The research focused on how insulin resistance affects the density of the upper wall of the maxillary sinus. By employing uncertainty calculations, the study revealed that insulin resistance is associated with a decrease in the minimum density of the upper wall of the maxillary sinus. This tendency may act as a catalyst for the emergence of significant inflammatory alterations in the nasal sinuses, serving as a foundation for the initiation of complications. KW - bone density KW - multispiral computer tomography KW - uncertainty KW - paranasal sinus KW - resistance to insulin Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0074-3641-3 UR - https://ceur-ws.org/Vol-3641/short1.pdf VL - 3641 SP - 216 EP - 223 PB - CEUR-WS.org ER - TY - CHAP A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Omelchenko, Vladyslav A1 - Alekseeva, Victoriia A1 - Lupyr, Andrii A1 - Gargin, Vitaliy ED - Shakhovska, Nataliya ED - Kovác, Michal ED - Izonin, Ivan ED - Chrétien, Stéphane T1 - Identification of Personality Based on the Sphenoid Sinus Structure Using Machine Learning T2 - Proceedings of the 6th International Conference on Informatics & Data-Driven Medicine, Bratislava, Slovakia, November 17-19, 2023 N2 - The aim of our study is to develop a new, simple, and effective method for identification of personality based on the characteristics of the sphenoid sinus structure, using machine learning for subsequent implementation into routine medical practice in Ukraine. The study involved 200 multislice computed tomography (MSCT) scans of individuals of various genders and ages. During the study, we obtained results with an accuracy exceeding 70%. KW - identification of personality KW - multislice computed tomography KW - deep learning Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0074-3609-1 UR - https://ceur-ws.org/Vol-3609/short2.pdf VL - 3609 SP - 167 EP - 173 PB - CEUR-WS.org ER - TY - CHAP A1 - Li, Xiangkun A1 - Amirkhanyan, Zohrab A1 - Aftab, Namra A1 - Boonpornprasert, Prach A1 - Dmytriiev, Dmytro A1 - Frohme, Marcus A1 - Georgiev, Georgi A1 - Grebinyk, Anna A1 - Gross, Matthias A1 - Hoffmann, Andreas A1 - Komar, Yuliia A1 - Krasilnikov, Mikhail A1 - Loisch, Gregor A1 - Oppelt, Anne A1 - Richard, Christopher A1 - Riemer, F. A1 - Philipp, Sebastian A1 - Schmitz, Michael A1 - Müller, Frieder A1 - Obier, Frank A1 - Vashchenko, Grygorii A1 - Worm, Steven A1 - Stephan, Frank T1 - Overview of FLASHlab@PITZ: the new R&D platform for FLASH radiation therapy and radiation biology T2 - Journal of Physics: Conference Series, Volume 2687, Applications of Accelerators, Technology Transfer and Industrial Relations and Outreach N2 - An R&D platform for electron FLASH radiation therapy and radiation biology is being prepared at the Photo Injector Test facility at DESY in Zeuthen (FLASHlab@PITZ). This platform is based on the unique beam parameters available at PITZ: ps scale electron bunches of up to 22 MeV with up to 5 nC bunch charge at MHz bunch repetition rate in bunch trains of up to 1 ms in length repeating at 1 to 10 Hz. It works together with the Technical University of Applied Sciences Wildau (TH Wildau) as partner in close vicinity for the biological resources. A startup beamline has been installed to allow dosimetry studies and irradiation experiments on chemical, biochemical and biological samples after a 60-degree dispersive arm. The measured dose and dose rates under different beam conditions and first experimental results will be reported in this paper. In addition, a dedicated beamline for FLASHlab@PITZhas been designed for better control of the high brightness electron beams. This includes a dogleg to translate the beam and a 2D kicker system to scan the tiny beam focused by quadrupoles across the samples within less than 1 ms. Simulation studies will be presented to demonstrate the extremely flexible dose parameters with various irradiation options for electron FLASH radiation therapy and radiation biology studies. Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18474 VL - 2687 PB - Institute of Physics Publishing (IOP) ER - TY - JOUR A1 - Marcos-Zambrano, Laura Judith A1 - López-Molina, Víctor Manuel A1 - Bakir-Gungor, Burcu A1 - Frohme, Marcus A1 - Karaduzovic-Hadziabdic, Kanita A1 - Klammsteiner, Thomas A1 - Ibrahimi, Eliana A1 - Lahti, Leo A1 - Loncar-Turukalo, Tatjana A1 - Dhamo, Xhilda A1 - Simeon, Andrea A1 - Nechyporenko, Alina A1 - Pio, Gianvito A1 - Przymus, Piotr A1 - Sampri, Alexia A1 - Trajkovik, Vladimir A1 - Lacruz-Pleguezuelos, Blanca A1 - Aasmets, Oliver A1 - Araujo, Ricardo A1 - Anagnostopoulos, Ioannis A1 - Aydemir, Önder A1 - Berland, Magali A1 - Calle, M. Luz A1 - Ceci, Michelangelo A1 - Duman, Hatice A1 - Gündoğdu, Aycan A1 - Havulinna, Aki S. A1 - Kaka Bra, Kardokh Hama Najib A1 - Kalluci, Eglantina A1 - Karav, Sercan A1 - Lode, Daniel A1 - Lopes, Marta B. A1 - May, Patrick A1 - Nap, Bram A1 - Nedyalkova, Miroslava A1 - Paciência, Inês A1 - Pasic, Lejla A1 - Pujolassos, Meritxell A1 - Shigdel, Rajesh A1 - Susín, Antonio A1 - Thiele, Ines A1 - Truică, Ciprian-Octavian A1 - Wilmes, Paul A1 - Yilmaz, Ercument A1 - Yousef, Malik A1 - Claesson, Marcus Joakim A1 - Truu, Jaak A1 - Carrillo de Santa Pau, Enrique T1 - A toolbox of machine learning software to support microbiome analysis JF - Frontiers in Microbiology N2 - The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis. KW - microbiome KW - machine learning KW - software KW - feature generation KW - feature analysis KW - data integration KW - microbial gene prediction KW - microbial metabolic modeling Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18271 UR - https://www.frontiersin.org/articles/10.3389/fmicb.2023.1250806/ SN - 1664-302X VL - 14 PB - Frontiers ER - TY - JOUR A1 - Shchotkina, Nataliia A1 - Palamarchuk, Y. A1 - Skorokhod, Iryna A1 - Dolinchuk, Liudmyla A1 - Sokol, Anatoliy A1 - Motronenko, Valentina A1 - Besarab, A. A1 - Gorchakova, N. A1 - Frohme, Marcus A1 - Herzog, Michael T1 - Features of technological regulation for cardiac bioimplants JF - Cell and Organ Transplantology N2 - Patients with congenital heart defects and cardiovascular diseases are required new approaches to surgical intervention. The use of biological cardiac implants, which are made from the extracellular matrix, is a promising trend in modern regenerative medicine. These bioimplants can completely replace defective tissue or organs, and when manufactured with strict protocols and quality control measures, can be safe and effective for therapeutic applications. The process of manufacturing bioimplants involves various risks that need to be assessed and mitigated with ongoing monitoring and evaluation necessary to ensure the highest standards of quality. Overall, this study was successfully evaluated the requirements for introducing a new medical device into practice and created a technical file that meets all necessary documentation for certification. KW - cardiac bioimplant KW - quality system KW - manufacturing risk management KW - technical regulation KW - medical device Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18248 SN - 2311-021X VL - 11 IS - 1 SP - 26 EP - 33 PB - Institute of Cell Therapy CY - Kiev ER - TY - JOUR A1 - Radivoievych, Aleksandar A1 - Prylutska, Svitlana A1 - Zolk, Oliver A1 - Ritter, Uwe A1 - Frohme, Marcus A1 - Grebinyk, Anna T1 - Comparison of Sonodynamic Treatment Set-Ups for Cancer Cells with Organic Sonosensitizers and Nanosonosensitizers JF - Pharmaceutics N2 - Cancer sonodynamic therapy (SDT) is the therapeutic strategy of a high-frequency ultrasound (US) combined with a special sonosensitizer that becomes cytotoxic upon US exposure. The growing number of newly discovered sonosensitizers and custom US in vitro treatment solutions push the SDT field into a need for systemic studies and reproducible in vitro experimental set-ups. In the current research, we aimed to compare two of the most used and suitable SDT in vitro set-ups—“sealed well” and “transducer in well”—in one systematic study. We assessed US pressure, intensity, and temperature distribution in wells under US irradiation. Treatment efficacy was evaluated for both set-ups towards cancer cell lines of different origins, treated with two promising sonosensitizer candidates—carbon nanoparticle C60 fullerene (C60) and herbal alkaloid berberine. C60 was found to exhibit higher sonotoxicity toward cancer cells than berberine. The higher efficacy of sonodynamic treatment with a “transducer in well” set-up than a “sealed well” set-up underlined its promising application for SDT in vitro studies. The “transducer in well” set-up is recommended for in vitro US treatment investigations based on its US-field homogeneity and pronounced cellular effects. Moreover, SDT with C60 and berberine could be exploited as a promising combinative approach for cancer treatment. KW - ultrasound KW - C60 fullerene KW - berberine KW - sonodynamic therapy KW - apoptosis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18223 SN - 1999-4923 VL - 15 IS - 11 PB - MDPI ER - TY - JOUR A1 - D'Elia, Domenica A1 - Truu, Jaak A1 - Lahti, Leo A1 - Berland, Magali A1 - Papoutsoglou, Georgios A1 - Ceci, Michelangelo A1 - Zomer, Aldert A1 - Lopes, Marta B. A1 - Ibrahimi, Eliana A1 - Gruca, Aleksandra A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Klammsteiner, Thomas A1 - Carrillo de Santa Pau, Enrique A1 - Marcos-Zambrano, Laura Judith A1 - Hron, Karel A1 - Pio, Gianvito A1 - Simeon, Andrea A1 - Suharoschi, Ramona A1 - Moreno-Indias, Isabel A1 - Temko, Andriy A1 - Nedyalkova, Miroslava A1 - Apostol, Elena-Simona A1 - Truică, Ciprian-Octavian A1 - Shigdel, Rajesh A1 - Telalović, Jasminka Hasić A1 - Bongcam-Rudloff, Erik A1 - Przymus, Piotr A1 - Jordamović, Naida Babić A1 - Falquet, Laurent A1 - Tarazona, Sonia A1 - Sampri, Alexia A1 - Isola, Gaetano A1 - Pérez-Serrano, David A1 - Trajkovik, Vladimir A1 - Klucar, Lubos A1 - Loncar-Turukalo, Tatjana A1 - Havulinna, Aki S. A1 - Jansen, Christian A1 - Bertelsen, Randi J. A1 - Claesson, Marcus Joakim T1 - Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action JF - Frontiers in Microbiology N2 - The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish “gold standard” protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory ‘omics’ features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices. KW - microbiome KW - machine learning KW - artificial intelligence KW - standard KW - best practice Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-18004 SN - 1664-302X VL - 14 PB - Frontiers ER - TY - JOUR A1 - Pfeil, Juliane A1 - Siptroth, Julienne A1 - Pospisil, Heike A1 - Frohme, Marcus A1 - Hufert, Frank T. A1 - Moskalenko, Olga A1 - Yateem, Murad A1 - Nechyporenko, Alina T1 - Classification of Microbiome Data from Type 2 Diabetes Mellitus Individuals with Deep Learning Image Recognition JF - Big Data and Cognitive Computing N2 - Microbiomic analysis of human gut samples is a beneficial tool to examine the general well-being and various health conditions. The balance of the intestinal flora is important to prevent chronic gut infections and adiposity, as well as pathological alterations connected to various diseases. The evaluation of microbiome data based on next-generation sequencing (NGS) is complex and their interpretation is often challenging and can be ambiguous. Therefore, we developed an innovative approach for the examination and classification of microbiomic data into healthy and diseased by visualizing the data as a radial heatmap in order to apply deep learning (DL) image classification. The differentiation between 674 healthy and 272 type 2 diabetes mellitus (T2D) samples was chosen as a proof of concept. The residual network with 50 layers (ResNet-50) image classification model was trained and optimized, providing discrimination with 96% accuracy. Samples from healthy persons were detected with a specificity of 97% and those from T2D individuals with a sensitivity of 92%. Image classification using DL of NGS microbiome data enables precise discrimination between healthy and diabetic individuals. In the future, this tool could enable classification of different diseases and imbalances of the gut microbiome and their causative genera. KW - human intestinal microbiome KW - next-generation sequencing KW - type 2 diabetes KW - deep learning KW - image classification Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-17184 SN - 2504-2289 VL - 7 IS - 1 PB - MDPI ER - TY - JOUR A1 - Alekseeva, Victoriia A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Gargin, Vitaliy A1 - Meniailov, Ievgen A1 - Chumachenko, Dmytro T1 - Intelligent Decision Support System for Differential Diagnosis of Chronic Odontogenic Rhinosinusitis Based on U-Net Segmentation JF - Electronics N2 - The share of chronic odontogenic rhinosinusitis is 40% among all chronic rhinosinusitis. Using automated information systems for differential diagnosis will improve the efficiency of decision-making by doctors in diagnosing chronic odontogenic rhinosinusitis. Therefore, this study aimed to develop an intelligent decision support system for the differential diagnosis of chronic odontogenic rhinosinusitis based on computer vision methods. A dataset was collected and processed, including 162 MSCT images. A deep learning model for image segmentation was developed. A 23 convolutional layer U-Net network architecture has been used for the segmentation of multi-spiral computed tomography (MSCT) data with odontogenic maxillary sinusitis. The proposed model is implemented in such a way that each pair of repeated 3 × 3 convolutions layers is followed by an Exponential Linear Unit instead of a Rectified Linear Unit as an activation function. The model showed an accuracy of 90.09%. To develop a decision support system, an intelligent chatbot allows the user to conduct an automated patient survey and collect patient examination data from several doctors of various profiles. The intelligent information system proposed in this study made it possible to combine an image processing model with a patient interview and examination data, improving physician decision-making efficiency in the differential diagnosis of Chronic Odontogenic Rhinosinusitis. The proposed solution is the first comprehensive solution in this area. KW - CT data KW - deep learning KW - image segmentation KW - U-Net KW - decision support system KW - chronic odontogenic rhinosinusitis KW - machine learning KW - artificial intelligence Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-17088 SN - 2079-9292 VL - 12 IS - 5 PB - MDPI ER - TY - JOUR A1 - Kober, Liane A1 - Schaefer, Paul A1 - Hollert, Henner A1 - Frohme, Marcus T1 - A novel strategy for high-throughput sample collection, analysis and visualization of explosives' concentrations for contaminated areas JF - International Journal of Environmental Science and Technology N2 - The use of explosives has led to a widespread distribution of 2,4,6-trinitrotoluene (TNT) and its by- and degradation products in the soil on former production and testing sites. The investigation of those large contaminated sites is so far based on a few selected soil samples, due to high costs of conventional HPLC and GC analysis, although huge differences in concentrations can already be found in small areas and different collection depths. We introduce a novel high-throughput screening system for those areas, which combines a smartphone-based collection of GPS data and soil characteristics with a fast MALDI-TOF MS quantification of explosives in soil sample extracts and finally a heatmap visualization of the explosives’ spread in soil and an analysis of correlation between concentrations and soil characteristics. The analysis of a 400 m2 area presented an extensive contamination with TNT and lower concentrations of the degradation and by-products aminodinitrotoluenes (ADNT) and dinitrotoluenes (DNT) next to a former production facility for TNT. The contamination decreased in deeper soil levels and depended on the soil type. Pure humus samples showed significantly lower contaminations compared to sand and humus/sand mixtures, which is likely to be caused by an increased binding potential of the humic material. No correlation was found between the vegetation and the concentration of explosives. Since the results were obtained and visualized within several hours, the MALDI-TOF MS based comprehensive screening and heatmap analysis might be valuable for a fast and high-throughput characterization of contaminated areas. KW - 2,4,6-trinitrotoluene KW - explosives KW - heatmap KW - MALDI-TOF MS KW - risk analysis KW - smartphone Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-15981 SN - 1735-2630 VL - 20 IS - 2 SP - 1399 EP - 1410 PB - Springer Nature ER - TY - JOUR A1 - Radivoievych, Aleksandar A1 - Kolp, Benjamin A1 - Grebinyk, Sergii A1 - Prylutska, Svitlana A1 - Ritter, Uwe A1 - Zolk, Oliver A1 - Glökler, Jörn A1 - Frohme, Marcus A1 - Grebinyk, Anna T1 - Silent Death by Sound: C60 Fullerene Sonodynamic Treatment of Cancer Cells JF - International Journal of Molecular Sciences N2 - The acoustic pressure waves of ultrasound (US) not only penetrate biological tissues deeper than light, but they also generate light emission, termed sonoluminescence. This promoted the idea of its use as an alternative energy source for photosensitizer excitation. Pristine C60 fullerene (C60), an excellent photosensitizer, was explored in the frame of cancer sonodynamic therapy (SDT). For that purpose, we analyzed C60 effects on human cervix carcinoma HeLa cells in combination with a low-intensity US treatment. The time-dependent accumulation of C60 in HeLa cells reached its maximum at 24 h (800 ± 66 ng/106 cells). Half of extranuclear C60 is localized within mitochondria. The efficiency of the C60 nanostructure’s sonoexcitation with 1 MHz US was tested with cell-based assays. A significant proapoptotic sonotoxic effect of C60 was found for HeLa cells. C60′s ability to induce apoptosis of carcinoma cells after sonoexcitation with US provides a promising novel approach for cancer treatment. KW - ultrasound KW - C60 fullerene KW - sonodynamic therapy KW - HeLa cells KW - apoptosis Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16877 SN - 1422-0067 VL - 24 IS - 2 PB - MDPI ER - TY - JOUR A1 - Praia, Ana Beatriz A1 - Herkenhoff, Marcos Edgar A1 - Brödel, Oliver A1 - Frohme, Marcus A1 - Saad, Susana Marta Isay T1 - Sour Beer with Lacticaseibacillus paracasei subsp. paracasei F19: Feasibility and Influence of Supplementation with Spondias mombin L. Juice and/or By-Product JF - Foods N2 - This study aimed to evaluate the probiotic strain Lacticaseibacillus (L.) paracasei subsp. paracasei F19 (F19) with the yeast Saccharomyces cerevisiae US-05 (US-05), using Spondias mombin L. (‘taperebá’ or ‘cajá’) juice and by-product, in four sour-type beer formulations: control, with bagasse, juice, and juice and bagasse. The viability of F19 was evaluated by pour-plating and PMA-qPCR. Fermentability, in addition to physicochemical and sensory parameters, and aroma and flavor, were evaluated during brewery by using Headspace Solid-Phase Microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry (GC–MS). F19 was successful in fermenting bagasse in a MRS medium (9.28 log CFU/mL in 24 h) but had a low viability in hopped wort, growing better in formulations without bagasse or juice. No difference between formulations was observed regarding sensory acceptability, and the HS-SPME/GC-MS revealed different flavors and aroma compounds. In conclusion, the production of a potential probiotic sour beer with F19 and US-05 is feasible regarding probiotic viability. However, S. mombin, as juice or bagasse, threatened probiotic survival. Different flavors and aroma compounds were detected, whereas no difference between formulations was found regarding sensory acceptability. The moderate alcohol content achieved is important for bacterial survival and for the development of a probiotic beer with health claims. KW - sour beer KW - probiotics KW - co-fermentation KW - fruit by-product Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16852 SN - 2304-8158 VL - 11 IS - 24 PB - MDPI ER - TY - JOUR A1 - Grebinyk, Anna A1 - Prylutska, Svitlana A1 - Grebinyk, Sergii A1 - Ponomarenko, Stanislav A1 - Virych, Pavlo A1 - Chumachenko, Vasyl A1 - Kutsevol, Nataliya A1 - Prylutskyy, Yuriy A1 - Ritter, Uwe A1 - Frohme, Marcus T1 - Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer JF - Nanoscale Advances N2 - The development of precision cancer medicine relies on novel formulation strategies for targeted drug delivery to increase the therapeutic outcome. Biocompatible polymer nanoparticles, namely dextran-graft-polyacrylamide (D-g-PAA) copolymers, represent one of the innovative non-invasive approaches for drug delivery applications in cancer therapy. In this study, the star-like D-g-PAA copolymer in anionic form (D-g-PAAan) was developed for pH-triggered targeted drug delivery of the common chemotherapeutic drugs – doxorubicin (Dox) and cisplatin (Cis). The initial D-g-PAA copolymer was synthesized by the radical graft polymerization method, and then alkaline-hydrolyzed to get this polymer in anionic form for further use for drug encapsulation. The acidification of the buffer promoted the release of loaded drugs. D-g-PAAan nanoparticles increased the toxic potential of the drugs against human and mouse lung carcinoma cells (A549 and LLC), but not against normal human lung cells (HEL299). The drug-loaded D-g-PAAan-nanoparticles promoted further oxidative stress and apoptosis induction in LLC cells. D-g-PAAan-nanoparticles improved Dox accumulation and drugs’ toxicity in a 3D LLC multi-cellular spheroid model. The data obtained indicate that the strategy of chemotherapeutic drug encapsulation within the branched D-g-PAAan nanoparticle allows not only to realize pH-triggered drug release but also to potentiate its cytotoxic, prooxidant and proapoptotic effects against lung carcinoma cells. Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16749 VL - 4 IS - 23 SP - 5077 EP - 5088 PB - Royal Society of Chemistry (RSC) ER - TY - JOUR A1 - Chumachenko, Dmytro A1 - Butkevych, Mykola A1 - Lode, Daniel A1 - Frohme, Marcus A1 - Schmailzl, Kurt J. G. A1 - Nechyporenko, Alina T1 - Machine Learning Methods in Predicting Patients with Suspected Myocardial Infarction Based on Short-Time HRV Data JF - Sensors N2 - Diagnosis of cardiovascular diseases is an urgent task because they are the main cause of death for 32% of the world’s population. Particularly relevant are automated diagnostics using machine learning methods in the digitalization of healthcare and introduction of personalized medicine in healthcare institutions, including at the individual level when designing smart houses. Therefore, this study aims to analyze short 10-s electrocardiogram measurements taken from 12 leads. In addition, the task is to classify patients with suspected myocardial infarction using machine learning methods. We have developed four models based on the k-nearest neighbor classifier, radial basis function, decision tree, and random forest to do this. An analysis of time parameters showed that the most significant parameters for diagnosing myocardial infraction are SDNN, BPM, and IBI. An experimental investigation was conducted on the data of the open PTB-XL dataset for patients with suspected myocardial infarction. The results showed that, according to the parameters of the short ECG, it is possible to classify patients with a suspected myocardial infraction as sick and healthy with high accuracy. The optimized Random Forest model showed the best performance with an accuracy of 99.63%, and a root mean absolute error is less than 0.004. The proposed novel approach can be used for patients who do not have other indicators of heart attacks. KW - myocardial infraction KW - heart rate variability KW - 10-second heart rate variability KW - diagnostics KW - machine learning KW - k-nearest neighbor classifier KW - radial basis function KW - decision tree KW - random forest Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16521 SN - 1424-8220 VL - 22 IS - 18 PB - MDPI ER - TY - JOUR A1 - Amro, Ahmad A1 - Moskalenko, Olga A1 - Hamarsheh, Omar A1 - Frohme, Marcus T1 - Spatiotemporal analysis of cutaneous leishmaniasis in Palestine and foresight study by projections modelling until 2060 based on climate change prediction JF - PLoS ONE N2 - Background Cutaneous leishmaniasis (CL) is a vector-borne parasitic diseases of public health importance that is prevalent in the West Bank but not in the Gaza Strip. The disease caused by parasitic protozoans from the genus Leishmania and it is transmitted by infected phlebotomine sand flies. The aim of our study is to investigate the eco-epidemiological parameters and spatiotemporal projections of CL in Palestine over a 30-years period from 1990 through 2020 and to explore future projections until 2060. Methodology/Principal findings This long-term descriptive epidemiological study includes investigation of demographic characteristics of reported patients by the Palestinian Ministry of Health (PMoH). Moreover, we explored spatiotemporal distribution of CL including future projection based on climate change scenarios. The number of CL patients reported during this period was 5855 cases, and the average annual incidence rate (AAIR) was 18.5 cases/105 population. The male to female ratio was 1.25:1. Patients-age ranged from 2 months to 89 years (mean = 22.5, std 18.67, and the median was 18 years). More than 65% of the cases came from three governates in the West Bank; Jenin 29% (1617 cases), Jericho 25% (1403), and Tubas 12% (658) with no cases reported in the Gaza Strip. Seasonal occurrence of CL starts to increase in December and peaked during March and April of the following year. Current distribution of CL indicate that Jericho, Tubas, Jenin and Nablus have the most suitable climatic settings for the sandfly vectors. Future projections until 2060 suggest an increasing incidence from northwest of Jenin down to the southwest of Ramallah, disappearance of the foci in Jericho and Tubas throughout the Jordan Vally, and possible emergence of new foci in Gaza Strip. Conclusions/Significance The future projection of CL in Palestine until 2060 show a tendency of increasing incidence in the north western parts of the West Bank, disappearance from Jericho and Tubas throughout the Jordan Vally, and emergence of new CL endemic foci in the Gaza Strip. These results should be considered to implement effective control and surveillance systems to counteract spatial expansion of CL vectors. Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16166 SN - 1932-6203 VL - 17 IS - 6 PB - Public Library of Science (PLoS) ER - TY - JOUR A1 - Kagel, Heike A1 - Frohme, Marcus A1 - Glökler, Jörn T1 - Photoacids in biochemical applications JF - Journal of Cellular Biotechnology N2 - BACKGROUND: After excitation with light photoacids can change the pH in a solution by release of a proton. They have been used mostly for excited state proton transfer studies. In this review the general functionality and mechanisms and the subdivision of photoacids is explained. STATE OF THE ART: Different uses of photoacids are described, covering a wide range of various biochemical topics, focusing on biochemical applications. Examples for the introduced subdivisions are covered. CONCLUSIONS AND OUTLOOK: The areas in which photoacids can be employed are diverse. Photoacids have a promising future in biotechnology and biochemistry and should be considered for upcoming applications, especially in non-invasive control of biochemical reactions. Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16123 SN - 2352-3697 VL - 4 IS - 1-2 SP - 23 EP - 30 PB - IOS Press ER - TY - JOUR A1 - Grebinyk, Anna A1 - Yashchuk, Valeriy A1 - Bashmakova, Nataliya A1 - Gryn, Dmytro A1 - Hagemann, Tobias A1 - Naumenko, Antonina A1 - Kutsevol, Nataliya A1 - Dandekar, Thomas A1 - Frohme, Marcus T1 - A new triple system DNA-Nanosilver-Berberine for cancer therapy JF - Applied Nanoscience N2 - The isoquinoline quaternary alkaloid Berberine possesses a variety of pharmacological properties that suggests its promising application for an anticancer delivery system design utilizing its ability to intercalate DNA. In the current work, we have investigated the effects of Berberine on the human T cell leukemia cell line in vitro. Fluorescent microscopy of leukemic cells revealed Berberine nuclear localization. The results showed that Berberine inhibited leukemic cell growth in a time- and dose-dependent manner, that was associated with reactive oxygen species production intensification and caspase 3/7 activity increase with followed apoptosis induction. Berberine was used as a toxic and phototoxic agent for triple system synthesis along with DNA as a carrier and nanosilver as a plasmonic accelerator of Berberine electronic transitions and high energy emission absorbent centers. The proposed method allows to obtain the complex of DNA with Berberine molecules and silver nanoparticles. The optical properties of free components as well as their various combinations, including the final triple system DNA-Nanosilver-Berberine, were investigated. Obtained results support the possibility to use the triple system DNA-Nanosilver-Berberine as an alternative therapeutic agent for cancer treatment. Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-16105 SN - 2190-5517 VL - 9 SP - 945 EP - 956 PB - Springer ER - TY - JOUR A1 - Pfeil, Juliane A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Hufert, Frank T. A1 - Schulze, Katja T1 - Examination of blood samples using deep learning and mobile microscopy JF - BMC Bioinformatics N2 - Microscopic examination of human blood samples is an excellent opportunity to assess general health status and diagnose diseases. Conventional blood tests are performed in medical laboratories by specialized professionals and are time and labor intensive. The development of a point-of-care system based on a mobile microscope and powerful algorithms would be beneficial for providing care directly at the patient's bedside. For this purpose human blood samples were visualized using a low-cost mobile microscope, an ocular camera and a smartphone. Training and optimisation of different deep learning methods for instance segmentation are used to detect and count the different blood cells. The accuracy of the results is assessed using quantitative and qualitative evaluation standards. Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-15802 SN - 1471-2105 VL - 23 PB - BioMed Central ER - TY - JOUR A1 - Herkenhoff, Marcos Edgar A1 - Bovolenta, Luiz A. A1 - Brödel, Oliver A1 - dos Santos, Lucilene Delazari A1 - de Oliveira, Arthur C. A1 - Chuffa, Luiz G.A. A1 - Ribeiro, Amanda O. A1 - Lupi, Luiz A. A1 - Dias, Marco A.D. A1 - Hilsdorf, Alexandre W.S. A1 - Frohme, Marcus A1 - Pinhal, Danillo T1 - Variant expression signatures of microRNAs and protein related to growth in a crossbreed between two strains of Nile tilapia (Oreochromis niloticus) JF - Genomics N2 - Nile tilapia (Oreochromis niloticus) is a species of worldwide importance for aquaculture. A crossbred lineage was developed through introgressive backcross breeding techniques and combines the high growth performance of the Chitralada (CHIT) lwith attractive reddish color of the Red Stirling (REDS) strains. Since the crossbreed has an unknown genetically improved background, the objective of this work was to characterize expression signatures that portray the advantageous phenotype of the crossbreeds. We characterized the microRNA transcriptome by high throughput sequencing (RNA-seq) and the proteome through mass spectrometry (ESI-Q-TOF-MS) and applied bioinformatics for the comparative analysis of such molecular data on the three strains. Crossbreed expressed a distinct set of miRNAs and proteins compared to the parents. They comprised several microRNAs regulate traits of economic interest. Proteomic profiles revealed differences between parental and crossbreed in expression of proteins associated with glycolisis. Distinctive miRNA and protein signatures contribute to the phenotype of crossbreed. KW - Nile tilapia KW - growth KW - RNA-seq KW - miRNA KW - ESI-Q-TOF KW - proteome Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-15571 SN - 0888-7543 VL - 113 IS - 6 SP - 4303 EP - 4312 PB - Elsevier ER - TY - CHAP A1 - Messaoudi, Hamza A1 - Das, Susanta Kumar A1 - Lange, Janine A1 - Heinrich, Friedhelm A1 - Schrader, Sigurd A1 - Frohme, Marcus A1 - Grunwald, Rüdiger T1 - Femtosecond laser induced nanostructuring for surface enhanced Raman spectroscopy N2 - The formation of periodical nanostructures with femtosecond laser pulses was used to create highly efficient substrates for surface-enhanced Raman spectroscopy (SERS). We report about the structuring of silver and copper substrates and their application to the SERS of DNA (herring sperm) and protein molecules (egg albumen). The maximum enhancement factors were found on Ag substrates processed with the second harmonic generation (SHG) of a 1-kHz Ti:sapphire laser and structure periods near the SHG wavelength. In the case of copper, however, the highest enhancement was obtained with long-period ripples induced with at fundamental wavelength. This is explained by an additional significant influence of nanoparticles on the surface. Nanostructured areas in the range of 1.25 mm2 were obtained in 10 s. The surfaces were characterized by scanning electron microscopy, Fast Fourier Transform and Raman spectroscopy. Moreover, the role of the chemical modification of the metal structures is addressed. Thin oxide layers resulting from working in atmosphere which improve the biocompatibility were indicated by vibration spectra. It is expected that the detailed study of the mechanisms of laser-induced nanostructure formation will stimulate further applications of functionalized surfaces like photocatalysis, selective chemistry and nano-biology. KW - laser-induced periodic surface structure KW - surface enhanced Raman spectroscopy KW - SERS KW - metal nanostructure KW - bio-molecule KW - DNA KW - femtosecond laser KW - ultrashort pulse Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-15252 SP - 61 EP - 68 PB - Society of Photo-Optical Instrumentation Engineers (SPIE) ER - TY - JOUR A1 - Glökler, Jörn A1 - Lim, Theam Soon A1 - Ida, Jeunice A1 - Frohme, Marcus T1 - Isothermal amplifications – a comprehensive review on current methods JF - Critical Reviews in Biochemistry and Molecular Biology N2 - AbstractThe introduction of nucleic acid amplification techniques has revolutionized the field of medical diagnostics in the last decade. The advent of PCR catalyzed the increasing application of DNA, not just for molecular cloning but also for molecular based diagnostics. Since the introduction of PCR, a deeper understanding of molecular mechanisms and enzymes involved in DNA/RNA replication has spurred the development of novel methods devoid of temperature cycling. Isothermal amplification methods have since been introduced utilizing different mechanisms, enzymes, and conditions. The ease with which isothermal amplification methods have allowed nucleic acid amplification to be carried out has had a profound impact on the way molecular diagnostics are being designed after the turn of the millennium. With all the advantages isothermal amplification brings, the issues or complications surrounding each method are heterogeneous making it difficult to identify the best approach for an end-user. This review pays special attention to the various isothermal amplification methods by classifying them based on the mechanistic characteristics which include reaction formats, amplification information, promoter, strand break, and refolding mechanisms. We would also compare the efficiencies and usefulness of each method while highlighting the potential applications and detection methods involved. This review will serve as an overall outlook on the journey and development of isothermal amplification methods as a whole. Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-15154 SP - 1 EP - 44 PB - Taylor & Francis ER - TY - CHAP A1 - Chepurna, Oksana A1 - Grebinyk, Anna A1 - Petrushko, Yulia A1 - Prylutska, Svitlana A1 - Grebinyk, Sergii A1 - Yashchuk, Valeriy A1 - Matyshevska, Olga A1 - Ritter, Uwe A1 - Dandekar, Thomas A1 - Frohme, Marcus A1 - Qu, Junle A1 - Ohulchanskyy, Tymish Y. T1 - LED-based portable light source for photodynamic therapy N2 - Photodynamic therapy (PDT) employs light activation of tissue-localized photosensitizer in an oxygen-dependent process which initiates oxidative stress, inflammation, and cell death. Laser systems, which are mostly used in PDT as light sources can be costly and oversized. light-emitting diodes (LEDs) equipment has a high potential to simplify technical part of phototriggered therapies and to reduce its costs. We develop the LED-based system that includes the control and irradiation units. The system provides the same power density at any irradiation point. Among the advantages of the device is a possibility to change the irradiation area and tune the irradiation dose. PDT experiments with cancer cells in vitro treated with two different photosensitizers demonstrated a possibility to use the developed LED-based system as a low-cost light source in PDT. KW - light source KW - high power single chip LED KW - photodynamic therapy Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-14778 ER - TY - JOUR A1 - Grebinyk, Anna A1 - Prylutska, Svitlana A1 - Grebinyk, Sergii A1 - Evstigneev, Maxim A1 - Krysiuk, Iryna A1 - Skaterna, Tetiana A1 - Horak, Iryna A1 - Sun, Yanfang A1 - Drobot, Liudmyla A1 - Matyshevska, Olga A1 - Prylutskyy, Yuriy A1 - Ritter, Uwe A1 - Frohme, Marcus T1 - Antitumor efficiency of the natural alkaloid berberine complexed with C60 fullerene in Lewis lung carcinoma in vitro and in vivo JF - Cancer Nanotechnology N2 - Background Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C60 fullerene (C60) at various molar ratios of the components, was explored against Lewis lung carcinoma (LLC). Methods C60–Ber noncovalent nanocomplexes were synthesized in 1:2, 1:1 and 2:1 molar ratios. Ber release from the nanocomplexes was studied after prolonged incubation at different pH with the liquid chromatography–mass spectrometry analysis of free Ber content. Biological effects of the free and C60-complaxated Ber were studied in vitro towards LLC cells with phase-contrast and fluorescence microscopy, flow cytometry, MTT reduction, caspase activity and wound closure assays. The treatment with C60–Ber nanocomplex was evaluated in vivo with the LLC-tumored C57Bl mice. The mice body weight, tumor size, tumor weight and tumor weight index were assessed for four groups, treated with saline, 15 mg C60/kg, 7.5 mg Ber/kg or 2:1 C60-Ber nanocomplex (15 mg C60/kg, 7.5 mg Ber/kg). Results Ber release from C60–Ber nanocomplexes was promoted with medium acidification. LLC cells treatment with C60–Ber nanocomplexes was followed by enhanced Ber intracellular uptake as compared to free Ber. The cytotoxicity of the studied agents followed the order: free Ber < 1:2 < 1:1 < 2:1 C60–Ber nanocomplex. The potency of cytotoxic effect of 2:1 C60–Ber nanocomplex was confirmed by 21.3-fold decrease of IC50 value (0.8 ± 0.3 µM) compared to IC50 for free Ber (17 ± 2 µM). C60–Ber nanocomplexes induced caspase 3/7 activation and suppressed the migration activity of LLC cells. The therapeutic potency of 2:1 C60–Ber nanocomplex was confirmed in a mouse model of LLC. The tumor growth in the group treated with 2:1 C60–Ber nanocomplex is suppressed by approximately 50% at the end of experiment, while in the tumor-bearing group treated with free Ber no therapeutic effect was detected. Conclusions This study indicates that complexation of natural alkaloid Ber with C60 may be a novel therapeutic strategy against lung carcinoma. Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-14749 SN - 1868-6966 VL - 12 SP - 24 PB - BioMed Central ER - TY - JOUR A1 - Kuhls, Katrin A1 - Moskalenko, Olga A1 - Sukiasyan, Anna A1 - Manukyan, Dezdemonia A1 - Melik-Andreasyan, Gayane A1 - Atshemyan, Liana A1 - Apresyan, Hripsime A1 - Strelkova, Margarita V. A1 - Jaeschke, Anja A1 - Wieland, Ralf A1 - Frohme, Marcus A1 - Cortes, Sofia A1 - Keshishyan, Ara T1 - Microsatellite based molecular epidemiology of Leishmania infantum from re-emerging foci of visceral leishmaniasis in Armenia and pilot risk assessment by ecological niche modeling JF - PLoS Neglected Tropical Diseases N2 - Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania. In Armenia visceral leishmaniasis (VL) is re-emerging since 1999 after a long break of 30 years, with 167 cases recorded until 2019. Molecular diagnosis of VL was implemented only in 2016, and the causative agent was identified as L. infantum. In the present study we expanded the investigation of the causative agent to a characterization at strain level and the identification of its phylogenetic position among the L. infantum genotypes circulating worldwide. This is the first study addressing genetic diversity and population structure of L. infantum in Armenia and in Transcaucasia. Armenia is an extremely interesting region due to its bio-geographic specificities e.g. the high number of different climates in this small mountainous country and the observed high diversity of sand fly species, part of which occurring in very high altitudes. Ecological niche modeling based on registered VL cases and sand fly vectors collected in active VL foci revealed that the risk of further spread of VL is very high due to climate change. Studies of this region should be expanded to enable targeted control measures. Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-14004 SN - 1935-2735 VL - 15 IS - 4 SP - e0009288 PB - Public Library of Science (PLoS) ER - TY - INPR A1 - Hollmann, Susanne A1 - Kremer, Andreas A1 - Baebler, Špela A1 - Trefois, Christophe A1 - Gruden, Kristina A1 - Rudnicki, Witold R. A1 - Tong, Weida A1 - Gruca, Aleksandra A1 - Bongcam-Rudloff, Erik A1 - Evelo, Chris T. A1 - Nechyporenko, Alina A1 - Frohme, Marcus A1 - Šafránek, David A1 - Regierer, Babette A1 - D'Elia, Domenica T1 - The need for standardisation in life science research - an approach to excellence and trust. [version 1; peer review: 3 approved] T2 - F1000Research N2 - Today, academic researchers benefit from the changes driven by digital technologies and the enormous growth of knowledge and data, on globalisation, enlargement of the scientific community, and the linkage between different scientific communities and the society. To fully benefit from this development, however, information needs to be shared openly and transparently. Digitalisation plays a major role here because it permeates all areas of business, science and society and is one of the key drivers for innovation and international cooperation. To address the resulting opportunities, the EU promotes the development and use of collaborative ways to produce and share knowledge and data as early as possible in the research process, but also to appropriately secure results with the European strategy for Open Science (OS). It is now widely recognised that making research results more accessible to all societal actors contributes to more effective and efficient science; it also serves as a boost for innovation in the public and private sectors. However for research data to be findable, accessible, interoperable and reusable the use of standards is essential. At the metadata level, considerable efforts in standardisation have already been made (e.g. Data Management Plan and FAIR Principle etc.), whereas in context with the raw data these fundamental efforts are still fragmented and in some cases completely missing. The CHARME consortium, funded by the European Cooperation in Science and Technology (COST) Agency, has identified needs and gaps in the field of standardisation in the life sciences and also discussed potential hurdles for implementation of standards in current practice. Here, the authors suggest four measures in response to current challenges to ensure a high quality of life science research data and their re-usability for research and innovation. KW - Open Data KW - Open Access KW - Open Science KW - FAIR Principles KW - standardisation KW - education KW - quality management Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-13891 SN - 2046-1402 VL - 9 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 - Pajčin, Ivana A1 - Vlajkov, Vanja A1 - Frohme, Marcus A1 - Grebinyk, Sergii A1 - Grahovac, Mila A1 - Mojićević, Marija A1 - Grahovac, Jovana T1 - Pepper Bacterial Spot Control by Bacillus velezensis: Bioprocess Solution JF - Microorganisms N2 - Pepper bacterial spot is one of the most severe plant diseases in terms of infection persistence and economic losses when it comes to fresh pepper fruits used in nutrition and industrial processing. In this study, Bacillus velezensis IP22 isolated from fresh cheese was used as a biocontrol agent of pepper bacterial spot, whose main causal agent is the cosmopolitan pathogen Xanthomonas euvesicatoria. After optimization of the cultivation medium composition aimed at maximizing of the antimicrobial activity against X. euvesicatoria and validation of the optimized medium at the scale of a laboratory bioreactor, in planta tests were performed. The results have showed significant suppression of bacterial spot symptoms in pepper plants by the produced biocontrol agent, as well as reduction of disease spreading on the healthy (uninoculated) pepper leaves. Furthermore, HPLC-MS (high pressure liquid chromatography–mass spectrometry) analysis was employed to examine antimicrobial metabolites produced by B. velezensis IP22, where lipopeptides were found with similar m/z values compared to lipopeptides from fengycin and locillomycin families. The bioprocess solution developed at the laboratory scale investigated in this study represents a promising strategy for production of pepper bacterial spot biocontrol agent based on B. velezensis IP22, a food isolate with a great perspective for application in plant protection. KW - Xanthomonas euvesicatoria KW - biological control KW - biocontrol agent KW - medium optimization KW - lipopeptide KW - fengycin KW - locillomycin KW - HPLC-MS KW - bioreactor KW - laboratory scale Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-13510 SN - 2076-2607 VL - 8 IS - 10 PB - MDPI ER - TY - JOUR A1 - Hollmann, Susanne A1 - Frohme, Marcus A1 - Endrullat, Christoph A1 - Kremer, Andreas A1 - D'Elia, Domenica A1 - Regierer, Babette A1 - Nechyporenko, Alina T1 - Ten simple rules on how to write a standard operating procedure JF - PLoS Computational Biology N2 - Research publications and data nowadays should be publicly available on the internet and, theoretically, usable for everyone to develop further research, products, or services. The long-term accessibility of research data is, therefore, fundamental in the economy of the research production process. However, the availability of data is not sufficient by itself, but also their quality must be verifiable. Measures to ensure reuse and reproducibility need to include the entire research life cycle, from the experimental design to the generation of data, quality control, statistical analysis, interpretation, and validation of the results. Hence, high-quality records, particularly for providing a string of documents for the verifiable origin of data, are essential elements that can act as a certificate for potential users (customers). These records also improve the traceability and transparency of data and processes, therefore, improving the reliability of results. Standards for data acquisition, analysis, and documentation have been fostered in the last decade driven by grassroot initiatives of researchers and organizations such as the Research Data Alliance (RDA). Nevertheless, what is still largely missing in the life science academic research are agreed procedures for complex routine research workflows. Here, well-crafted documentation like standard operating procedures (SOPs) offer clear direction and instructions specifically designed to avoid deviations as an absolute necessity for reproducibility. Therefore, this paper provides a standardized workflow that explains step by step how to write an SOP to be used as a starting point for appropriate research documentation. Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-13598 SN - 1553-7358 VL - 16 IS - 9 SP - e1008095 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 - Grebinyk, Anna A1 - Prylutska, Svitlana A1 - Chepurna, Oksana A1 - Grebinyk, Sergii A1 - Prylutskyy, Yuriy A1 - Ritter, Uwe A1 - Ohulchanskyy, Tymish Y. A1 - Matyshevska, Olga A1 - Dandekar, Thomas A1 - Frohme, Marcus T1 - Synergy of Chemo- and Photodynamic Therapies with C60 Fullerene-Doxorubicin Nanocomplex JF - Nanomaterials N2 - A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C60 fullerene (C60) were applied in 1:1 and 2:1 molar ratio, exploiting C60 both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox’s nuclear and C60’s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox’s antiproliferative activity and C60’s photoinduced pro-oxidant activity. When cells were treated with 2:1 C60-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C60-Dox enabled a nanomolar concentration of Dox and C60 to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC50 16, 9 and 7 × 103-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C60’s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C60-mediated Dox delivery and C60 photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C60-Dox nanoformulation provides a promising synergetic approach for cancer treatment. KW - photodynamic chemotherapy KW - synergistic effect KW - C60 fullerene KW - doxorubicin KW - nanocomplex KW - leukemic cell KW - apoptosis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-12940 SN - 2079-4991 VL - 9 IS - 11 PB - MDPI ER - TY - JOUR A1 - Grebinyk, Anna A1 - Prylutska, Svitlana A1 - Buchelnikov, Anatoliy A1 - Tverdokhleb, Nina A1 - Grebinyk, Sergii A1 - Evstigneev, Maxim A1 - Matyshevska, Olga A1 - Cherepanov, Vsevolod A1 - Prylutskyy, Yuriy A1 - Yashchuk, Valeriy A1 - Naumovets, Anton A1 - Ritter, Uwe A1 - Dandekar, Thomas A1 - Frohme, Marcus T1 - C60 Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells JF - Pharmaceutics N2 - A herbal alkaloid Berberine (Ber), used for centuries in Ayurvedic, Chinese, Middle-Eastern, and native American folk medicines, is nowadays proved to function as a safe anticancer agent. Yet, its poor water solubility, stability, and bioavailability hinder clinical application. In this study, we have explored a nanosized carbon nanoparticle—C60 fullerene (C60)—for optimized Ber delivery into leukemic cells. Water dispersions of noncovalent C60-Ber nanocomplexes in the 1:2, 1:1, and 2:1 molar ratios were prepared. UV–Vis spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM) evidenced a complexation of the Ber cation with the negatively charged C60 molecule. The computer simulation showed that π-stacking dominates in Ber and C60 binding in an aqueous solution. Complexation with C60 was found to promote Ber intracellular uptake. By increasing C60 concentration, the C60-Ber nanocomplexes exhibited higher antiproliferative potential towards CCRF-CEM cells, in accordance with the following order: free Ber < 1:2 < 1:1 < 2:1 (the most toxic). The activation of caspase 3/7 and accumulation in the sub-G1 phase of CCRF-CEM cells treated with C60-Ber nanocomplexes evidenced apoptosis induction. Thus, this study indicates that the fast and easy noncovalent complexation of alkaloid Ber with C60 improved its in vitro efficiency against cancer cells. KW - C60 fullerene KW - berberine KW - noncovalent nanocomplex KW - UV–Vis KW - DLS and AFM measurements KW - drug release KW - leukemic cell KW - uptake KW - cytotoxicity KW - apoptosis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-12932 SN - 1999-4923 VL - 11 IS - 11 PB - MDPI ER -