bluuebunny/crossref_metadata_2025 huggingface dataset:
MetNet: A two-level approach to reconstructing and comparing metabolic networks
Authors: Cocco Nicoletta , Llabrés Mercè , Reyes-Prieto Mariana , Simeoni Marta
Published: February 2021

Metabolic pathway comparison and interaction between different species can detect important information for drug engineering and medical science. In the literature, proposals for reconstructing and comparing metabolic networks present two main problems: network reconstruction requires usually human intervention to integrate information from different sources and, in metabolic comparison, the size of the networks leads to a challenging computational problem. We propose to automatically reconstruct a metabolic network on the basis of KEGG database information. Our proposal relies on a two-level representation of the huge metabolic network: the first level is graph-based and depicts pathways as nodes and relations between pathways as edges; the second level represents each metabolic pathway in terms of its reactions content. The two-level representation complies with the KEGG database, which decomposes the metabolism of all the different organisms into “reference” pathways in a standardised way. On the basis of this two-level representation, we introduce some similarity measures for both levels. They allow for both a local comparison, pathway by pathway, and a global comparison of the entire metabolism. We developed a tool, MetNet, that implements the proposed methodology. MetNet makes it possible to automatically reconstruct the metabolic network of two organisms selected in KEGG and to compare their two networks both quantitatively and visually. We validate our methodology by presenting some experiments performed with MetNet.
Anti-epileptic drug topiramate upregulates TGFβ1 and SOX9 expression in primary embryonic palatal mesenchyme cells: Implications for teratogenicity
Authors: Rafi Syed K. , Goering Jeremy P. , Olm-Shipman Adam J. , Hipp Lauren A. , Ernst Nicholas J. , Wilson Nathan R. , Hall Everett G. , Gunewardena Sumedha , Saadi Irfan
Published: February 2021

Topiramate is an anti-epileptic drug that is commonly prescribed not just to prevent seizures but also migraine headaches, with over 8 million prescriptions dispensed annually. Topiramate use during pregnancy has been linked to significantly increased risk of babies born with orofacial clefts (OFCs). However, the exact molecular mechanism of topiramate teratogenicity is unknown. In this study, we first used an unbiased antibody array analysis to test the effect of topiramate on human embryonic palatal mesenchyme (HEPM) cells. This analysis identified 40 differentially expressed proteins, showing strong connectivity to known genes associated with orofacial clefts. However, among known OFC genes, only TGFβ1 was significantly upregulated in the antibody array analysis. Next, we validated that topiramate could increase expression of TGFβ1 and of downstream target phospho-SMAD2 in primary mouse embryonic palatal mesenchyme (MEPM) cells. Furthermore, we showed that topiramate treatment of primary MEPM cells increased expression of SOX9. SOX9 overexpression in chondrocytes is known to cause cleft palate in mouse. We propose that topiramate mediates upregulation of TGFβ1 signaling through activation of γ-aminobutyric acid (GABA) receptors in the palate. TGFβ1 and SOX9 play critical roles in orofacial morphogenesis, and their abnormal overexpression provides a plausible etiologic molecular mechanism for the teratogenic effects of topiramate.
Viral RNA-binding ability conferred by SUMOylation at PB1 K612 of influenza A virus is essential for viral pathogenesis and transmission
Authors: Li Junping , Liang Libin , Jiang Li , Wang Qian , Wen Xia , Zhao Yuhui , Cui Pengfei , Zhang Yaping , Wang Guangwen , Li Qibing , Deng Guohua , Shi Jianzhong , Tian Guobin , Zeng Xianying , Jiang Yongping , Liu Liling , Chen Hualan , Li Chengjun
Published: February 2021

Posttranslational modifications, such as SUMOylation, play specific roles in the life cycle of invading pathogens. However, the effect of SUMOylation on the adaptation, pathogenesis, and transmission of influenza A virus (IAV) remains largely unknown. Here, we found that a conserved lysine residue at position 612 (K612) of the polymerase basic protein 1 (PB1) of IAV is a bona fide SUMOylation site. SUMOylation of PB1 at K612 had no effect on the stability or cellular localization of PB1, but was critical for viral ribonucleoprotein (vRNP) complex activity and virus replication in vitro. When tested in vivo, we found that the virulence of SUMOylation-defective PB1/K612R mutant IAVs was highly attenuated in mice. Moreover, the airborne transmission of a 2009 pandemic H1N1 PB1/K612R mutant virus was impaired in ferrets, resulting in reversion to wild-type PB1 K612. Mechanistically, SUMOylation at K612 was essential for PB1 to act as the enzymatic core of the viral polymerase by preserving its ability to bind viral RNA. Our study reveals an essential role for PB1 K612 SUMOylation in the pathogenesis and transmission of IAVs, which can be targeted for the design of anti-influenza therapies.
Deaf disability and employment in Brasilia: professional opportunity in event market
Authors: Oliveira Elane Pereira da Silva , Lima Letícia Bianca Barros de Moraes
Published: February 2021

This research paper's main objective is to analyze the employability for people with deaf disability in Brasilia, as a professional opportunity in the event market. The research highlights the variety of jobs, which could be performed by people with deaf disability, considering the event type proposed. The specific objectives were bounded as follows: to conceptualize the events and characterize the market employability; to identify and to present the placements inside the events for deaf disability. In order to reach those objectives, qualitative research has been performed involving a group of seven people with deaf disability, with almost none experience on Event Management tasks and six event management producers in Brasilia. In order to achieve the proposed objectives of this research, questionnaires were applied with ten objective questions and a subjective one via email with the questionnaire in Word to the event producers, and questionnaires for the deaf were applied in Libras via video and also via google forms, containing sixteen objective questions, which were submitted to data and discourse analysis using the Iramuteq software. Thoroughly observing the answers from both groups, a large opportunity to increase the job market in the event management areas in Brasilia has been identified.
Tanulás és innováció – Elméleti dilemmák és gyakorlati nézőpontok (Learning and innovation – Theoretical dilemmas and practical point of views)
Authors: Hámori Balázs
Published: February 2021

A tanulmány egy nemrég lezárt TÁMOP-kutatás keretébe illeszkedik.1 A kutatás célja, hogy átfogó képet nyújtson az innovációról, tisztázza az innovációval kapcsolatos fogalmakat, bemutassa az innovációs trendeket és – egy empirikus felmérés nyomán – számot adjon arról, hogy ezek hogyan jelentkeznek Magyarország sajátos viszonyai között. Az innovációs fogalomkör megvilágításához hozzátartozik a tanulás és az innováció kapcsolatának tisztázása. Bár a témáról a menedzsment-szakirodalomban számtalan mű jelenik meg, a szerző saját diszciplináris elkötelezettségének megfelelően közgazdasági nézőpontból igyekszik megközelíteni a problémakört. Végül megkísérli Magyarországot elhelyezni a tanulás nemzetközi térképén. _______ This research aims to provide a comprehensive view on innovation, to clarify innovation concepts, to present innovation trends, and – based on an empirical survey – to give an account about how they appear specific conditions of Hungary. The refining of innovation category includes clarification of the relationship between learning and innovation. While many works have been published in this topic of management literature, the author in accordance his own disciplinary engagement tries to approach the problem area from economic point of view. Finally he attempts to place Hungary on the international map of learning.
A sikeres növekedés és innováció feltételei (The condition of successful growth and innovation)
Authors: Dobák Miklós , Hortoványi Lilla , Szabó Zsolt Roland
Published: February 2021

Kutatásukban a szerzők a sikeres innovációs-növekedési stratégiák beazonosítására törekedtek két dimenzió mentén: növekedési erőfeszítés és innovációs erőfeszítés. A sikert mint a radikális innováció piaci bevezetéseként definiálták. A szakirodalom áttekintése és kvalitatív kutatási eredményeink alapján azt találták, hogy a siker feltételei a következők: (1) „felkészültség”, azaz biztos szakmai tudás (know-what); a (2) „gyakorlás”, azaz a folyamatok tökéletes ismerete (know-how); a (3) „tehetséggondozás”, azaz a megfelelő kapcsolati tőke a hiányzó képességek, erőforrások és információk megszerzéséhez (know-who); és végül a (4) „tehetség”, azaz kreativitás, magas asszociációs készség, és innovatív ötletek. A vezető feladata annak felismerése, hogy mikor szükséges lassítania a szervezetre nehezedő növekedési nyomáson. A nyugalmi időszakban továbbra is fontos az innovációs képességek fejlesztése. Következetesen fel kell ismernie, hogy mikor lesz nagyobb a szétaprózott erőforrások és a megosztott figyelem költsége, mint a potenciális hozadéka. _______ In present research the successful innovation-growth strategies are identified along two dimensions: growth effort and innovation effort. The success is defined as the introduction to the market of a radical innovation. After reviewing the literature and conducting a qualitative research, authors found that the threshold condition of success are the followings: (1) “preparation”, that is expertise (know-what); (2) “practice”, that is deep understanding of processes (know-how); (3) “talent support”, that is access to missing resources; and finally (4) “talent”, that is creativity, innovative idea, and high association capability. This is the role of the manager to decide when the organizational growth should be slowed down. While the development of innovation capability is still important in times of slow growth periods, the manager must recognize that the cost of divided attention and fragmented resources is higher, than the potential return of the innovation.
Continuing Medical Education Questions: February 2021
Authors: Carpenter Steven L.
Published: February 2021

Article Title: The Role of Noninvasive Tests in Clinical Gastroenterology Practices to Identify Patients With Non-Alcoholic Steatohepatitis at High Risk for Adverse Outcomes: Expert Panel Recommendations
CARRY TRADE YATIRIM STRATEJİSİ VE TÜRKİYE’DE BELİRLEYİCİLERİ
Authors: BİNGÖL Nergis , PEHLİVAN Ceren , HAN Ayşegül
Published: February 2021

Gelişen finansal piyasalarda, getiri arayışı artan yatırımcılar faiz oranı farklılıklarından yararlanmak amacıyla carry trade işlemlerine yönelmişlerdir. Carry trade yatırımcıları faiz oranları düşük olan ülkelerden borçlanıp yüksek faizli ülkelerde yatırım yaparak arada oluşan faiz farklarından yararlanmaktadırlar. Bu çalışmada da Türkiye’de carry trade yatırımlarının belirleyicileri araştırılmıştır. Çalışmada carry trade işlem hacmini temsilen yurt dışı yerleşiklerin net DİBS stoku verileri ve hisse senedi stok verileri kullanılmıştır. İki ülke enflasyon farkı, faiz oranı farkı, döviz kurundaki dalgalanma, S&P 500, BİST 100 değişkenlerinin etkisi incelenmiştir. Bunun içinde 2005: 01- 2019: 03 dönemindeki aylık verilere Hatemi-J- Irandoust Saklı Eşbütünleşme Testi uygulanmıştır. Analiz sonuçlarına göre bağımlı değişken ve bağımsız değişkenlerin pozitif ve negatif şokları arasında uzun dönemli ilişkinin olduğu görülmektedir. Dolayısıyla carry trade ve bağımsız değişkenler arasında saklı eşbütünleşme ilişkisinin olduğunu söylemek mümkündür.
İSLAMİ ENDEKSLERDEKİ PİYASA ETKİNLİĞİNİN UZUN HAFIZA MODELLERİYLE TEST EDİLMESİ: BİST UYGULAMASI
Authors: ÖZDEMİR Arife , GÜLCAN Nazlıgül , BOYACIOĞLU Namıka
Published: February 2021

Etkin piyasa, fiyatların rassal yürüyüş özelliğinden dolayı geçmişteki fiyat değişimlerini dikkate alarak gelecekteki fiyatların tahmin edilemediği; böylece fiyatlarda uzun hafızanın olmadığı piyasadır. Bu çalışmada, portföy çeşitlendirmesi açısından öneme sahip olan İslami endekslerin piyasa etkinliği uzun hafıza modelleriyle test edilmeye çalışılmıştır. BİST’te yer alan Katılım-30, Katılım-50 ve Model Portföy Endeksleri’nin yayınlandığı tarihten itibaren 11.04.2019’a kadar olan günlük getiri verileri dikkate alınarak getiri ve volatilite serilerinde uzun hafıza etkisi ARFIMA-FIGARCH modeli kullanılarak araştırılmıştır. Çalışmanın sonucunda, endekslerin getiri serilerinde kısa hafıza özelliği, volatilite serilerinde uzun hafıza özelliği sergilediği bulgusuna ulaşılmıştır. Türkiye’de yer alan İslami endekslerin incelenen dönem itibariyle uzun hafıza özelliğine sahip olması, bu endekslerin zayıf formda etkin piyasa yapısından uzaklaştıklarını göstermektedir.
Mejora del protocolo de cribado de diabetes gestacional: estudio de validación diagnóstica
Authors: Calero Rojas Miguel , Jurado Roger Aurora , Gutiérrez Grúa Marta , de la Peña Carretero Lourdes , Romero Sotomayor Victoria , López Braos Javier , Izquierdo Carrasco Federico , Herrero Tabanera Luis , Moreno Aguilar Carmen
Published: February 2021

Objetivos

El objetivo de este trabajo es evaluar la validez diagnóstica de dos métodos de cribado de diabetes mellitus gestacional (DMG).

Métodos

Se realizó un estudio prospectivo de validación diagnóstica en 2007 embarazadas. Las participantes fueron asignadas al grupo de alto o bajo riesgo, dependiendo de los factores de riesgo que presentaran. Se realizó una prueba de HbA1c simultáneamente al protocolo estándar basado en el test de O’Sullivan (TOS). Posteriormente, se aplicó un algoritmo que combinaba los resultados de ambos biomarcadores.

Resultados

En el grupo de bajo riesgo, el TOS mostró un área bajo la curva mayor (AUC 0,953; IC95% 0,915–0,992) que la prueba de HbA1c (0,688; IC 95% 0,541–0,834). El mejor punto de corte del TOS, 153,5 mg/dL (8,52 mmol/L), mostró mayor validez diagnóstica que el de la HbA1c, 28 mmol/mol (4,75%) y que el algoritmo basado en ambas pruebas. En el grupo de alto riesgo, el TOS mostró mejor rendimiento diagnóstico que la HbA1c y el algoritmo. Los puntos de corte óptimos para el TOS fueron mayores que los recomendados en los protocolos actuales. Semana 13: TOS AUC 0,882 (IC 95% 0,843–0,921), HbA1c AUC 0,624 (IC 95% 0,562–0,686), punto de corte para el TOS 140,5 mg/dL (7,8 mmol/L), punto de corte para la HbA1c 33 mmol/mol (5,15%). Semana 24: TOS AUC 0,944 (IC 95% 0,925–0,962), HbA1c AUC 0,642 (IC 95% 0,575–0,709), punto de corte para el TOS, 145,5 mg/dL (8,08 mmol/L), punto de corte para la HbA1c 29 mmol/mol (4,85%).

Conclusiones

El método para el cribado de DMG basado en el test de O’Sullivan con valores límite superiores a los recomendados fue el que mostró mejor validez diagnóstica. Si se hubieran aplicado estos umbrales, se habría evitado la prueba de sobrecarga oral de glucosa con 100 g al 55,6% y al 13,7% de las gestantes de bajo y alto riesgo.
Requirements for 5G Integrated Data Transfer in German Prehospital Emergency Care
Authors: Gaebel Jan , Bockelmann Carsten , Dekorsy Armin , Wendlandt Robert , Musiol Torsten , Neumann Juliane , Neumuth Thomas , Rockstroh Max
Published: February 2021

Data from preclinical emergency care is often not available in an integrated, electronic way. Data flow between ambulances and trauma centers lacks a communication approach that allows for efficient aggregation, transmission and reuse. We present the results of the requirement analysis for 5G-supported emergency care scenarios. With the illustarted requirements and derived structural consequences, we conclude with a proposal that will allow us to provide mechanisms and technologies to enable integrated emergency communication for preclinical care using modern communication technologies.
Telemedical consultation for remote islands
Authors: Dölger Lukas , Wendlandt Robert , Gräsner Jan-Thorsten , Renzing Niels
Published: February 2021

The following work gives an overview of telemedical consultation in emergencies based on a research project. A telemedical centre located at a university hospital offers medical expertise for rural islands independent from place, time and urgency. Medical employees on the islands were relieved in matters of responsibilities and received medical support whenever it is necessary. Results from the projects mid-term evaluation compare the innovative concept with the conventional approach.
Requirement Analysis for an Aerial Relay in Emergency Response Missions
Authors: Gruner Jonas , Bloße Albrecht , Rockstroh Max , Neumuth Thomas , Rostalski Philipp
Published: February 2021

First aid of patients at the scene of an emergency requires an adequate flow of information. The publicly funded research project MOMENTUM aims at seamlessly connecting the point of care to the hospital. An unmanned aerial vehicle serving as a network relay may help in cases of limited or no mobile wireless connection, e.g. due to topographical circumstances. The aerial system may also provide situational awareness in cases of mass casualty incidents. For these two defined use-cases, safety and stability considerations are discussed, and required flight times and payloads are defined. The relay can be connected to the ground via a cable or wireless connection. It is concluded that the use-cases can be realized best when using a multicopter-either combined with a cable for independent flight times and reliable data communication or a wireless solution to mitigate the risk from the increased payload while limiting flight time. For the first option, the payload of the aircraft should be adjusted to ensure the power consumption in hover matches the power limitation of the cable.
Investigating the influence of dielectric pads in 7T magnetic resonance imaging – simulated and experimental assessment
Authors: Garcia Maíra M. , Chaim Khallil T. , Otaduy Maria C. G. , Rennings Andreas , Erni Daniel , Vatanchi Maryam , Zylka Waldemar
Published: February 2021

Dipole radiofrequency (RF) elements have been successfully used to compose multi-channel RF coils for ultrahigh fields (UHF) magnetic resonance imaging (MRI). As magnetic components of RF fields (B1) can be very inhomogeneous at UHF (B0≥7T), dielectric pads with high dielectric constants were proposed to improve the B1 efficiency and homogeneity [1]. Dielectric pads can be used as a passive B1 shimmimg technique thanks to inducing a strong secondary magnetic field in their vicinity. The use of such dielectric pads affect not only the B1 field but also the electric field. This in turn affects the specific absorption rate (SAR) and consequently the temperature distribution inside the patient’s body. To study these effects, a 29 cm-long transmission dipole RF coil element terminated by two meander was used for 7T MRI [2]. Using a cylindrical agarose-gel phantom, numerical and experimental results were analyzed with respect to homogeneity and amplitude of the magnetic and electric fields generated by the RF element in various configurations with and without dielectric pads. Calculated and measured B1 results were cross-checked and found to be in good agreement. When using dielectric pads B1 homogeneity and magnitude increase in regions where it was previously weak or insufficient. Calculations suggest that SAR distribution will change when using the pads.
Deep-learning based reconstruction of the stomach from monoscopic video data
Authors: Hackner Ralf , Raithel Martin , Lehmann Edgar , Wittenberg Thomas
Published: February 2021

For the gastroscopic examination of the stomach, the restricted field of view related to the „keyhole“-perspective of the endoscope is known to be a visual limitation. Thus, a panoramic extension can enlarge the field of vision, supports the endoscopist during the examination, and ensures that all of the inner stomach walls are visually inspected. To compute such a panorama of the stomach, knowledge about the geometry of the underlying structure is required. Structure from motion an approach to reconstruct the necessary information about the 3D-structure from monocular image sequences as provided by a gastroscope. We examine and evaluate an existing deep neuronal network for stereo reconstruction, in order to approximate the geometry of stomach parts from a set of consecutive acquired image pairs from gastroscopic videos.
Estimating regional pulmonary blood flow in EIT with regularized deconvolution with a Tikhonov regularization
Authors: Augustin Xenia , Kircher Michael , Dössel Olaf , Stender Birgit , Bluth Thomas , Gama de Abreu Marcelo
Published: February 2021

Electrical Impedance Tomography (EIT) is a clinically used tool for bed-side monitoring of ventilation. Previous work also showed a high potential for lung perfusion monitoring with indicator-enhanced EIT. However, many research questions have yet to be answered before it can be broadly applied in clinical everyday life. The goal of this work is to evaluate a new method to improve EIT perfusion measurements. Pulmonary hemodynamic transfer functions were estimated using regularized deconvolution with Tikhonov regularization to estimate spatial perfusion parameters. The final comparison between EIT images and PET scans showed a median correlation of 0.897 for the images which were reconstructed using the regularized deconvolution. In comparison the previously used maximum slope method led to a median correlation of 0.868.
Evaluation of the Impact of Static Interference on an Empirical Data Based Static Magnetic Localization Setup for Capsule Endoscopy
Authors: Zeising Samuel , Anzai Daisuke , Thalmayer Angelika , Fischer Georg , Kirchner Jens
Published: February 2021

In this paper, the impact of interference due to the geomagnetic field on a static magnetic localization setup for capsule endoscopy, which is suitable for a wearable application, was investigated. For this purpose, a study was carried out in which the average abdomen size of 15 subjects was evaluated. With the determined geometry values, a setup consisting of three elliptical sensor rings was modeled. Simulations were performed, where the magnetic flux density was evaluated at the sensors by using different-sized magnets. The measured values were compared with each other and the geomagnetic flux density. The results revealed that the measured values were for all evaluated magnet sizes of the order of the geomagnetic flux density, which is problematic since the calibration of sensors is no longer valid if the orientation of the wearable sensor array is changed. However, it is suggested that a differential measurement is suitable for the proposed system and could reduce static interference caused by the geomagnetic field.
Sensitivity analysis of FDA´s benchmark nozzle regarding in vitro imperfections - Do we need asymmetric CFD benchmarks?
Authors: Stiehm Michael , Brandt-Wunderlich Christoph , Siewert Stefan , Schmitz Klaus-Peter , Grabow Niels , Goubergrits Leonid , Kühne Titus , Poon Eric K. W. , Ooi Andrew , Barlis Peter
Published: February 2021

Modern technologies and methods such as computer simulation, so-called in silico methods, foster the development of medical devices. For accelerating the uptake of computer simulations and to increase credibility and reliability the U.S. Food and Drug Administration organized an inter-laboratory round robin study of a generic nozzle geometry. In preparation of own bench testing experiment using Particle Image Velocimetry, a custom made silicone nozzle was manufactured. By using in silico computational fluid dynamics method the influence of in vitro imperfections, such as inflow variations and geometrical deviations, on the flow field were evaluated. Based on literature the throat Reynolds number was varied Rethroat = 500 ± 50. It could be shown that the flow field errors resulted from variations of inlet conditions can be largely eliminated by normalizing if the Reynolds number is known. Furthermore, a symmetric imperfection of the silicone model within manufacturing tolerance does not affect the flow as much as an asymmetric failure such as an unintended curvature of the nozzle. In brief, we can conclude that geometrical imperfection of the reference experiment should be considered accordingly to in silico modelling. The question arises, if an asymmetric benchmark for biofluid analysis needs to be established. An eccentric nozzle benchmark could be a suitable case and will be further investigated.
Reduced order method for finite difference modeling of cardiac propagation
Authors: Khan Riasat , Shahebul Hasan Shahebul Hasan , Ng Kwong
Published: February 2021

Efficient numerical simulation of cardiac electrophysiology is crucial for studying the electrical properties of the heart tissue. The cardiac bidomain model is the most widely accepted representation of the electrical behaviour of the heart muscle. The bidomain model offers fast cardiac potential variation, which can lead to high computational cost due to the required large grid sizes and small time steps. In this paper, the complexity of the finite difference approximation of the bidomain equations is reduced with the model order reduction technique. Proper orthogonal decomposition, a projection-based algorithm, is used to efficiently approximate the original high fidelity cardiac bidomain model with a low-dimensional system of equations. The low-dimensional basis functions are computed first from the ‘snapshots,’ which contain the solutions of the full-order system for different temporal and spatial parameters. Galerkin projection of the original cardiac bidomain system onto the subspace of the reduced order basis functions reduces the size of the linear system. Numerical results confirm the efficiency of the proposed reduced order modeling technique, reducing the simulation time by a factor of 9.54, while maintaining an RMS error of 0.769 mV between the original full order solution and the reduced order POD solution.
Analysis and visualisation of tremor dynamics in deep brain stimulation patients
Authors: Bremm Rene Peter , Koch Klaus Peter , Krüger Rejko , Gonçalves Jorge , Hertel Frank
Published: February 2021

Deep brain stimulation (DBS) is an established therapy for movement disorders such as in Parkinson's disease (PD) and essential tremor (ET). Adjusting the stimulation parameters, however, is a labour-intensive process and often requires several patient visits. Physicians prefer objective tools to improve (or maintain) the performance in DBS. Wearable motion sensors (WMS) are able to detect some manifestations of pathological signs, such as tremor in PD. However, the interpretation of sensor data is often highly technical and methods to visualise tremor data of patients undergoing DBS in a clinical setting are lacking. This work aims to visualise the dynamics of tremor responses to DBS parameter changes with WMS while patients performing clinical hand movements. To this end, we attended DBS programming sessions of two patients with the aim to visualise certain aspects of the clinical examination. PD tremor and ET were effectively quantified by acceleration amplitude and frequency. Tremor dynamics were analysed and visualised based on setpoints, movement transitions and stability aspects. These methods have not yet been employed and examples demonstrate how tremor dynamics can be visualised with simple analysis techniques. We therefore provide a base for future research work on visualisation tools in order to assist clinicians who frequently encounter patients for DBS therapy. This could lead to benefits in terms of enhanced evaluation of treatment efficacy in the future.
Automatic Classification of the Movements of Directed and Undirected Subviral Particles
Authors: Kaak Michelle , Rausch Andreas , Schanze Thomas
Published: February 2021

The development of drugs against pathogens that cause hemorrhagic fever, such as Marburg and Ebola virus, requires researchers to gather much information about the virus. The accelerating of the research process is of great interest; therefore a new algorithm was developed to analyze intracellular processes. The algorithm will classify the motion characteristics of subviral particles in fluorescence microscopic image sequences of Ebola or Marburg virusinfected cells. The classification is based on the calculation of mean squared displacement. The results look promising to distinguish different particle tracks in active and passive transport. The paper ends with a discussion.
Protein Adsorption Hysteresis and Transient States of Fibrinogen and BMP-2 as Model Mechanisms for Proteome-Binding to Implants
Authors: Jennissen H. P , Dohle Daniel S. , Zmbrink Thomas , Meißner Michael
Published: February 2021

Protein adsorption studies returned to the focus of medical therapeutics, when it was found that up to 2500 non-plasma proteins adsorbed to hip implants during arthroplastic surgery, challenging peri-implant healing models. Questions have re-emerged as to the implications of uncontrolled protein unfolding after adsorption. In past studies on the cooperativity of protein binding we discovered protein adsorption hysteresis, a thermodynamically irreversible process. The present precursory study comprises real-time kinetic (TIRF-Rheometry) and equilibrium (125I-tracer ) studies on the hysteretic binding of fibrinogen and rhBMP-2 to titanium and glass surfaces via transient states. Thermodynamic constants (GOn), as well as kinetically derived (K'A ) and hysteresis derived (K'HA ) association constants in the range of 106 to 1012 M-1lead to a consistent picture.
Development of UV-Reactive Electrospinning Method Based on Poly(ethylene glycol) diacrylate Crosslinking
Authors: Huling Jennifer , Lyko Beate , Illner Sabine , Fiedler Nicklas , Grabow Niels , Teske Michael
Published: February 2021

Electrospinning is a popular method for creating nonwoven fiber materials for a wide variety of applications. In the field of biomaterials, electrospun materials are favoured because of a high surface-to-volume ratio which can be useful for drug loading and release, and because nanoscale fibers mimic native tissue structures, improving cell interactions. However limitations exist with regards to traditional solvent evaporation-based electrospinning techniques. A new area of research into reactive electrospinning is investigating methods of electrospinning that rely on in situ crosslinking rather than solvent evaporation to stabilize fibers. These techniques can potentially reduce the waste of excess solvents and make it easier to electrospin water soluble polymers. In this work, UV photocrosslinked PEGDA is evaluated as a material for reactive electrospinning. To facilitate the electrospinning process poly(ethylene glycol) diacrylate (PEGDA) is combined with polyvinyl alcohol (PVA). PEGDA/PVA solutions can be successfully electrospun under constant UV light exposure to initiate the crosslinking of the PEGDA. Reactive electrospun fibers appear more stable immediately after spinning and after washing with water, indicating successful photo crosslinking.
Comparison of Resistive and Optical Strain Measurement for Early Fracture Detection
Authors: Carabello Alina , Neupetsch Constanze , Werner Michael , Rotsch Christian , Drossel Welf-Guntram , Zajonz Dirk
Published: February 2021

To increase learning success in surgical training, physical simulators are supplemented by measurement technology to generate and record objective feedback and error detection. An opportunity to detect fractures following hip stem implantation early can be measurement of occurring strains on bone surface. These strains can be determined while using strain gauges, digital image correlation (DIC) or photoelasticity. In this research strain gauges and DIC were compared regarding their suitability as strain measurement tools for use in physical simulators. Therefore a testing method was described to replicate the implantation of a hip stem. Testing devices modelled on a realistic prosthesis were pressed into prepared porcine femora in a two-step procedure with a material testing machine. The local strains occurring on bone surface were determined using an optical measurement system for DIC and strain gauges. The initial fractures in the tested femora are located medial-anterior in most cases (73,6%). With increasing indentation depth of the test device, the strains on bone surface increase. Comparing the local strains determined by DIC and strain gauges consistencies in curves are noticeable. Maximal determined strains before fracturing amount to 0,69% with strain gauges and 0,75% with DIC. In the range of the fracture gap, strain gradients are determined by using DIC. However the detected surfaces are of low quality caused by gaps and motion artefacts. The results show strains on bone surfaces for early fracture detection are measurable with strain gauges and DIC. DIC is assessed as less suitable compared to strain gauges. Furthermore strain gauges have greater level of integration and economic efficiency, so they are preferred the use in surgical training simulators.
Dual-Lead 55 mm Impedance Pneumography
Authors: Klum Michael , Urban Mike , Pielmus Alexandru-Gabriel , Orglmeister Reinhold
Published: February 2021

In recent years, respiratory monitoring has gained attention due to the high prevalence and severe consequences of sleep apnea, post-anesthesia respiratory instability and respiratory diseases. Nevertheless, respiratory monitoring oftentimes relies on obtrusive masks and belts, which are unsuitable for wearable, long-term monitoring. Impedance pneumography (IP) is a bioimpedance method aiming to assess respiratory parameters unobtrusively. However, most IP configurations require far-spaced electrodes. Based on our recent work on wearable IP, we propose a dual-lead, wearable IP setup with 55 mm electrode spacing to estimate respiratory flow and rate (RR). Using our recently presented multimodal patch stethoscope as well as commercial systems, we conducted a study including 10 healthy subjects which were recorded in the supine, lateral and prone position. Using time-delay neural networks, we achieved RR estimation errors below 0.6 breaths per minute and flow correlations of 0.88 with relative errors of 25 % to a pneumotachometer reference. We conclude that dual-lead IP increases the performance of respiratory signal estimation compared to a single lead and recommend research in the area of subject position dependency and movement artefacts.
Novel flexible endoscope concept with swiveling camera tip
Authors: Boese Axel , Arens Christoph , Friebe Michael
Published: February 2021

Endoscopy is an important modality in medical imaging. Thin flexible endoscopes are for example used to examine the upper airways, for gastroscopy procedures or lung inspection. With standard flexible endoscopes one can change the direction of view by bending the tip with the disadvantage of large space required due to the bending radius. With first experiences of a concept of a moveable camera head on the tip of rigid endoscopes, we now propose a novel design employing a swiveling camera for flexible endoscopes. This concept is based on the use of a shape memory wire used to control the movement of the camera, a flexible plastic flap joint for tight rotation and flexible printed circuits for the electronic connection. The prototype was realized in a first low cost setup using a 5,5 mm HD chip on the tip camera with LED light. The motion and imaging performance of the prototype allowed swiveling of the camera on the endoscope tip from straight view to 100° side view. The space needed in fully rotation was limited to 9mm with an overall diameter of the endoscope in straight view of only 5,6mm, but could even be further reduced in a more professional setup. The image quality is good, but close-up views appear blurry due to the fixed focus point of the low-cost camera. The presented steering concept of the camera is promising, as it could potentially improve imaging of narrow cavities using flexible endoscopes. Especially for “in office” examinations this principle could add value to diagnosis and patient comfort.
Medical Device Regulation and current challenges for the implementation of new technologies
Authors: Kaule Sebastian , Bock Andrea , Dierke Ariane , Siewert Stefan , Schmitz Klaus-Peter , Stiehm Michael , Klar Ernst , Leuchter Matthias , Lenarz Thomas , Zygmunt Marek , Schmidt Wolfram , Grabow Niels
Published: February 2021

The European Parliament and the European Council on May 26, 2017 decided to introduce the new regulatory framework for medical devices. The transitional period of the so called Medical Device Regulation (EU 2017/745, MDR) should end on May 26, 2020. Currently the European Commission is working on a proposal to postpone the application for one year to relieve pressure from all stakeholders allowing them to fully focus on priorities related to the coronavirus crisis. From this date or most likely from May 26, 2021, manufacturers must present a CE-certificate according to the new MDR requirements not only for novel medical devices, but also for approved medical devices which are already on the market. The MDR will significantly complicate the process of bringing medical devices into market due to the increased requirements for the CE-certification process, particularly concerning increased documentation effort. This involves a risk for the translation of innovative products due to an overload of the overall system (manufacturers, Notified Bodies, experts) and might lead to shrinkage of the product range of existing products. Thankfully, adaption of transitional periods, special regulations, extensions of deadlines and most probably postponement of the MDR application date will ensure that there will be no gaps in medical supply that endanger patients. Establishing and keeping the relevant regulatory expertise up to date and devoting the necessary financial, time and human resources that is the biggest immediate challenge the medium-sized medical technology sector is facing in the near future. The current article, written about one month before the initially expected end of the first transition period on May 26, 2020, summarized the main aspects of the current state of MDR implementation with respect to regulatory novelties, the current legal basis in Germany, transition periods and changes in the requirements of CE-certification relevant technical documentation. Furthermore, challenges for existing and innovative medical devices were shortly discussed using a new stent based therapy of the proximal Fallopian tubal stenosis and transcatheter aortic valve implantation as two examples.
Introducing a Linear Gamma Variate Fit to Measure Pulmonary Perfusion with Electrical Impedance Tomography
Authors: Schuderer Felix , Kircher Michael , Dössel Olaf , Stender Birgit , Bluth Thomas , Gama de Abreu Marcelo
Published: February 2021

The indicator dilution method (IDM) is one approach to measure pulmonary perfusion using Electrical Impedance Tomography (EIT). To be able to calculate perfusion parameters and to increase robustnes, it is necessary to approximate and then to separate the components of the measured signals. The component referring to the passage of the injected bolus through the pixels can be modeled as a gamma variate function, its parameters are often determined using nonlinear optimization algorithms. In this paper, we introduce a linear approach that enables higher robustnes and faster computation, and compare the linear and nonlinear fitting approach on data of an animal study.
EEG-Based Classification of the Driver Alertness State
Authors: Golz Martin , Thomas Sebastian , Schenka Adolf
Published: February 2021

GMLVQ (Generalized Matrix Relevance Learning Vector Quantization) is a method of machine learning with an adaptive metric. While training, the prototype vectors as well as the weight matrix of the metric are adapted simultaneously. The method is presented in more detail and compared with other machine learning methods employing a fixed metric. It was investigated how accurately the methods can assign the 6-channel EEG of 25 young drivers, who drove overnight in the simulation lab, to the two classes of mild and severe drowsiness. Results of cross-validation show that GMLVQ is at 81.7 ± 1.3 % mean classification accuracy. It is not as accurate as support-vector machines (SVM) and gradient boosting machines (GBM) and cannot exploit the potential of learning adaptive metrics in the case of EEG data. However, information is provided on the relevance of each signal feature from the weighting matrix.
A Concept for Context Awareness in Smart Environments
Authors: Bauer Jochen , Hechtel Michael , Holzwarth Martin , Sessner Julian , Franke Jörg , Wittenberg Thomas , Waldhör Klemens , Schena Annamaria , Falanga Annarita , Ristok Bruno , Böhle Florian
Published: February 2021

All aspects of daily life increasingly include digitization. So-called „smart home“ technologies, as well as „wearables“, are gaining attention from more and more dwellers. Therefore, sensor-based, individualized, AI-based services for improved post-intervention monitoring and therapy accompaniment will become feasible and possible if these systems offer a related context-awareness. This paper provides an approach on how to sense and interpret specific contexts with the help of wearables, smartwatches, smart home sensors, and emotion detection software.
ForeSight - AI-based Smart Living Platform Approach
Authors: Bauer Jochen , Hechtel Michael , Konrad Christoph , Holzwarth Martin , Mayr Andreas , Schneider Sven , Franke Jörg , Hoffmann Hilko , Zinnikus Ingo , Feld Thomas , Runge Mathias , Hinz Oliver
Published: February 2021

In the upcoming years, the internet of things (IoT) will enrich daily life. The combination of artificial intelligence (AI) and highly interoperable systems will bring contextsensitive multi-domain services to reality. This paper describes a concept for an AI-based smart living platform with open- HAB, a smart home middleware, andWeb of Things (WoT) as key components of our approach. The platform concept considers different stakeholders, i.e. the housing industry, service providers, and tenants. These activities are part of the Fore- Sight project, an AI-driven, context-sensitive smart living platform.
Contactless Interactive Fall Detection and Sleep Quality Estimation for Supporting Elderly with Incipient Dementia
Authors: Siedel Roman , Scheck Tobias , Perez Grassi Ana C. , Seuffert Julian B. , Apitzsch André , Yu Jingrui , Nestler Norbert , Heinz Danny , Lehmann Lars , Goy Anne , Hirtz Gangolf
Published: February 2021

In recent years, the demographic change in conjunction with a lack of professional caregivers led to retirement homes reaching capacity. The Alzheimer Disease International stated that over 50 million people suffered from dementia in 2019 worldwide and twice the amount will presumably be effected in 2030. The field of Ambient Assisted Living (AAL) tackles this problem by facilitating technical system-aided everyday life. AUXILIA is such an AAL system and does not only support elderly people with dementia in an early phase, but also monitors their activities to provide behaviour analysis results for care attendants, relatives and physicians. Moreover, the system is capable of recognizing emergency situations like human falls. Furthermore, sleep quality estimation is employed to be able to draw conclusions about the current behaviour of an affected person. This article presents the current development state of AUXILIA.
Evaluation of semi-supervised learning using sparse labeling to segment cell nuclei
Authors: Bruch Roman , Rudolf Rüdiger , Mikut Ralf , Reischl Markus
Published: February 2021

The analysis of microscopic images from cell cultures plays an important role in the development of drugs. The segmentation of such images is a basic step to extract the viable information on which further evaluation steps are build. Classical image processing pipelines often fail under heterogeneous conditions. In the recent years deep neuronal networks gained attention due to their great potentials in image segmentation. One main pitfall of deep learning is often seen in the amount of labeled data required for training such models. Especially for 3D images the process to generate such data is tedious and time consuming and thus seen as a possible reason for the lack of establishment of deep learning models for 3D data. Efforts have been made to minimize the time needed to create labeled training data or to reduce the amount of labels needed for training. In this paper we present a new semisupervised training method for image segmentation of microscopic cell recordings based on an iterative approach utilizing unlabeled data during training. This method helps to further reduce the amount of labels required to effectively train deep learning models for image segmentation. By labeling less than one percent of the training data, a performance of 90% compared to a full annotation with 342 nuclei can be achieved.
Optimization of online particle counting with a 3D-printed bubble trap
Authors: Kurzhals Anja , Brandt-Wunderlich Christoph , Borowski Finja , Schmitz Klaus-Peter , Grabow Niels , Schmidt Wolfram , Gurung Jyoti
Published: February 2021

Particulate evaluation is needed for the approval of cardiovascular devices. Air bubbles lead to higher particle counts when light obscuration method (LOM) is used. The aim of the study was to test a custom made bubble trap that removes air bubbles (2 - 100 μm) from a flow circuit prior to online particle counting. Artificially generated air bubbles were counted with an online particle counter with and without the bubble trap. Air bubbles were reduced by about 71 % to 91 % by using the bubble trap.
Sulfated Hyaluronan coating of polyurethanebased implant materials
Authors: Kemkemer Ralf , Athanasopulu Kiriaki , Caltzidou Dimitra , Sekishita Asuka , Kutuzova Larysa , Lorenz Günter , Tanaka Masaru
Published: February 2021

Thermoplastic polycarbonate urethane elastomers (TPCU) are potential implant materials for treating degenerative joint diseases thanks to their adjustable rubberlike properties, their toughness, and their durability. We developed a water-containing high-molecular-weight sulfated hyaluronic acid-coating to improve the interaction of TPCU with the synovial fluid. It is suggested that trapped synovial fluid can act as a lubricant that reduces the friction forces and thus provides an enhanced abrasion resistance of TPCU implants. Aims of this work were (i) the development of a coating method for novel soft TPCU with high-molecular sulfated hyaluronic acid to increase the biocompatibility and (ii) the in vitro validation of the functionalized TPCUs in cell culture experiments.
Permeability and wettability of bioresorbable nanofiber nonwoven membranes
Authors: Großmann Swen , Oldenburg Jan , Ott Robert , Stiehm Michael , Schmitz Klaus-Peter , Siewert Stefan , Illner Sabine , Grabow Niels
Published: February 2021

Nanofiber nonwoven membranes produced by electrospinning provide the possibility to adjust mechanical material parameters as well as simultaneously the biologically relevant properties - a fundamental aspect in developing new implants and medical devices. Wettability and permeability are also of great importance, as they have a decisive influence on the release of drugs, cell attachment, degradability and finally the nutrient supply of the surrounding tissue. Within this work the wettability and permeability of several electrospun poly-L-lactide nonwovens, including different additives, were investigated and a correlation to membrane morphology was found. A potential modification of the permeability by the fluid viscosity was also investigated. The results form a fundamental building block in the development of permeable biodegradable implants and medical devices.