610 Medizin, Gesundheit
Refine
Document Type
- Journal article (82)
- Conference proceeding (82)
- Book chapter (8)
- Doctoral Thesis (2)
- Book (1)
- Patent / Standard / Guidelines (1)
- Report (1)
Is part of the Bibliography
- yes (177)
Institute
- Informatik (114)
- Life Sciences (47)
- Technik (8)
- ESB Business School (7)
Publisher
- Springer (40)
- Hochschule Reutlingen (17)
- Università Politecnica delle Marche (9)
- Elsevier (8)
- Deutsche Gesellschaft für Computer- und Roboterassistierte Chirurgie e.V. (7)
- MDPI (7)
- IEEE (6)
- IOP (6)
- SPIE (5)
- De Gruyter (4)
Radiofrequency ablation is an ablation technique to treat tumors with focused heat. Computer tomography, ultrasound and magnetic resonance imaging (MRI) are imaging modalities which can be used for image-guided procedures. MRI offers several advantages in comparison to the other imaging modalities, such as radiation-free fluoroscopic imaging, temperature mapping, a high-soft-tissue contrast and free selection of imaging planes. This work addresses the application of 3Dcontrollers for controlling interventional, fluoroscopic MR sequences at the scenario of MR guided radiofrequency ablation of hepatic malignancies. During this procedure, the interventionalist can monitor the targeting of the tumor with near-real time fluoroscopic sequences. In general, adjustments of the imaging planes are necessary during tumor targeting, which is performed by an assistant in the control room. Therefore, communication between the interventionalist in the scanner room and the assistant in the control room is essential. However, verbal communication is impaired due to the loud scanning noises. Alternatively, non-verbal communication between the two persons is possible, however limited to a few gestures and susceptible to misunderstandings. This work is analyzing different 3D-controllers to enable control of interventional MR sequences during MR-guided procedures directly by the interventionalist. Leap Motion, Wii Remote, SpaceNavigator, Phantom Omni and Foot Switch were selected. For that a simulation was built in C++ with VTK to feign the real scenario for test purposes. Previous results showed that Leap Motion is not suitable for the application while Wii Remote and Foot Switch are possible input devices. Final evaluation showed a generally time reduction with the use of 3D-controllers. Best results were reached with Wii Remote in 34 seconds. Handholding input devices like Wii Remote have further potential to integrate them in real environment to reduce intervention time.
Glioblastomas are the most aggressive fast-growing primary brain cancer which originate in the glial cells of the brain. Accurate identification of the malignant brain tumor and its sub-regions is still one of the most challenging problems in medical image segmentation. The Brain Tumor Segmentation Challenge (BraTS) has been a popular benchmark for automatic brain glioblastomas segmentation algorithms since its initiation. In this year, BraTS 2021 challenge provides the largest multi-parametric (mpMRI) dataset of 2,000 pre-operative patients. In this paper, we propose a new aggregation of two deep learning frameworksnamely, DeepSeg and nnU-Net for automatic glioblastoma recognition in pre-operative mpMRI. Our ensemble method obtains Dice similarity scores of 92.00, 87.33, and 84.10 and Hausdorff Distances of 3.81, 8.91, and 16.02 for the enhancing tumor, tumor core, and whole tumor regions, respectively, on the BraTS 2021 validation set, ranking us among the top ten teams. These experimental findings provide evidence that it can be readily applied clinically and thereby aiding in the brain cancer prognosis, therapy planning, and therapy response monitoring. A docker image for reproducing our segmentation results is available online at (https://hub.docker.com/r/razeineldin/deepseg21).
Intraoperative brain deformation, so called brain shift, affects the applicability of preoperative magnetic resonance imaging (MRI) data to assist the procedures of intraoperative ultrasound (iUS) guidance during neurosurgery. This paper proposes a deep learning-based approach for fast and accurate deformable registration of preoperative MRI to iUS images to correct brain shift. Based on the architecture of 3D convolutional neural networks, the proposed deep MRI-iUS registration method has been successfully tested and evaluated on the retrospective evaluation of cerebral tumors (RESECT) dataset. This study showed that our proposed method outperforms other registration methods in previous studies with an average mean squared error (MSE) of 85. Moreover, this method can register three 3D MRI-US pair in less than a second, improving the expected outcomes of brain surgery.
Purpose: Gliomas are the most common and aggressive type of brain tumors due to their infiltrative nature and rapid progression. The process of distinguishing tumor boundaries from healthy cells is still a challenging task in the clinical routine. Fluid attenuated inversion recovery (FLAIR) MRI modality can provide the physician with information about tumor infiltration. Therefore, this paper proposes a new generic deep learning architecture, namely DeepSeg, for fully automated detection and segmentation of the brain lesion using FLAIR MRI data.
Methods: The developed DeepSeg is a modular decoupling framework. It consists of two connected core parts based on an encoding and decoding relationship. The encoder part is a convolutional neural network (CNN) responsible for spatial information extraction. The resulting semantic map is inserted into the decoder part to get the full-resolution probability map. Based on modified U-Net architecture, different CNN models such as residual neural network (ResNet), dense convolutional network (DenseNet), and NASNet have been utilized in this study.
Results: The proposed deep learning architectures have been successfully tested and evaluated on-line based on MRI datasets of brain tumor segmentation (BraTS 2019) challenge, including s336 cases as training data and 125 cases for validation data. The dice and Hausdorff distance scores of obtained segmentation results are about 0.81 to 0.84 and 9.8 to 19.7 correspondingly.
Conclusion: This study showed successful feasibility and comparative performance of applying different deep learning models in a new DeepSeg framework for automated brain tumor segmentation in FLAIR MR images. The proposed DeepSeg is open source and freely available at https://github.com/razeineldin/DeepSeg/.
Purpose
Artificial intelligence (AI), in particular deep neural networks, has achieved remarkable results for medical image analysis in several applications. Yet the lack of explainability of deep neural models is considered the principal restriction before applying these methods in clinical practice.
Methods
In this study, we propose a NeuroXAI framework for explainable AI of deep learning networks to increase the trust of medical experts. NeuroXAI implements seven state-of-the-art explanation methods providing visualization maps to help make deep learning models transparent.
Results
NeuroXAI has been applied to two applications of the most widely investigated problems in brain imaging analysis, i.e., image classification and segmentation using magnetic resonance (MR) modality. Visual attention maps of multiple XAI methods have been generated and compared for both applications. Another experiment demonstrated that NeuroXAI can provide information flow visualization on internal layers of a segmentation CNN.
Conclusion
Due to its open architecture, ease of implementation, and scalability to new XAI methods, NeuroXAI could be utilized to assist radiologists and medical professionals in the detection and diagnosis of brain tumors in the clinical routine of cancer patients. The code of NeuroXAI is publicly accessible at https://github.com/razeineldin/NeuroXAI.
Automatic segmentation is essential for the brain tumor diagnosis, disease prognosis, and follow-up therapy of patients with gliomas. Still, accurate detection of gliomas and their sub-regions in multimodal MRI is very challenging due to the variety of scanners and imaging protocols. Over the last years, the BraTS Challenge has provided a large number of multi-institutional MRI scans as a benchmark for glioma segmentation algorithms. This paper describes our contribution to the BraTS 2022 Continuous Evaluation challenge. We propose a new ensemble of multiple deep learning frameworks namely, DeepSeg, nnU-Net, and DeepSCAN for automatic glioma boundaries detection in pre-operative MRI. It is worth noting that our ensemble models took first place in the final evaluation on the BraTS testing dataset with Dice scores of 0.9294, 0.8788, and 0.8803, and Hausdorf distance of 5.23, 13.54, and 12.05, for the whole tumor, tumor core, and enhancing tumor, respectively. Furthermore, the proposed ensemble method ranked first in the final ranking on another unseen test dataset, namely Sub-Saharan Africa dataset, achieving mean Dice scores of 0.9737, 0.9593, and 0.9022, and HD95 of 2.66, 1.72, 3.32 for the whole tumor, tumor core, and enhancing tumor, respectively.
Recent advances in artificial intelligence have enabled promising applications in neurosurgery that can enhance patient outcomes and minimize risks. This paper presents a novel system that utilizes AI to aid neurosurgeons in precisely identifying and localizing brain tumors. The system was trained on a dataset of brain MRI scans and utilized deep learning algorithms for segmentation and classification. Evaluation of the system on a separate set of brain MRI scans demonstrated an average Dice similarity coefficient of 0.87. The system was also evaluated through a user experience test involving the Department of Neurosurgery at the University Hospital Ulm, with results showing significant improvements in accuracy, efficiency, and reduced cognitive load and stress levels. Additionally, the system has demonstrated adaptability to various surgical scenarios and provides personalized guidance to users. These findings indicate the potential for AI to enhance the quality of neurosurgical interventions and improve patient outcomes. Future work will explore integrating this system with robotic surgical tools for minimally invasive surgeries.
Purpose
Artificial intelligence (AI), in particular deep learning (DL), has achieved remarkable results for medical image analysis in several applications. Yet the lack of human-like explanations of such systems is considered the principal restriction before utilizing these methods in clinical practice (Yang, Ye, & Xia, 2022).
Methods
Explainable Artificial Intelligence (XAI) provides a human-explainable and interpretable description of the “black-box” nature of DL (Gulum, Trombley, & Kantardzic, 2021). An effective XAI diagnosis generator, namely NeuroXAI (refer to Fig. 1), has been developed to extract 3D explanations from convolutional neural networks (CNN) models of brain gliomas (Zeineldin et al., 2022). By providing visual justification maps, NeuroXAI can help make DL models transparent and thus increase the trust of medical experts.
Results
NeuroXAI has been applied to two applications of the most widely investigated problems in brain imaging analysis, i.e. image classification and segmentation using magnetic resonance imaging (MRI). Visual attention maps of multiple XAI methods have been generated and compared for both applications, which could help to provide transparency about the performance of DL systems.
Conclusion
NeuroXAI helps to understand the prediction process of 3D CNN networks for brain glioma using human-understandable explanations. Results revealed that the investigated DL models behave in a logical human-like manner and can improve the analytical process of the MRI images systematically. Due to its open architecture, ease of implementation, and scalability to new XAI methods, NeuroXAI could be utilized to assist medical professionals in the detection and diagnosis of brain tumors. NeuroXAI code is publicly accessible at https://github.com/razeineldin/NeuroXAI
In the last decades, several driving systems were developed to improve the driving behaviour in energy efficiency or safety. However, these driving systems cover either the area of energy-efficiency or safety. Furthermore, they do not consider the stress level of the driver when showing a recommendation, although stress can lead to an unsafe or inefficient driving behaviour. In this paper, an approach is presented to consider the driver stress level in a driving system for safe and energy-efficient driving behaviour. The driving system tries to suppress a recommendation when the driver is in stress in order not to stress the driver additionally with recommendations in a stressful driving situation. This can lead to an increase in the road safety and in the user acceptance of the driving system, as the driver is not getting bothered or stressed by the driving system.
The evaluation of the approach showed, that the driving system
is able to show recommendations to the driver, while also reacting
to a high stress level by suppressing recommendations in
order not to stress the driver additionally.
Besides the optimisation of the car, energy-efficiency and safety can also be increased by optimising the driving behaviour. Based on this fact, a driving system is in development whose goal is to educate the driver in energy-efficient and safe driving. It monitors the driver, the car and the environment and gives energy-efficiency and safety relevant recommendations. However, the driving system tries not to distract or bother the driver by giving recommendations for example during stressful driving situations or when the driver is not interested in that recommendation. Therefore, the driving system monitors the stress level of the driver as well as the reaction of the driver to a given recommendation and decides whether to give a recommendation or not. This allows to suppress recommendations when needed and, thus, to increase the road safety and the user acceptance of the driving system.
Purpose: Human breath analysis is proposed with increasing frequency as a useful tool in clinical application. We performed this study to find the characteristic volatile organic compounds (VOCs) in the exhaled breath of patients with idiopathic pulmonary fibrosis (IPF) for discrimination from healthy subjects. Methods: VOCs in the exhaled breath of 40 IPF patients and 55 healthy controls were measured using a multi-capillary column and ion mobility spectrometer. The patients were examined by pulmonary function tests, blood gas analysis, and serum biomarkers of interstitial pneumonia. Results: We detected 85 VOC peaks in the exhaled breath of IPF patients and controls. IPF patients showed 5 significant VOC peaks; p-cymene, acetoin, isoprene, ethylbenzene, and an unknown compound. The VOC peak of p-cymene was significantly lower (p < 0.001), while the VOC peaks of acetoin, isoprene, ethylbenzene, and the unknown compound were significantly higher (p < 0.001 for all) compared with the peaks of controls. Comparing VOC peaks with clinical parameters, negative correlations with VC (r =−0.393, p = 0.013), %VC (r =−0.569, p < 0.001), FVC (r = −0.440, p = 0.004), %FVC (r =−0.539, p < 0.001), DLco (r =−0.394, p = 0.018), and %DLco (r =−0.413, p = 0.008) and a positive correlation with KL-6 (r = 0.432, p = 0.005) were found for p-cymene. Conclusion: We found characteristic 5 VOCs in the exhaled breath of IPF patients. Among them, the VOC peaks of p-cymene were related to the clinical parameters of IPF. These VOCs may be useful biomarkers of IPF.
This review gives a short overview of the physical processes involved in the formation of the polyelectrolyte multilayers (PEMs) and their destruction. These two processes are vital for the formation of PEMs with desired physical and chemical structures, and for loading them with active substances and their spatial controlled release. It includes a survey of the physical and chemical properties that are key points for controlling film nanostructure in relation to biological processes and different possibilities for controlling cell behavior by means of film composition, bioactivity, mechanical properties, and three-dimensional organization.
Rats are commonly used in medical research as they enable a high grade of standardization. The exhalome of ventilated rats has not as yet been investigated using an ion mobility spectrometer coupled with a multi-capillary column (MCC-IMS). As a first step, a rat model has to be established to measure potential biomarkers in the exhale with long-term settings, allowing constant and continuous analysis of exhaled air in time series. Therefore, eight animals were anaesthetized, prepared and ventilated for 1 h. A total of 73 peaks were directly detected with the IMS chromatogram. Thirty five of them were assigned to the ventilator system and 38 to the animals. Peak intensity varied within three measurements. The intensity of analytes of individual rats varied by a factor of up to 18. This new model will also enable continuous measurements of volatile organic compounds (VOCs) from rat's breath in long-term experiments. It is hoped that, in the future, variability and progression of VOCs can be monitored in different models of diseases using this set-up.
The metric and qualitative analysis of models of the upper and lower dental arches is an important aspect of orthodontic treatment planning. Currently available eLearning systems for dental education only allow access to digital learning materials, and do not interactively support the learning progress. Moreover, to date no study compared the efficiency of learning methods based on physical or digital study models. For this pilot study, 18 dental students were separated into two groups to investigate whether the learning success in study model analysis with an interactive elearning system is higher based on digital models or on conventional plaster models. The results show that with the digital method less time is needed per model analysis. Moreover, the digital approach leads to higher total scores than that based on plaster models. We conclude that interactive eLearning using digital dental arch models is a promising tool for dental education.
Diese Arbeit liefert einen Konzeptentwurf, der die Integration verschiedener Systeme mit prozessrelevanten klinischen Diensten gewährleistet. Chirurgische Abläufe werden in Form von Prozessen modelliert. Die Wahl der Notation und die Art der Modellierung dieser Prozesse spielt in der heutigen Forschung in diesem Gebiet eine zentrale Rolle. Sind diese Prozesse modelliert, besteht die Möglichkeit, diese in einer Workflow-Engine automatisiert auszuführen. Im Rahmen der Entwicklung eines Workflow-Managment-Systems stellt sich die Frage, wie die Anbindung dieser Workflow-Engine mit anderen Systemen erfolgen soll. In der Arbeit werden Schnittstellen abstrakt in der Web Services Description Language (WSDL) definiert. Darum werden automatisiert Artefakte erzeugt. Auf der Grundlage dieser Artefakte erfolgt die Integration der Systeme. Die Workflow-Engine kommunizieren über SOAP-Nachrichten (Simple Object Access Protocol) mit den entsprechenden Systemen. Dieser Ansatz wurde mithilfe eines Prototyps validiert und umgesetzt.
Purpose: Medical processes can be modeled using different methods and notations.Currently used modeling systems like Business Process Model and Notation (BPMN) are not capable of describing the highly flexible and variable medical processes in sufficient detail.
Methods: We combined two modeling systems, Business Process Management (BPM) and Adaptive Case Management (ACM), to be able to model non-deterministic medical processes. We used the new Standards Case Management Model and Notation (CMMN) and Decision Management Notation (DMN).
Results: First, we explain how CMMN, DMN and BPMN could be used to model non-deterministic medical processes. We applied this methodology to model 79 cataract operations provided by University Hospital Leipzig, Germany, and four cataract operations provided by University Eye Hospital Tuebingen, Germany. Our model consists of 85 tasks and about 20 decisions in BPMN. We were able to expand the system with more complex situations that might appear during an intervention.
Conclusion: An effective modeling of the cataract intervention is possible using the combination of BPM and ACM. The combination gives the possibility to depict complex processes with complex decisions. This combination allows a significant advantage for modeling perioperative processes.
Informationstechnische Systeme, die den Arbeitsablauf im klinischen Bereich unterstützen, sind aktuell auf organisatorische Abläufe beschränkt. Diese Arbeit stellt einen ersten Ansatz vor, wie solch ein System in den perioperativen Bereich eingebracht werden kann. Hierzu wurde eine Workflow Engine mit einer perioperativen Prozess-Visualisierung verknüpft. Das System wurde nach Modell-View-Controller-Prinzip implementiert. Als "Controller" kommt die Workflow Engine zum Einsatz; also "Modell" ein Prozessmodell, mit den erforderlichen klinischen Daten. Der "View" wurde durch eine abgekoppelte Anwendung realisiert, welche auf Web-Technologien basiert. Drei Visualisierungen, die Workflow Engine sowie die Anbindung beider über eine Datenbankschnittstelle, wurden erfolgreich umgesetzt. Bei den drei Visualisierungen wurden jeweils eine Ansicht für den OP-Koordinator, den Springer und eine Ansicht für die Übersicht einer OP erstellt.
Workflow driven support systems in the peri-operative area have the potential to optimize clinical processes and to allow new situation-adaptive support systems. We started to develop a workflow management system supporting all involved actors in the operating theatre with the goal to synchronize the tasks of the different stakeholders by giving relevant information to the right team members. Using the OMG standards BPMN, CMMN and DMN gives us the opportunity to bring established methods from other industries into the medical field. The system shows each addressed actor their information in the right place at the right time to make sure every member can execute their task in time to ensure a smooth workflow. The system has the overall view of all tasks. Accordingly, a workflow management system including the Camunda BPM workflow engine to run the models, and a middleware to connect different systems to the workflow engine and some graphical user interfaces to show necessary information or to interact with the system are used. The complete pipeline is implemented with a RESTful web service. The system is designed to include different systems like hospital information system (HIS) via the RESTful web service very easily and without loss of data. The first prototype is implemented and will be expanded.
An operation room is a stressful work environment. Nevertheless, all involved persons have to work safely as there is no space for making mistakes. To ensure a high level of concentration and seamless interaction, all involved persons have to know their own tasks and tasks of their colleagues. The entire team must work synchronously at all times. However, the operation room (OR) is a noisy environment and the actors have to set their focus on their work. To optimize the overall workflow, a task manager supporting the team was developed. Each actor is equipped with a client terminal showing a summary of their own tasks. Moreover, a big screen displays all tasks of all actors. The architecture is a distributed system based on a communication framework that supports the interaction of all clients with the task manager. A prototype of the task manager and several clients have been developed and implemented. The system represents a proof-of-concept for further development. This paper describes the concept of the task manager.
Durch das stetige Wachstum an neuen Technologien und Möglichkeiten steht der Verschmelzung von Technologien mit dem Menschen kaum noch etwas im Wege. Die Untersuchung der Implantate und die damit verbundenen Risiken sind ein Teil dieser Arbeit. Von Bedeutung sind hier die Funktionsweise und die IT-Sicherheitsaspekte. Alle in dieser Arbeit dargestellten Implantate benötigen eine Kommunikation nach außen. Diese Kommunikationsmöglichkeit birgt Risiken, die nicht nur auf die Daten der Träger beschränkt sind, sondern auch gesundheitliche Risiken beinhalten.
There have been substantial research efforts for algorithms to improve continuous and automated assessment of various health-related questions in recent years. This paper addresses the deployment gap between those improving algorithms and their usability in care and mobile health applications. In practice, most algorithms require significant and founded technical knowledge to be deployed at home or support healthcare professionals. Therefore, the digital participation of persons in need of health care professionals lacks a usable interface to use the current technological advances. In this paper, we propose applying algorithms taken from research as web-based microservices following the common approach of a RESTful service to bridge the gap and make algorithms accessible to caregivers and patients without technical knowledge and extended hardware capabilities. We address implementation details, interpretation and realization of guidelines, and privacy concerns using our self-implemented example. Also, we address further usability guidelines and our approach to those.
This paper presents a generic method to enhance performance and incorporate temporal information for cardiorespiratory-based sleep stage classification with a limited feature set and limited data. The classification algorithm relies on random forests and a feature set extracted from long-time home monitoring for sleep analysis. Employing temporal feature stacking, the system could be significantly improved in terms of Cohen’s κ and accuracy. The detection performance could be improved for three classes of sleep stages (Wake, REM, Non-REM sleep), four classes (Wake, Non-REM-Light sleep, Non-REM Deep sleep, REM sleep), and five classes (Wake, N1, N2, N3/4, REM sleep) from a κ of 0.44 to 0.58, 0.33 to 0.51, and 0.28 to 0.44 respectively by stacking features before and after the epoch to be classified. Further analysis was done for the optimal length and combination method for this stacking approach. Overall, three methods and a variable duration between 30 s and 30 min have been analyzed. Overnight recordings of 36 healthy subjects from the Interdisciplinary Center for Sleep Medicine at Charité-Universitätsmedizin Berlin and Leave-One-Out-Cross-Validation on a patient-level have been used to validate the method.
Functionally impaired people have problems with choosing and finding the right clothing. So, they need help in their daily life to wash and manage the clothing. The goal of this work is to support the user by giving recommendations to choose the right clothing, to find the clothing and how to wash the clothing. The idea behind eKlarA is to generate a gateway based system that uses sensors to identify the clothing and their state in the clothing cycle. The clothing cycle consists of (one and more) closet, laundry basket and washing machine in one or several places. The gateway uses the information about the clothing, weather and calendar to support the user in the different steps of the clothing cycle. This allows to give more freedom to the functionally impaired people in their daily life.
How to protect the skin from getting sun burnt? The sun can damage your skin e.g. skin cancer. But the sun has a positive effect to the human. The time in sun and the intensity are key values between enjoy the sunbath and having a negative effect to the skin. A smart device like a UV flower could help you to enjoy the sunbath. It measures the UV index around you and gives this information to a smartphone app. The development steps of such a device are described in this paper. The UV flower is made of textile fabrics.
Background
Personalized medicine requires the integration and analysis of vast amounts of patient data to realize individualized care. With Surgomics, we aim to facilitate personalized therapy recommendations in surgery by integration of intraoperative surgical data and their analysis with machine learning methods to leverage the potential of this data in analogy to Radiomics and Genomics.
Methods
We defined Surgomics as the entirety of surgomic features that are process characteristics of a surgical procedure automatically derived from multimodal intraoperative data to quantify processes in the operating room. In a multidisciplinary team we discussed potential data sources like endoscopic videos, vital sign monitoring, medical devices and instruments and respective surgomic features. Subsequently, an online questionnaire was sent to experts from surgery and (computer) science at multiple centers for rating the features’ clinical relevance and technical feasibility.
Results
In total, 52 surgomic features were identified and assigned to eight feature categories. Based on the expert survey (n = 66 participants) the feature category with the highest clinical relevance as rated by surgeons was “surgical skill and quality of performance” for morbidity and mortality (9.0 ± 1.3 on a numerical rating scale from 1 to 10) as well as for long-term (oncological) outcome (8.2 ± 1.8). The feature category with the highest feasibility to be automatically extracted as rated by (computer) scientists was “Instrument” (8.5 ± 1.7). Among the surgomic features ranked as most relevant in their respective category were “intraoperative adverse events”, “action performed with instruments”, “vital sign monitoring”, and “difficulty of surgery”.
Conclusion
Surgomics is a promising concept for the analysis of intraoperative data. Surgomics may be used together with preoperative features from clinical data and Radiomics to predict postoperative morbidity, mortality and long-term outcome, as well as to provide tailored feedback for surgeons.
The aim of this work was to investigate the mean fill weight control of a continuous capsule-filling process, whether it is possible to derive controller settings from an appendant process model. To that end, a system composed out of fully automated capsule filler and an online gravimetric scale was used to control the filled weight. This setup allows to examine challenges associated with continuous manufacturing processes, such as variations in the amount of active pharmaceutical ingredient (API) in the mixture due to fluctuations of the feeders or due to altered excipient batch qualities. Two types of controllers were investigated: a feedback control and a combination of feedback and feedforward control. Although both of those are common in the industry, determining the optimal parameter settings remains an issue. In this study, we developed a method to derive the control parameters based on process models in order to obtain optimal control for each filled product. Determined via rapid automated process development (RAPD), this method is an effective and fast way of determining control parameters. The method allowed us to optimize the weight control for three pharmaceutical excipients. By conducting experiments, we verified the feasibility of the proposed method and studied the dynamics of the controlled system. Our work provides important basic data on how capsule filler can be implemented into continuous manufacturing systems.
Background aims: In vitro engineered adipose tissue is in great demand to treat lost or damaged soft tissue or to screen for new drugs, among other applications.However, today most attempts depend on the use of animal-derived sera. To pave the way for the application of adipose tissue-engineered
products in clinical trials or as reliable and robust in vitro test systems, sera should be completely excluded from the production process. In this study, we aimed to develop an in vitro adipose tissue model in the absence of sera and maintain its function long-term.
Methods: Human adipose tissue-derived stem cells were expanded and characterized in a xeno- and serum-free environment. Adipogenic differentiation was induced using a completely defined medium. Developed adipocytes were maintained in a completely defined maturation medium for additional 28 days. In addition to cell-viability and adherence, adipocyte-specific markers such as perilipin A expression of leptin release were evaluated.
Results: The defined differentiation medium enhanced cell adherence and lipid
accumulation at a significant level compared with the corresponding negative control. The defined maturation medium also significantly supported cell adherence and functional adipocyte maturation during the long-term culture period.
Conclusions: The process described here enables functional adipocyte generation and maintenance without the addition fo unknown or unimal-derived constituents, achieving an important milestone in the introduction of adipose tissue engineered products into clinical trials or in vitro screening.
Completely defined co-culture of adipogenic differentiated ASCs and microvascular endothelial cells
(2018)
Vascularized adipose tissue models are in high demand as alternatives to animal models to elucidate the mechanisms of widespread diseases, screen for new drugs or assess drug safety levels. Animal-derived sera such as fetal bovine serum (FBS), which are commonly used in these models, are associated with ethical concerns, risk of contaminations and inconsistencies of their composition and impact on cells. In this study, we developed a serum-free, defined co culture medium and implemented it in an adipocyte/endothelial cell (EC) co culture model.
Human adipose-derived stem cells were differentiated under defined conditions (diffASCs) and, like human microvascular ECs (mvECs), cultured in a defined co culture medium in mono-, indirect or direct co-culture for 14 days. The defined co-culture medium was superior when compared to mono-culture media and facilitated the functional maintenance and maturation of diffASCs including perilipin A expression, lipid accumulation, and also glycerol and leptin release. The medium also allowed mvEC maintenance, confirmed by the expression of CD31 and von Willebrand factor (vWF), and by acetylated low density lipoprotein (acLDL) uptake. Thereby, mvECs showed strong dependence on EC-specific factors. Additionally, mvECs formed vascular structures in direct co-culture with diffASCs.
The completely defined co-culture system allows for the serum-free culture of adipocyte/EC co-cultures and thereby represents a valuable and ethically acceptable tool for the culture and study of vascularized adipose tissue models.
The field of breath analysis has developed to be of growing interest in medical diagnosis and patient monitoring. The main advantages are that it’s noninvasive, painless and repeatable in flexible cycles. Even though breath analysis is being researched for a couple of decades there are still many unanswered questions. Human breath contains volatile organic compounds which are emitted from inside the body. Some of these compounds can be assigned to specific sources, such as inflammation or cancer, but also to non health related origins. This paper gives an overview of breath analysis for the purpose of disease diagnosis and health monitoring. Therefore, literature regarding breath analysis in the medical field has been analyzed, from its early stages to the present. As a result, this paper gives an outline of the topic of breath analysis.
Type 1 diabetes is a chronic and a life threatening disease: an adjusted treatment and a proper management of the disease are crucial to prevent or delay the complications of diabetes. Although during the last decade the development of the artificial pancreas has presented great advances in diabetes care, the multiple daily injections therapy still represents the most widely used treatment option for type 1 diabetes. This work presents the proposal and first development stages of an application focused on guiding patients using the continuous glucose monitors and smart pens together with insulin and carbohydrates recommendations. Our proposal aims to develop a platform to integrate a series of innovative machine learning models and tools rigorously tested together with the use of the latest IoT devices to manage type 1 diabetes. The resulting system actually closes the loop, like the artificial pancreas, but in an intermittent way.
During two researches the influence of technologies on sleep were analyzed. The first one is about the effect of light on the circadian rhythm and as consequence on sleep quality of persons in a vegetative state. The second one, which is still running, surveys the influence of several technical tools on the sleep of elderly people living in a nursing home.
The imaging and force-distance curve modes of atomic force microscopy (AFM) are explored to compare the morphological and mechanical signatures of platelets from patients diagnosed with classical neurodegenerative diseases (NDDs) and healthy individuals. Our data demonstrate the potential of AFM to distinguish between the three NDDs-Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), and normal healthy platelets. The common features of platelets in the three pathologies are reduced membrane surface roughness, area and height, and enhanced nanomechanics in comparison with healthy cells. These changes might be related to general phenomena associated with reorganization in the platelet membrane morphology and cytoskeleton, a key factor for all platelets’ functions. Importantly, the platelets’ signatures are modified to a different extent in the three pathologies, most significant in ALS, less pronounced in PD and the least in AD platelets, which shows the specificity associated with each pathology. Moreover, different degree of activation, distinct pseudopodia and nanocluster formation characterize ALS, PD and AD platelets. The strongest alterations in the biophysical properties correlate with the highest activation of ALS platelets, which reflect the most significant changes in their nanoarchitecture. The specific platelet signatures that mark each of the studied pathologies can be added as novel biomarkers to the currently used diagnostic tools.
Die minimal-invasive Chirurgie (MIC) entwickelt sich durch den Einsatz von medizinischen Robotern wie dem da Vinci System von Intuitive Surgical stetig weiter. Hierdurch kann eine bessere oder gleichwertige Operation bei deutlich geringerer körperlicher Belastung des Operateurs erreicht werden. Dabei entstehen jedoch neue Problemstellungen wie beispielsweise Kollision zwischen Roboterarmen und die benötigte Zeit zum Einrichten einer geeigneten Roboterkonfiguration. Daher ist eine effiziente Vorbereitung und Planung der Interventionen erforderlich. Diese Arbeit präsentiert einen Ansatz für eine verbesserte Planung mit Augmented Reality (AR) und einer Robotik Simulationssoftware (RS). Die Robotik Simulation dient zur Berechnung einer Roboterkonfiguration unter Vorgabe der Port-Positionen. Augmented Reality wird verwendet, um die berechneten Pose in der realen Umgebung zu visualisieren und somit leichter in den Operationssaal zu übertragen.
Positively charged metallic oxides prevent blood coagulation whereas negatively charged metallic oxides are thrombogenic. This study was performed to examine whether this effect extends to metallic oxide nanoparticles. Oscillation shear rheometry was used to study the effect of zinc oxide and silicon dioxide nanoparticles on thrombus formation in human whole blood. Our data show that oscillation shear rheometry is a sensitive and robust technique to analyze thrombogenicity induced by nanoparticles. Blood without previous contact with nanoparticles had a clotting time (CT) of 16.7 ± 1.0 min reaching a maximal clot strength (CS) of 16 ± 14 Pa (G') after 30 min. ZnO nanoparticles (diameter 70 nm, +37 mV zeta-potential) at a concentration of 1 mg/mL prolonged CT to 20.8 ± 3.6 min and provoked a weak clot (CS 1.5 ± 1.0 Pa). However, at a lower concentration of 100 µg/mL the ZnO particles dramatically reduced CT to 6.0 ± 0.5 min and increased CS to 171 ± 63 Pa. This procoagulant effect decreased at lower concentrations reaching the detection limit at 10 ng/mL. SiO2 nanoparticles (diameter 232 nm, −28 mV zeta-potential) at high concentrations (1 mg/mL) reduced CT (2.1 ± 0.2 min) and stimulated CS (249 ± 59 Pa). Similar to ZnO particles, this procoagulant effect reached a detection limit at 10 ng/mL. Nanoparticles in high concentrations reproduce the surface charge effects on blood coagulation previously observed with large particles or solid metal oxides. However, nanoparticles with different surface charges equally well stimulate coagulation at lower concentrations. This stimulation may be an effect which is not directly related to the surface charge.
Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.
Die Erfindung betrifft einen Rollstuhl mit einem Gestell mit Rädern, einem Sitz sowie zwei gegenüber dem Sitz verlagerbaren Fußplatten und ein Trainingsgerät zur Bewegungstherapie der unteren Extremitäten einer in dem Rollstuhl sitzenden Person. Um das Trainingsgerät vereinfacht auszubilden, enthält das Trainingsgerät unabhängig von einer Fahrbewegung des Rollstuhls betreibbar eine an dem Gestell befestigbare, von einer Steuereinheit gesteuerte Elektromaschine, welche zur wechselweise erzwungenen Verlagerung der beiden Fußplatten mit den Fußplatten mechanisch gekoppelt ist.
Medical applications are becoming increasingly important in the current development of health care and therefore a crucial part of the medical industry. An essential component is the development of user interfaces for mobile medical applications. The conceptual process is crucial for the further development of the main development process. Inconsistency or errors in the conceptual phase, have a serious impact on all areas and could prevent the certification for market approval.
This paper presents a guide to support developer with this process. It was developed based on a requirement analysis of the legal requirements to publish a medical device.
The digital twin concept has been widely known for asset monitoring in the industry for a long time. A clear example is the automotive industry. Recently, there has also been significant interest in the application of digital twins in healthcare, especially in genomics in what is known as precision medicine. This work focuses on another medical speciality where digital twins can be applied, sleep medicine. However, there is still great controversy about the fundamentals that constitute digital twins, such as what this concept is based on and how it can be included in healthcare effectively and sustainably. This article reviews digital twins and their role so far in what is known as personalized medicine. In addition, a series of steps will be exposed for a possible implementation of a digital twin for a patient suffering from sleep disorders. For this, artificial intelligence techniques, clinical data management, and possible solutions for explaining the results derived from artificial intelligence models will be addressed.
Background: Polysomnography (PSG) is the gold standard for detecting obstructive sleep apnea (OSA). However, this technique has many disadvantages when using it outside the hospital or for daily use. Portable monitors (PMs) aim to streamline the OSA detection process through deep learning (DL).
Materials and methods: We studied how to detect OSA events and calculate the apnea-hypopnea index (AHI) by using deep learning models that aim to be implemented on PMs. Several deep learning models are presented after being trained on polysomnography data from the National Sleep Research Resource (NSRR) repository. The best hyperparameters for the DL architecture are presented. In addition, emphasis is focused on model explainability techniques, concretely on Gradient-weighted Class Activation Mapping (Grad-CAM).
Results: The results for the best DL model are presented and analyzed. The interpretability of the DL model is also analyzed by studying the regions of the signals that are most relevant for the model to make the decision. The model that yields the best result is a one-dimensional convolutional neural network (1D-CNN) with 84.3% accuracy.
Conclusion: The use of PMs using machine learning techniques for detecting OSA events still has a long way to go. However, our method for developing explainable DL models demonstrates that PMs appear to be a promising alternative to PSG in the future for the detection of obstructive apnea events and the automatic calculation of AHI.
The massive use of patient data for the training of artificial intelligence algorithms is common nowadays in medicine. In this scientific work, a statistical analysis of one of the most used datasets for the training of artificial intelligence models for the detection of sleep disorders is performed: sleep health heart study 2. This study focuses on determining whether the gender and age of the patients have a relevant influence to consider working with differentiated datasets based on these variables for the training of artificial intelligence models.
It has been widely shown that biomaterial surface topography can modulate host immune response, but a fundamental understanding of how different topographies contribute to pro-inflammatory or anti-inflammatory responses is still lacking. To investigate the impact of surface topography on immune response, we undertook a systematic approach by analyzing immune response to eight grades of medical grade polyurethane of increasing surface roughness in three in vitro models of the human immune system. Polyurethane specimens were produced with defined roughness values by injection molding according to the VDI 3400 industrial standard. Specimens ranged from 0.1 μm to 18 μm in average roughness (Ra), which was confirmed by confocal scanning microscopy. Immunological responses were assessed with THP-1-derived macrophages, human peripheral blood mononuclear cells (PBMCs), and whole blood following culture on polyurethane specimens. As shown by the release of pro-inflammatory and anti-inflammatory cytokines in all three models, a mild immune response to polyurethane was observed, however, this was not associated with the degree of surface roughness. Likewise, the cell morphology (cell spreading, circularity, and elongation) in THP-1-derived macrophages and the expression of CD molecules in the PBMC model on T cells (HLA-DR and CD16), NK cells (HLA-DR), and monocytes (HLA-DR, CD16, CD86, and CD163) showed no influence of surface roughness. In summary, this study shows that modifying surface roughness in the micrometer range on polyurethane has no impact on the pro-inflammatory immune response. Therefore, we propose that such modifications do not affect the immunocompatibility of polyurethane, thereby supporting the notion of polyurethane as a biocompatible material.
An ongoing challenge in our days is to lower the impact on the quality of life caused by dysfunctionality through individual support. With the background of an aging society and continuous increases in costs for care, a holistic solution is needed. This solution must integrate individual needs and preferences, locally available possibilities, regional conditions, professional and informal caregivers and provide the flexibility to implement future requirements. The proposed model is a result of a common initiative to overcome the major obstacles and to center a solution on individual needs caused by dysfunctionality.
Autism spectrum disorders (ASD) affect a large number of children both in the Russian Federation and in Germany. Early diagnosis is key for these children, because the sooner parents notice such disorders in a child and the rehabilitation and treatment program starts, the higher the likelihood of his social adaptation. The difficulties in raising such a child lie in the complexity of his learning outside of children's groups and the complexity of his medical care. In this regard, the development of digital applications that facilitate medical care and education of such children at home is important and relevant. The purpose of the project is to improve the availability and quality of healthcare and social adaptation at home of children with ASD through the use of digital technologies.
The goal of the presented project is to develop the concept of home e-health centers for barrier-free and cross-border telemedicine. AAL technologies are already present on the market but there is still a gap to close until they can be used for ordinary patient needs. The general idea needs to be accompanied by new services, which should be brought together in order to provide a full coverage of service for the users. Sleep and stress were chosen as predominant influence in the population. The executed scientific study of available home devices analyzing sleep has provided the necessary to select appropriate devices. The first choice for the project implementation is the device EMFIT QS+. This equipment provides a part of a complete system that a home telemedical hospital can provide at a level of precision and communication with internal and/or external health services.
Assistive environments are entering our homes faster than ever. However, there are still various barriers to be broken. One of the crucial points is a personalization of offered services and integration of assistive technologies in common objects and therefore in a regular daily routine. Recognition of sleep patterns for the preliminary sleep study is one of the Health services that could be performed in an undisturbing way. This article proposes the hardware system for the measurement of bio-vital signals necessary for initial sleep study in a nonobtrusive way. The first results confirm the potential of measurement of breathing and movement signals with the proposed system.
Measuring cardiorespiratory parameters in sleep, using non-contact sensors and the Ballistocardiography technique has received much attention due to the low-cost, unobtrusive, and non-invasive method. Designing a user-friendly, simple-to-use, and easy-to-deployment preserving less error-prone remains open and challenging due to the complex morphology of the signal. In this work, using four forcesensitive resistor sensors, we conducted a study by designing four distributions of sensors, in order to simplify the complexity of the system by identifying the region of interest for heartbeat and respiration measurement. The sensors are deployed under the mattress and attached to the bed frame without any interference with the subjects. The four distributions are combined in two linear horizontal, one linear vertical, and one square, covering the influencing region in cardiorespiratory activities. We recruited 4 subjects and acquired data in four regular sleeping positions, each for a duration of 80 seconds. The signal processing was performed using discrete wavelet transform bior 3.9 and smooth level of 4 as well as bandpass filtering. The results indicate that we have achieved the mean absolute error of 2.35 and 4.34 for respiration and heartbeat, respectively. The results recommend the efficiency of a triangleshaped structure of three sensors for measuring heartbeat and respiration parameters in all four regular sleeping positions.
Pharmaceutical companies are among the top investors into research and development (R&D) globally, as product innovation is still the main growth driver for the industry and because the related complexities necessitate enormous R&D investments. The market demand for new medicines to be more efficacious or to provide better safety than existing drugs and the regulatory need to prove superiority in clinical trials are reasons why drug R&D is increasingly expensive and pharmaceutical companies need to manage extraordinarily high costs per approved new compound.
We investigated the state of artificial intelligence (AI) in pharmaceutical research and development (R&D) and outline here a risk and reward perspective regarding digital R&D. Given the novelty of the research area, a combined qualitative and quantitative research method was chosen, including the analysis of annual company reports, investor relations information, patent applications, and scientific publications of 21 pharmaceutical companies for the years 2014 to 2019. As a result, we can confirm that the industry is in an ‘early mature’ phase of using AI in R&D. Furthermore, we can demonstrate that, despite the efforts that need to be managed, recent developments in the industry indicate that it is worthwhile to invest to become a ‘digital pharma player’.
Today, virtualizing pharma R&D is increasingly related with data analytics and artificial intelligence (AI), technologies that have been developed by software companies outside the healthcare sector. The process of virtualizing pharma R&D is closely related to the technological advancements that result in the generation of large data sets ranging from genomics, proteomics, metabolomics, medical imaging, IoT wearables and large clinical trials, making it necessary for pharma companies to find new ways to store and ultimately analyze information. As a consequence, pharma companies are experimenting with AI in R&D ranging from in-silico drug design to clinical trail participants identification or dosage error reduction.
Artificial intelligence (AI) technologies, such as machine learning or deep learning, have been predicted to highly impact future organizations and radically change the way how projects are managed. The Project Management Institute (PMI), the network of around 1.1 million certified project managers, ranked AI as one of the top three disruptors of their profession. In an own study on the effect of AI, 37% of the project management processes can be executed by machine learning and other AI technologies. In addition, Gartner recently postulated that 80% of the work of today's project managers may be eliminated by AI in 2030.
This editorial aims to outline today's project and portfolio management in context of pharmaceutical research and development (R&D), followed by an AI-vision and a more tangible mission, and illustrate what the consequences of an AI-enabled project and portfolio management could be for pharmaceutical R&D.