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1.
JMIR Res Protoc ; 13: e53627, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441925

RESUMO

BACKGROUND: Complex and expanding data sets in clinical oncology applications require flexible and interactive visualization of patient data to provide the maximum amount of information to physicians and other medical practitioners. Interdisciplinary tumor conferences in particular profit from customized tools to integrate, link, and visualize relevant data from all professions involved. OBJECTIVE: The scoping review proposed in this protocol aims to identify and present currently available data visualization tools for tumor boards and related areas. The objective of the review will be to provide not only an overview of digital tools currently used in tumor board settings, but also the data included, the respective visualization solutions, and their integration into hospital processes. METHODS: The planned scoping review process is based on the Arksey and O'Malley scoping study framework. The following electronic databases will be searched for articles published in English: PubMed, Web of Knowledge, and SCOPUS. Eligible articles will first undergo a deduplication step, followed by the screening of titles and abstracts. Second, a full-text screening will be used to reach the final decision about article selection. At least 2 reviewers will independently screen titles, abstracts, and full-text reports. Conflicting inclusion decisions will be resolved by a third reviewer. The remaining literature will be analyzed using a data extraction template proposed in this protocol. The template includes a variety of meta information as well as specific questions aiming to answer the research question: "What are the key features of data visualization solutions used in molecular and organ tumor boards, and how are these elements integrated and used within the clinical setting?" The findings will be compiled, charted, and presented as specified in the scoping study framework. Data for included tools may be supplemented with additional manual literature searches. The entire review process will be documented in alignment with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) flowchart. RESULTS: The results of this scoping review will be reported per the expanded PRISMA-ScR guidelines. A preliminary search using PubMed, Web of Knowledge, and Scopus resulted in 1320 articles after deduplication that will be included in the further review process. We expect the results to be published during the second quarter of 2024. CONCLUSIONS: Visualization is a key process in leveraging a data set's potentially available information and enabling its use in an interdisciplinary setting. The scoping review described in this protocol aims to present the status quo of visualization solutions for tumor board and clinical oncology applications and their integration into hospital processes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53627.

2.
BMJ Open ; 14(2): e074566, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38382948

RESUMO

BACKGROUND: The widespread use of electronic health records (EHRs) has led to a growing number of large routine primary care data collection projects globally, making these records a valuable resource for health services and epidemiological and clinical research. This scoping review aims to comprehensively assess and compare strengths and limitations of all German primary care data collection projects and relevant research publications that extract data directly from practice management systems (PMS). METHODS: A literature search was conducted in the electronic databases in May 2021 and in June 2022. The search string included terms related to general practice, routine data, and Germany. The retrieved studies were classified as applied studies and methodological studies, and categorised by type of research, subject area, sample of publications, disease category, or main medication analysed. RESULTS: A total of 962 references were identified, with 241 studies included from six German projects in which databases are populated by EHRs from PMS. The projects exhibited significant heterogeneity in terms of size, data collection methods, and variables collected. The majority of the applied studies (n = 205, 85%) originated from one database with a primary focus on pharmacoepidemiological topics (n = 127, 52%) including prescription patterns (n = 68, 28%) and studies about treatment outcomes, compliance, and treatment effectiveness (n = 34, 14%). Epidemiological studies (n = 77, 32%) mainly focused on incidence and prevalence studies (n = 41, 17%) and risk and comorbidity analysis studies (n = 31, 12%). Only 10% (n = 23) of studies were in the field of health services research, such as hospitalisation. CONCLUSION: The development and durability of primary care data collection projects in Germany is hindered by insufficient public funding, technical issues of data extraction, and strict data protection regulations. There is a need for further research and collaboration to improve the usability of EHRs for health services and research.


Assuntos
Registros Eletrônicos de Saúde , Atenção Primária à Saúde , Humanos , Coleta de Dados , Comorbidade , Estudos Transversais
3.
JMIR Med Inform ; 11: e50017, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38079196

RESUMO

BACKGROUND: In molecular tumor boards (MTBs), patients with rare or advanced cancers are discussed by a multidisciplinary team of health care professionals. Software support for MTBs is lacking; in particular, tools for preparing and documenting MTB therapy recommendations need to be developed. OBJECTIVE: We aimed to implement an extension to cBioPortal to provide a tool for the documentation of therapy recommendations from MTB sessions in a secure and standardized manner. The developed extension should be embedded in the patient view of cBioPortal to enable easy documentation during MTB sessions. The resulting architecture for storing therapy recommendations should be integrable into various hospital information systems. METHODS: On the basis of a requirements analysis and technology analysis for authentication techniques, a prototype was developed and iteratively refined through a user-centered development process. In conclusion, the tool was evaluated via a usability evaluation, including interviews, structured questionnaires, and the System Usability Scale. RESULTS: The patient view of cBioPortal was extended with a new tab that enables users to document MTB sessions and therapy recommendations. The role-based access control was expanded to allow for a finer distinction among the rights to view, edit, and delete data. The usability evaluation showed overall good usability and a System Usability Scale score of 83.57. CONCLUSIONS: This study demonstrates how cBioPortal can be extended to not only visualize MTB patient data but also be used as a documentation platform for therapy recommendations.

5.
Stud Health Technol Inform ; 307: 102-109, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37697843

RESUMO

BACKGROUND: The number of emergency medical service (EMS) calls in Germany is continuously increasing. The initial assessment, the pre-hospital care and the choice of hospital for further care by the EMS influences the patient's outcome and are the basis for further care in hospital. However, the EMS does not receive any official feedback on its decisions. OBJECTIVES: This study evaluates the demand for a feedback system from the emergency department (ED) to the EMS, what it should contain, and how it could be integrated in the electronic clinical systems. METHODS: A semi-structured interview guideline for expert interviews with members of EMS staff (n = 6) and ED staff (n = 17) was developed. A mockup to visualise a possible implementation was designed and included in the interview. RESULTS: There is a significant demand for feedback on pre-diagnosis, pre-hospital care and handover of patients from the EMS to the ED. The EDs are very interested in improving the collaboration with the paramedic services through feedback. CONCLUSION: A feedback system is strongly desired by various EMS stakeholders and, according to them, could improve both EMS and ED collaboration and overall patient care.


Assuntos
Serviços Médicos de Emergência , Auxiliares de Emergência , Humanos , Retroalimentação , Serviço Hospitalar de Emergência , Hospitais
6.
Stud Health Technol Inform ; 307: 110-116, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37697844

RESUMO

BACKGROUND: In Germany, patients are entitled to a medication plan. While the overview is useful, it does not contain explicit information on various potential adverse drug events (ADEs). Therefore, physicians must continue to seek information from various sources to ensure medication safety. OBJECTIVE: In this project a first functional prototype of a medication therapy tool was developed that focuses on visualizing and highlighting potential ADEs. A usability analysis about the tool's functionality, design and usability was conducted. METHODS: A web application tool was developed using the MMI Pharmindex as database. ADEs are color coded and can be displayed in three different ways - as a list, a table, or a graph. To test the tool, an online survey was conducted amongst healthcare professionals (n = 9). The test included two real medication plans to check ADEs through the tool. RESULTS: The survey results indicated that the web tool was clear and self-explanatory. It scored overall "good" (score: 76.5) on the System Usability Scale questionnaire. Due to the free-text information of the database used, there were some inconsistencies in the visualized ADEs. CONCLUSION: There is a demand for a visualization tool for medications. The high quality of the database is crucial in order to correctly visualize all necessary information, such as drug-drug interactions and inclusion of patient data. This is essential to provide a trustworthy tool for medical professionals.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Bases de Dados Factuais , Alemanha , Pessoal de Saúde , Decoração de Interiores e Mobiliário
7.
Cancers (Basel) ; 15(13)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37444566

RESUMO

(1) Background: Next-generation sequencing (NGS) of patients with advanced tumors is becoming an established method in Molecular Tumor Boards. However, somatic variant detection, interpretation, and report generation, require in-depth knowledge of both bioinformatics and oncology. (2) Methods: MIRACUM-Pipe combines many individual tools into a seamless workflow for comprehensive analyses and annotation of NGS data including quality control, alignment, variant calling, copy number variation estimation, evaluation of complex biomarkers, and RNA fusion detection. (3) Results: MIRACUM-Pipe offers an easy-to-use, one-prompt standardized solution to analyze NGS data, including quality control, variant calling, copy number estimation, annotation, visualization, and report generation. (4) Conclusions: MIRACUM-Pipe, a versatile pipeline for NGS, can be customized according to bioinformatics and clinical needs and to support clinical decision-making with visual processing and interactive reporting.

8.
Vaccines (Basel) ; 11(6)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37376412

RESUMO

Cancer neoantigens that arise from somatic mutations have emerged as important targets for personalized immunization. Here, we report an improved overall survival of a HER2-positive metastatic breast cancer patient using a bioinformatic-based personalized peptide immunization called BITAP (BioInformatic Tumor Address Peptides). The epitopes were predicted using our in-house bioinformatic pipeline, and the immunogenicity was tested by IFN-γ ELISPOT and intracellular cytokine staining assays. In total, a significant peptide-specific T-cell response was detected against 18 out of the 76 (≈24%) tested peptides. The patient's follow-up by measuring serologic markers showed a significant reduction in the tumor marker levels following BITAP immunization. Along with standard treatment, the patient treated with the BITAP showed stable disease with a remarkably improved overall survival, and no serious treatment-related adverse effects. In conclusion, our findings suggest that BITAP immunization is feasible, and safe, and may induce tumor regressions in patients with HER2-positive subsets of breast cancer.

9.
Int J Mol Sci ; 24(9)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37175428

RESUMO

Mechanosensing plays an essential role in maintaining tissue functions. Across the human body, several tissues (i.e., striated muscles, bones, tendons, ligaments, as well as cartilage) require mechanical loading to exert their physiological functions. Contrary, mechanical unloading triggers pathological remodeling of these tissues and, consequently, human body dysfunctions. At the cellular level, both mechanical loading and unloading regulate a wide spectrum of cellular pathways. Among those, pathways regulated by oxidants such as reactive oxygen species (ROS) represent an essential node critically controlling tissue organization and function. Hence, a sensitive balance between the generation and elimination of oxidants keeps them within a physiological range. Here, the Nuclear Factor-E2-related factor 2/Antioxidant response element (Nrf2/ARE) system plays an essential role as it constitutes the major cellular regulation against exogenous and endogenous oxidative stresses. Dysregulations of this system advance, i.a., liver, neurodegenerative, and cancer diseases. Herein, we extend our comprehension of the Nrf2 system to the aforementioned mechanically sensitive tissues to explore its role in their physiology and pathology. We demonstrate the relevance of it for the tissues' functionality and highlight the imperative to further explore the Nrf2 system to understand the physiology and pathology of mechanically sensitive tissues in the context of redox biology.


Assuntos
Elementos de Resposta Antioxidante , Fator 2 Relacionado a NF-E2 , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Mecanotransdução Celular , Fator 2 Relacionado a NF-E2/metabolismo , Oxidantes , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
10.
Artigo em Alemão | MEDLINE | ID: mdl-37079066

RESUMO

The Beobachtungspraxennetzwerk Halle (BeoNet-Halle) is an innovative database of outpatient care that has been collecting patient data from participating primary care and specialty practices throughout Germany since 2020 and making it available for research and care. The database is set up and maintained by the Institute of Medical Epidemiology, Biometrics and Informatics and the Institute of General Practice and Family Medicine of the Martin Luther University Halle-Wittenberg. Furthermore, the Data Integration Center of the University Medical Center Halle is involved in the project. In principle, anonymized and pseudonymized patient data from all commercially available practice management systems should flow into the databases.In this article, we describe the structure and methods of the multi-purpose database BeoNet and quantify the current data stock. The workflow of collection, transfer, and storage of broad consents is described and advantages and limitations of the database are discussed.BeoNet-Halle currently contains anonymized data of approximately 73,043 patients from five physician practices. Furthermore, it includes data from more than 2,653,437 ICD-10 diagnoses, 1,403,726 prescriptions, and 1,894,074 laboratory results. Pseudonymized data were successfully exported from 481 patients.BeoNet-Halle enables an almost seamless representation of the care provided in the participating practices. In the future, the database will map patient treatment pathways across practices and provide high-quality care data to contribute to health policy decision-making and optimization of care processes.


Assuntos
Medicina Geral , Clínicos Gerais , Humanos , Alemanha , Centros Médicos Acadêmicos , Atenção à Saúde
11.
J Appl Clin Med Phys ; 24(8): e13985, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37051765

RESUMO

The gamma analysis metric is a commonly used metric for VMAT plan evaluation. The major drawback of this is the lack of correlation between gamma passing rates and DVH values. The novel GDSAmean metric was developed by Steers et al. to quantify changes in the PTV mean dose (Dmean ) for VMAT patients. The aim of this work is to apply the GDSA retrospectively on head-and-neck cancer patients treated on the newly acquired Varian Halcyon, to assess changes in GDSAmean , and to evaluate the cause of day-to-day changes in the time-plot series. In-vivo EPID transmission images of head-and-neck cancer patients treated between August 2019 and July 2020 were analyzed retrospectively. The GDSAmean was determined for all patients treated. The changes in patient anatomy and rotational errors were quantified using the daily CBCT images and added to a time-plot with the daily change in GDSAmean . Over 97% of the delivered treatment fractions had a GDSAmean  < 3%. Thirteen of the patients received at least one treatment fraction where the GDSAmean  > 3%. Most of these deviations occurred for the later fractions of radiotherapy treatment. Additionally, 92% of these patients were treated for malignancies involving the larynx and oropharynx. Notable deviations in the effective separation diameters were observed for 62% of the patients where the change in GDSAmean  > 3%. For the other five cases with GDSAmean  < 3%, the mean pitch, roll, and yaw rotational errors were 0.90°, 0.45°, and 0.43°, respectively. A GDSAmean  > 3% was more likely due to a change in separation, whereas a GDSAmean  < 3% was likely caused by rotational errors. Pitch errors were shown to be the most dominant. The GDSAmean is easily implementable and can aid in scheduling new CT scans for patients before significant deviations in dose delivery occur.


Assuntos
Neoplasias de Cabeça e Pescoço , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia
12.
Antioxidants (Basel) ; 12(3)2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36979025

RESUMO

Nuclear factor erythroid 2-related factor 2 (Nrf2) is downregulated in chronic kidney disease (CKD). Activation of Nrf2 might be a therapeutic option in CKD. Here we investigate the effect of Nrf2 activation on aldosterone (Aldo)-induced renal injury. Wild-type (WT) mice, transgenic Keap1 hypomorphic (Nrf2ꜛ, genotype results in upregulation of Nrf2 expression) mice and WT mice treated with the Nrf2 activator sulforaphane (Sulf) received Aldo for 4 weeks. In Aldo-treated mice, kidneys were significantly heavier and pathologically altered, reflected by increased urinary albumin levels and tissue damage. In Nrf2ꜛ-Aldo mice the tubule damage marker NGAL was significantly decreased. Increased oxidative damage markers (8-OHdG, 15-isoprostane F2t) were measured in all Aldo-treated groups. Aldo-increased Nrf2 amounts were mainly found in the late tubule system. The amount of phosphorylated and thus putatively active Nrf2 was significantly increased by Aldo only in WT mice. However, expression of Nrf2 target genes NQO1 and HO1 was decreased in all Aldo-infused mice. GSK3ß, which promotes Nrf2 degradation, was significantly increased in the kidneys of Aldo-treated WT mice. Neither genetic nor pharmacological Nrf2 activation was able to prevent oxidative injury induced by Aldo, probably due to induction of negative regulators of Nrf2.

13.
J Physiol ; 601(8): 1353-1370, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36866700

RESUMO

Optical mapping is a widely used tool to record and visualize the electrophysiological properties in a variety of myocardial preparations such as Langendorff-perfused isolated hearts, coronary-perfused wedge preparations, and cell culture monolayers. Motion artifact originating from the mechanical contraction of the myocardium creates a significant challenge to performing optical mapping of contracting hearts. Hence, to minimize the motion artifact, cardiac optical mapping studies are mostly performed on non-contracting hearts, where the mechanical contraction is removed using pharmacological excitation-contraction uncouplers. However, such experimental preparations eliminate the possibility of electromechanical interaction, and effects such as mechano-electric feedback cannot be studied. Recent developments in computer vision algorithms and ratiometric techniques have opened the possibility of performing optical mapping studies on isolated contracting hearts. In this review, we discuss the existing techniques and challenges of optical mapping of contracting hearts.


Assuntos
Coração , Miocárdio , Potenciais de Ação/fisiologia , Coração/diagnóstico por imagem , Coração/fisiologia
14.
Phys Rev E ; 107(1-1): 014221, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36797900

RESUMO

Scroll wave dynamics are thought to underlie life-threatening ventricular fibrillation. However, direct observations of three-dimensional electrical scroll waves remain elusive, as there is no direct way to measure action potential wave patterns transmurally throughout the thick ventricular heart muscle. Here we study whether it is possible to reconstruct simulated scroll waves and scroll wave chaos using deep learning. We trained encoding-decoding convolutional neural networks to predict three-dimensional scroll wave dynamics inside bulk-shaped excitable media from two-dimensional observations of the wave dynamics on the bulk's surface. We tested whether observations from one or two opposing surfaces would be sufficient and whether transparency or measurements of surface deformations enhances the reconstruction. Further, we evaluated the approach's robustness against noise and tested the feasibility of predicting the bulk's thickness. We distinguished isotropic and anisotropic, as well as opaque and transparent, excitable media as models for cardiac tissue and the Belousov-Zhabotinsky chemical reaction, respectively. While we demonstrate that it is possible to reconstruct three-dimensional scroll wave dynamics, we also show that it is challenging to reconstruct complicated scroll wave chaos and that prediction outcomes depend on various factors such as transparency, anisotropy, and ultimately the thickness of the medium compared to the size of the scroll waves. In particular, we found that anisotropy provides crucial information for neural networks to decode depth, which facilitates the reconstructions. In the future, deep neural networks could be used to visualize intramural action potential wave patterns from epi- or endocardial measurements.


Assuntos
Arritmias Cardíacas , Coração , Humanos , Coração/fisiologia , Miocárdio , Ventrículos do Coração , Redes Neurais de Computação
15.
Gastroenterology ; 164(3): 392-406.e5, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36402190

RESUMO

BACKGROUND & AIMS: Advanced colorectal carcinoma (CRC) is characterized by a high frequency of primary immune evasion and refractoriness to immunotherapy. Given the importance of interferon (IFN)-γ in CRC immunosurveillance, we investigated whether and how acquired IFN-γ resistance in tumor cells would promote tumor growth, and whether IFN-γ sensitivity could be restored. METHODS: Spontaneous and colitis-associated CRC development was induced in mice with a specific IFN-γ pathway inhibition in intestinal epithelial cells. The influence of IFN-γ pathway gene status and expression on survival was assessed in patients with CRC. The mechanisms underlying IFN-γ resistance were investigated in CRC cell lines. RESULTS: The conditional knockout of the IFN-γ receptor in intestinal epithelial cells enhanced spontaneous and colitis-associated colon tumorigenesis in mice, and the loss of IFN-γ receptor α (IFNγRα) expression by tumor cells predicted poor prognosis in patients with CRC. IFNγRα expression was repressed in human CRC cells through changes in N-glycosylation, which decreased protein stability via proteasome-dependent degradation, inhibiting IFNγR-signaling. Downregulation of the bisecting N-acetylglucosaminyltransferase III (MGAT3) expression was associated with IFN-γ resistance in all IFN-γ-resistant cells, and highly correlated with low IFNγRα expression in CRC tissues. Both ectopic and pharmacological reconstitution of MGAT3 expression with all-trans retinoic acid increased bisecting N-glycosylation, as well as IFNγRα protein stability and signaling. CONCLUSIONS: Together, our results demonstrated that tumor-associated changes in N-glycosylation destabilize IFNγRα, causing IFN-γ resistance in CRC. IFN-γ sensitivity could be reestablished through the increase in MGAT3 expression, notably via all-trans retinoic acid treatment, providing new prospects for the treatment of immune-resistant CRC.


Assuntos
Colite , Neoplasias Colorretais , Humanos , Camundongos , Animais , Glicosilação , Neoplasias Colorretais/patologia , Interferon gama , Imunoterapia , Colite/patologia , Tretinoína
16.
Europace ; 25(2): 688-697, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35989424

RESUMO

AIMS: Cardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood. METHODS AND RESULTS: Ventricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity. CONCLUSION: RT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients.


Assuntos
Arritmias Cardíacas , Músculos Papilares , Animais , Ovinos , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/etiologia , Ventrículos do Coração , Potenciais de Ação/fisiologia , Eletrocardiografia
17.
BMC Musculoskelet Disord ; 23(1): 1015, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434613

RESUMO

BACKGROUND: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial transcription factor for cellular redox homeostasis. The association of Nrf2 with elderly female osteoporotic has yet to be fully described. The aim was to elucidate a potential age-dependent Nrf2 contribution to female osteoporosis in mice. METHODS: Eighteen female wild type (WT) and 16 Nrf2-knockout (KO) mice were sacrificed at different ages (12 weeks = young mature adult and 90 weeks = old) to analyze their femurs. The morphological properties (trabecular and cortical) were evaluated by micro-computed tomography (µCT) and compared to gold standard histochemistry analysis. The quasi-static compression tests were performed to calculate the mechanical properties of bones. Additionally, the population of bone resorbing cells and aromatase expression by osteocytes was immunohistochemically evaluated and empty osteocyte lacunae was counted in cortical bone. RESULTS: Old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness, cortical area, and bone fraction compared to old WT mice, regardless of no significant difference in skeletally mature young adult mice between WT and KO. Specifically, while all old WT mice showed thin metaphyseal trabeculae, trabecular bone was completely absent in 60% of old KO mice. Additionally, old KO mice showed significantly more osteoclast-like cells and fewer aromatase-positive osteocytes than WT mice, whereas the occurrence of empty osteocyte lacunae did not differ between both groups. Nrf2-KO mice further showed an age-dependently reduced fracture resilience compared to age-matched WT mice. CONCLUSION: Our results suggest that chronic Nrf2 loss can lead to age-dependent progression of female osteoporosis.


Assuntos
Fator 2 Relacionado a NF-E2 , Osteoporose , Feminino , Camundongos , Animais , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Aromatase , Microtomografia por Raio-X , Camundongos Endogâmicos C57BL , Osteoporose/diagnóstico por imagem , Osteoporose/genética , Osteoporose/metabolismo , Camundongos Knockout
18.
Redox Biol ; 57: 102453, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36209041

RESUMO

The Nrf2 signaling pathway prevents cancer initiation, but genetic mutations that activate this pathway are found in various types of cancer. The molecular mechanisms underlying this Janus-headed character are still not understood. Here, we show that sustained Nrf2 activation induces proliferation and dedifferentiation of a Wnt-responsive perivenular hepatic progenitor cell population, transforming them into metastatic cancer cells. The neoplastic lesions display many histological features known from human hepatoblastoma. We describe an Nrf2-induced upregulation of ß-catenin expression and its activation as the underlying mechanism for the observed malignant transformation. Thus, we have identified the Nrf2-ß-catenin axis promoting proliferation of hepatic stem cells and triggering tumorigenesis. These findings support the concept that different functional levels of Nrf2 control both the protection against various toxins as well as liver regeneration by activating hepatic stem cells. Activation of the hepatic stem cell compartment confers the observation that unbridled Nrf2 activation may trigger tumorigenesis.


Assuntos
Neoplasias Hepáticas , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Células-Tronco/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Neoplasias Hepáticas/metabolismo , Proliferação de Células
19.
Front Cardiovasc Med ; 9: 787627, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686036

RESUMO

Optical mapping of action potentials or calcium transients in contracting cardiac tissues are challenging because of the severe sensitivity of the measurements to motion. The measurements rely on the accurate numerical tracking and analysis of fluorescence changes emitted by the tissue as it moves, and inaccurate or no tracking can produce motion artifacts and lead to imprecise measurements that can prohibit the analysis of the data. Recently, it was demonstrated that numerical motion-tracking and -stabilization can effectively inhibit motion artifacts, allowing highly detailed simultaneous measurements of electrophysiological phenomena and tissue mechanics. However, the field of electromechanical optical mapping is still young and under development. To date, the technique is only used by a few laboratories, the processing of the video data is time-consuming and performed offline post-acquisition as it is associated with a considerable demand for computing power. In addition, a systematic review of numerical motion tracking algorithms applicable to optical mapping data is lacking. To address these issues, we evaluated 5 open-source numerical motion-tracking algorithms implemented on a graphics processing unit (GPU) and compared their performance when tracking and compensating motion and measuring optical traces in voltage- or calcium-sensitive optical mapping videos of contracting cardiac tissues. Using GPU-accelerated numerical motion tracking, the processing times necessary to analyze optical mapping videos become substantially reduced. We demonstrate that it is possible to track and stabilize motion and create motion-compensated optical maps in real-time with low-resolution (128 x 128 pixels) and high resolution (800 x 800 pixels) optical mapping videos acquired at 500 and 40 fps, respectively. We evaluated the tracking accuracies and motion-stabilization capabilities of the GPU-based algorithms on synthetic optical mapping videos, determined their sensitivity to fluorescence signals and noise, and demonstrate the efficacy of the Farnebäck algorithm with recordings of contracting human cardiac cell cultures and beating hearts from 3 different species (mouse, rabbit, pig) imaged with 4 different high-speed cameras. GPU-accelerated processing provides a substantial increase in processing speed, which could open the path for more widespread use of numerical motion tracking and stabilization algorithms during routine optical mapping studies.

20.
Stud Health Technol Inform ; 294: 68-72, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35612018

RESUMO

BACKGROUND: Artificial intelligence (AI) in medicine is a very topical issue. As far as the attitudes and perspectives of the different stakeholders in healthcare are concerned, there is still much to be explored. OBJECTIVE: Our aim was to determine attitudes and aspects towards acceptance of AI applications from the perspective of physicians in university hospitals. METHODS: We conducted individual exploratory expert interviews. Low fidelity mockups were used to show interviewees potential application areas of AI in clinical care. RESULTS: In principle, physicians are open to the use of AI in medical care. However, they are critical of some aspects such as data protection or the lack of explainability of the systems. CONCLUSION: Although some trends in attitudes e.g., on the challenges or benefits of using AI became clear, it is necessary to conduct further research as intended by the subsequent PEAK project.


Assuntos
Inteligência Artificial , Médicos , Atitude , Atenção à Saúde , Humanos , Assistência ao Paciente
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