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Reliability and validity of the German “Evidence-Based Practice Confidence (EPIC) Scale” for allied health professionals
No full textDiscovery of a Noncompetitive Open-Flap Selective Inhibitor of Plasmepsin II with Antiplasmodial Activity
No full textInhibition of the Parkinson’s Disease-Related Protein DJ-1 by Endogenous Neurotoxins of the 1,2,3,4-Tetrahydroisoquinoline Family
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Segment Anything for Microscopy
No full textAbstract Accurate segmentation of objects in microscopy images remains a bottleneck for many researchers despite the number of tools developed for this purpose. Here, we present Segment Anything for Microscopy (μSAM), a tool for segmentation and tracking in multidimensional microscopy data. It is based on Segment Anything, a vision foundation model for image segmentation. We extend it by fine-tuning generalist models for light and electron microscopy that clearly improve segmentation quality for a wide range of imaging conditions. We also implement interactive and automatic segmentation in a napari plugin that can speed up diverse segmentation tasks and provides a unified solution for microscopy annotation across different microscopy modalities. Our work constitutes the application of vision foundation models in microscopy, laying the groundwork for solving image analysis tasks in this domain with a small set of powerful deep learning models
Real-world smartphone-based point-of-care diagnostics in primary health care to monitor HbA1c levels in people with diabetes
No full textAbstract Background The lack of accurate and affordable monitoring of glycated hemoglobin (HbA1c) is a common issue among patients with diabetes in low- and middle-income countries. We aimed to test a tablet- and smartphone-based point-of-care (TSB POC) device against a local laboratory-based measure of HbA1c for monitoring diabetes under real-world conditions. Methods For this cross-sectional clinical method applicability study, capillary and venous blood was collected in duplicate and analyzed at local primary health care centers. For a heterogeneity test, the tests were performed by an expert, and by a team of local nurses. The study was conducted in a multicenter design in rural and urban Aceh, Indonesia in 2019, and included a total of 533 adults. We mainly used Bland-Altman plots to assess the number of readings within the 95%-limits of agreement (LoA) and Deming regressions. Results The results show a mean difference between capillary HbA1c on the test device and the reference method of −0.54 [CI 0.95 = −1.6933; 0.6048] with 5.21% of measurements outside the LoA and a Pearson’s r = 0.91 in the Deming Regression. There is no significant difference in test concordance between local nurses and the expert (4.23% versus 5.13% results outside the LoA [CI 0.95 = −0.0331; 0.0511]). Conclusions TSB POC for analysis of HbA1c is an acceptable alternative for accessible monitoring of diabetes patients under these conditions. This method could provide access to high-quality diagnostic decisions through regular and cost-effective HbA1c monitoring directly in healthcare facilities, thus providing better access to essential health services
Functional apoptosis profiling reveals vulnerabilities in T-cell large granular lymphocytic leukemia
No full textAbstract T-cell large granular lymphocytic leukemia (T-LGLL) is a rare hematologic neoplasm characterized by clonal expansion of CD3 + cytotoxic T lymphocytes and a highly heterogeneous clinical course. Conventional therapy primarily includes immunosuppressive regimen. However, optimal front-line approaches still need to be defined and refractory disease remains a clinical challenge. Thus, we here aimed to explore functional dependencies of T-LGLL as a basis for personalized therapeutic strategies. We performed functional apoptosis profiling and ex vivo drug treatment in a series of 8 clinically and genetically characterized T-LGLL patients from two German University hospitals. Our series of patients underscored the clinical and genetic heterogeneity of the disease. Genetically, only 2 patients harbored a STAT3 mutation. To identify targetable anti-apoptotic mechanisms, we performed selective functional BH3 profiling on the patients’ CD8 + T-cells harboring the malignant T-LGLL cells versus the same patients’ normal CD4 + T-cells. CD8 + cells in 50% of the patients (4/8) demonstrated a dominant functional dependence on MCL-1 as compared to the same patients’ normal T-cells. Accordingly, CD8 + T-LGLL cells from patients with enhanced MCL1 dependence significantly responded to AZD-5991 ex vivo while no response was observed in the remaining samples lacking enhanced MCL-1 dependence. Across clinically and genetically heterogeneous cases of T-LGLL, functional apoptosis profiling identified patients with CD8 + T-LGLL cells harboring a dominant dependence on MCL-1 as a potential therapeutic target.Open-Access-Publikationsfonds 202
Vision Restoration through transorbital electrical stimulation in Optic Neuropathy in patients with significant optic atrophy due to primary open-angle glaucoma—a randomised, controlled, double-blind, multicentre clinical trial: the VIRON study protocol
No full textIntroduction Glaucoma is one of the most common causes of blindness and affects more than 70 million people worldwide. The disease is characterised by the loss of retinal ganglion cells associated with a progressive optic neuropathy, resulting in an impairment of visual functions, for example, visual field loss. Nowadays, the only modifiable risk factor is the increase in intraocular pressure, and its treatment is to lower this pressure by medication, laser treatment or surgery to avoid disease progression. New methods for preventing and reversing vision loss are thus urgently needed. Several small and two multicentre studies have presented evidence that repetitive transorbital alternating current stimulation (rtACS) can lead to long-lasting visual field improvement. This could open a new and inexpensive therapeutic option for optic atrophy. However, the level of evidence for this method is still fairly rather poor, and further trials are needed. Therefore, this clinical trial aims to prove the effectiveness of rtACS compared with sham stimulation in patients with primary open-angle glaucoma (POAG). Methods and analysis VIRON (Vision Restoration in Optic Neuropathy) is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with three arms. The primary objective is to assess the effectiveness of rtACS in patients with POAG compared with sham stimulation. The primary outcome is the change in mean defect (MD) in the visual field immediately after 10 sessions of rtACS (days 9, 16 and 23) compared with the values of initial perimetry (days −21 to –14 and 0) after applying electrical stimulation with a classical montage, compared with sham and electrical stimulation using individualised montage. Secondary outcome measures comprise a long-term effect with changes in MD at 24 weeks after stimulation, and data from the National Eye Institute Visual Function-25 and quality of life (Short Form 36) questionnaires. The target population are patients with glaucomatous optic atrophy and significant glaucomatous visual field defects (MD of 5–22 dB) due to POAG. After randomisation, patients received either classical rtACS (group 1), individual rtACS (group 2) or sham stimulation (group 3) in daily 25 min stimulation sessions in two series of five consecutive days separated by a weekend interval. In group 1, active stimulation will be via the routinely applied montage using two electrodes affixed on the right and left side of the head, next to the eyes, with straightforward fixation. In group 2, the current flow will be individually modelled (MRI-based) to target areas of partial visual field defects by optimising electrode positions in conjunction with an optimised visual fixation direction. Group 3 with sham stimulation will serve as control. The calculated sample size required to achieve a statistical power of 80% for a relevant effect size and allow for dropouts was 300 (100 per group). The trial has already begun with the first patient in July 2023. The planned recruitment period is 24 months with an estimated end of the study in November 2025 (last patient out). An adjusted extension of the study period is planned. Ethics and dissemination VIRON was approved by the Central Ethics Committee of the University Medical Center Göttingen (19 October 2022) and those of the individual participating centres (Bonn: 446/23-EP, Hamburg: 2023-200889-BO-bet, Cologne: 23-1487 and Mainz: 2023-17399-§23b). The study protocol complies with the Declaration of Helsinki, the national medicine device regulation (MDR) laws and the international standards of good clinical practice (GCP). The study protocol (V.5, 24 November 2023) was designed following the Standard Protocol Items: Recommendations for Interventional Trials guidelines and is registered on https://drks.de/search/de/trial/DRKS00029129 . As study initiatior the University Medical Center Göttingen (UMG) is responsible for data ownership and data management of the VIRON study. The study data will be published within 6 months of the study being completed. After the publication of the primary results, all data are anonymised and published in an open-access journal to ensure access to the data for third parties. Trial registration number https://drks.de/search/de/trial/DRKS00029129 .German Research Foundation 50110000165
Care partner experience with telepresence robots in long-term care during COVID-19 pandemic
No full textObjective As people living with dementia move into long-term care (LTC), their care partners face a difficult role change from primary caregiver to visitor, losing a significant degree of control and direct care involvement. The COVID-19 pandemic exacerbated these challenges with health risks, changing care home protocols, and government policies. To help address these challenges, this study aimed to investigate the experiences of care partners who used telepresence robots to maintain contact with and care for their loved ones during the pandemic. Methods This study was guided by the Collaborative Action Research (CAR) approach. Along with interdisciplinary researchers and trainees, our team included patient and family partners as co-researchers throughout the project. We conducted semi-structured interviews with 20 care partners who used the robots in five urban Canadian LTC homes between May 2021 and August 2023. Results Thematic analysis identified four key themes characterizing their experiences using the robot: (a) decreases care partner burden, (b) facilitates care partner–staff relationship, (c) creates relational autonomy, and (d) expands the scope of what is possible. Conclusion The results of the study suggest that telepresence robots can play a useful role in enhancing the caregiving experience for informal care partners in multifaceted ways. Care partners reported positive benefits of having the robot assist their virtual visits. However, further research is needed to determine the sustainability of robot implementation among diverse geographic regions and care home compositions.Vancouver Foundation Participatory Action Researc
Shared prognostic information in amyotrophic lateral sclerosis – systematic assessment of the patients’ perception of neurofilament light chain and the ALS functional rating scale
No full textAbstract Background In amyotrophic lateral sclerosis (ALS), neurofilament light chain (NfL) was introduced as a prognostic biomarker. More recently, NfL values can be shared on the patient’s ALS app. Also, the ALS functional rating scale (ALSFRS-R) is an established patient-reported assessment of disease progression. The scale can be obtained during clinic visits or remotely. However, few systematic data are available on the patients’ perception of prognostic information about NfL and ALSFRS-R and the remote sharing of these data. Methods In a multicenter study, 149 ALS patients were assessed for their perception of shared information about NfL and ALSFRS-R using an investigator-designed survey and established questionnaires. The recommendation of NfL and ALSFRS-R to fellow patients was assessed using the Net Promoter Score (NPS). Burden by shared information was investigated in two distinct settings: (1) clinic information when receiving results on NfL and/or ALSFRS-R during clinic visits and (2) remote information about NfL values and self-rating of the ALSFRS-R via the ALS app. General anxiety was measured by the Fear of Progression Questionnaire – Short Form (FoP-Q-SF). Results Information about NfL and ALSFRS-R, respectively ( n = 149), were regarded as relevant for patients themselves (75.2% and 77.2%) and for research (98% and 96%). The NPS showed a high recommendation rate for NfL (+ 21) and ALSFRS-R (+ 26). Only a minority of patients perceived shared information about NfL as burdensome, with a lower burden in the clinic setting ( n = 1, 4.2%) than in the remote setting ( n = 8, 12%; p = 0.015). Remote digital assessment of the ALSFRS-R was well received, with a reported burden in 9.8% ( n = 9) of the participants. The FoP-Q-SF revealed fear of progression in 40% of the respondents ( n = 60). Conclusions This study underscored the relevance of information about NfL and ALSFRS-R from the patient’s perspective. Furthermore, patients proved to appreciate the relevance of this data for ALS research. Sharing information about NfL or ALSFRS-R was rarely perceived as burdensome even in a remote setting using the ALS app. These findings pave the way for further development of the patient-centered approach to sharing prognostic information in ALS