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Abstract The German initiative “National Research Data Infrastructure for Personal Health Data” (NFDI4Health) focuses on research data management in health research. It aims to foster and develop harmonized informatics standards for public health, epidemiological studies, and clinical trials, facilitating access to relevant data and metadata standards. This publication lists syntactic and semantic data standards of potential use for NFDI4Health and beyond, based on interdisciplinary meetings and workshops, mappings of study questionnaires and the NFDI4Health metadata schema, and literature search. Included are 7 syntactic, 32 semantic and 9 combined syntactic and semantic standards. In addition, 101 ISO Standards from ISO/TC 215 Health Informatics and ISO/TC 276 Biotechnology could be identified as being potentially relevant. The work emphasizes the utilization of standards for epidemiological and health research data ensuring interoperability as well as the compatibility to NFDI4Health, its use cases, and to (inter-)national efforts within these sectors. The goal is to foster collaborative and inter-sectoral work in health research and initiate a debate around the potential of using common standards.

BackgroundResources are increasingly spent on artificial intelligence (AI) solutions for medical applications aiming to improve diagnosis, treatment, and prevention of diseases. While the need for transparency and reduction of bias in data and algorithm development has been addressed in past studies, little is known about the knowledge and perception of bias among AI developers. ObjectiveThis study’s objective was to survey AI specialists in health care to investigate developers’ perceptions of bias in AI algorithms for health care applications and their awareness and use of preventative measures. MethodsA web-based survey was provided in both German and English language, comprising a maximum of 41 questions using branching logic within the REDCap web application. Only the results of participants with experience in the field of medical AI applications and complete questionnaires were included for analysis. Demographic data, technical expertise, and perceptions of fairness, as well as knowledge of biases in AI, were analyzed, and variations among gender, age, and work environment were assessed. ResultsA total of 151 AI specialists completed the web-based survey. The median age was 30 (IQR 26-39) years, and 67% (101/151) of respondents were male. One-third rated their AI development projects as fair (47/151, 31%) or moderately fair (51/151, 34%), 12% (18/151) reported their AI to be barely fair, and 1% (2/151) not fair at all. One participant identifying as diverse rated AI developments as barely fair, and among the 2 undefined gender participants, AI developments were rated as barely fair or moderately fair, respectively. Reasons for biases selected by respondents were lack of fair data (90/132, 68%), guidelines or recommendations (65/132, 49%), or knowledge (60/132, 45%). Half of the respondents worked with image data (83/151, 55%) from 1 center only (76/151, 50%), and 35% (53/151) worked with national data exclusively. ConclusionsThis study shows that the perception of biases in AI overall is moderately fair. Gender minorities did not once rate their AI development as fair or very fair. Therefore, further studies need to focus on minorities and women and their perceptions of AI. The results highlight the need to strengthen knowledge about bias in AI and provide guidelines on preventing biases in AI health care applications.

IntroductionAstrocytic Aquaporin 4 (AQP4) and Transient receptor potential vanilloid 4 (TRPV4) channels form a functional complex that likely influences cell volume regulation, the development of brain edema, and the severity of the ischemic injury. However, it remains to be fully elucidated whether blocking these channels can serve as a therapeutic approach to alleviate the consequences of having a stroke.Methods and resultsIn this study, we used in vivo magnetic resonance imaging (MRI) to quantify the extent of brain lesions one day (D1) and seven days (D7) after permanent middle cerebral artery occlusion (pMCAO) in AQP4 or TRPV4 knockouts and mice with simultaneous deletion of both channels. Our results showed that deletion of AQP4 or TRPV4 channels alone leads to a significant worsening of ischemic brain injury at both time points, whereas their simultaneous deletion results in a smaller brain lesion at D1 but equal tissue damage at D7 when compared with controls. Immunohistochemical analysis 7 days after pMCAO confirmed the MRI data, as the brain lesion was significantly greater in AQP4 or TRPV4 knockouts than in controls and double knockouts. For a closer inspection of the TRPV4 and AQP4 channel complex in the development of brain edema, we applied a real-time iontophoretic method in situ to determine ECS diffusion parameters, namely volume fraction (α) and tortuosity (λ). Changes in these parameters reflect alterations in cell volume, and tissue structure during exposure of acute brain slices to models of ischemic conditions in situ, such as oxygen-glucose deprivation (OGD), hypoosmotic stress, or hyperkalemia. The decrease in α was comparable in double knockouts and controls when exposed to hypoosmotic stress or hyperkalemia. However, during OGD, there was no decrease in α in the double knockouts as observed in the controls, which suggests less swelling of the cellular components of the brain.ConclusionAlthough simultaneous deletion of AQP4 and TRPV4 did not improve the overall outcome of ischemic brain injury, our data indicate that the interplay between AQP4 and TRPV4 channels plays a critical role during neuronal and non-neuronal swelling in the acute phase of ischemic injury.

BackgroundThe standard Fast Healthcare Interoperability Resources (FHIR) is widely used in health information technology. However, its use as a standard for health research is still less prevalent. To use existing data sources more efficiently for health research, data interoperability becomes increasingly important. FHIR provides solutions by offering resource domains such as “Public Health & Research” and “Evidence-Based Medicine” while using already established web technologies. Therefore, FHIR could help standardize data across different data sources and improve interoperability in health research. ObjectiveThe aim of our study was to provide a systematic review of existing literature and determine the current state of FHIR implementations in health research and possible future directions. MethodsWe searched the PubMed/MEDLINE, Embase, Web of Science, IEEE Xplore, and Cochrane Library databases for studies published from 2011 to 2022. Studies investigating the use of FHIR in health research were included. Articles published before 2011, abstracts, reviews, editorials, and expert opinions were excluded. We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and registered this study with PROSPERO (CRD42021235393). Data synthesis was done in tables and figures. ResultsWe identified a total of 998 studies, of which 49 studies were eligible for inclusion. Of the 49 studies, most (73%, n=36) covered the domain of clinical research, whereas the remaining studies focused on public health or epidemiology (6%, n=3) or did not specify their research domain (20%, n=10). Studies used FHIR for data capture (29%, n=14), standardization of data (41%, n=20), analysis (12%, n=6), recruitment (14%, n=7), and consent management (4%, n=2). Most (55%, 27/49) of the studies had a generic approach, and 55% (12/22) of the studies focusing on specific medical specialties (infectious disease, genomics, oncology, environmental health, imaging, and pulmonary hypertension) reported their solutions to be conferrable to other use cases. Most (63%, 31/49) of the studies reported using additional data models or terminologies: Systematized Nomenclature of Medicine Clinical Terms (29%, n=14), Logical Observation Identifiers Names and Codes (37%, n=18), International Classification of Diseases 10th Revision (18%, n=9), Observational Medical Outcomes Partnership common data model (12%, n=6), and others (43%, n=21). Only 4 (8%) studies used a FHIR resource from the domain “Public Health & Research.” Limitations using FHIR included the possible change in the content of FHIR resources, safety, legal matters, and the need for a FHIR server. ConclusionsOur review found that FHIR can be implemented in health research, and the areas of application are broad and generalizable in most use cases. The implementation of international terminologies was common, and other standards such as the Observational Medical Outcomes Partnership common data model could be used as a complement to FHIR. Limitations such as the change of FHIR content, lack of FHIR implementation, safety, and legal matters need to be addressed in future releases to expand the use of FHIR and, therefore, interoperability in health research.

In this study, the effect of media composition, N/P ratio and cultivation strategy on the formation of carotenoids in a Coelastrella sp. isolate was investigated. A two-stage process utilizing different media in the vegetative stage, with subsequent re-suspension in medium without nitrate, was employed to enhance the formation of carotenoids. The optimal growth and carotenoid content (β-carotene and lutein) in the vegetative phase were obtained by cultivation in M-8 and BG11 media. Use of a N/P ratio of 37.5 and low light intensity of 40 μmol m−2 s−1 (control conditions) led to optimal biomass production of up to 1.31 g L−1. Low concentrations of astaxanthin (maximum of 0.31 wt. %) were accumulated under stress conditions (nitrogen-deficient medium containing 1.5 % of NaCl and light intensity of 500 μmol m−2 s−1), while β-carotene and lutein (combined maximum of 2.12 wt. %) were produced under non-stress conditions. Lipid analysis revealed that palmitic (C16:0) and oleic (C18:1) constituted the main algal fatty acid chains (50.2 ± 2.1% of the total fatty acids), while esterifiable lipids constituted 17.2 ± 0.5% of the biomass by weight. These results suggest that Coelastrella sp. could also be a promising feedstock for biodiesel production.

Wetland bird species have been declining in population size worldwide as climate warming and land-use change affect their suitable habitats. We used species distribution models (SDMs) to predict changes in range dynamics for 64 non-passerine wetland birds breeding in Europe, including range size, position of centroid, and margins. We fitted the SDMs with data collected for the first European Breeding Bird Atlas and climate and land-use data to predict distributional changes over a century (the 1970s–2070s). The predicted annual changes were then compared to observed annual changes in range size and range centroid over a time period of 30 years using data from the second European Breeding Bird Atlas. Our models successfully predicted ca. 75% of the 64 bird species to contract their breeding range in the future, while the remaining species (mostly southerly breeding species) were predicted to expand their breeding ranges northward. The northern margins of southerly species and southern margins of northerly species, both, predicted to shift northward. Predicted changes in range size and shifts in range centroids were broadly positively associated with the observed changes, although some species deviated markedly from the predictions. The predicted average shift in core distributions was ca. 5 km yr ^−1 towards the north (5% northeast, 45% north, and 40% northwest), compared to a slower observed average shift of ca. 3.9 km yr ^−1 . Predicted changes in range centroids were generally larger than observed changes, which suggests that bird distribution changes may lag behind environmental changes leading to ‘climate debt’. We suggest that predictions of SDMs should be viewed as qualitative rather than quantitative outcomes, indicating that care should be taken concerning single species. Still, our results highlight the urgent need for management actions such as wetland creation and restoration to improve wetland birds’ resilience to the expected environmental changes in the future.

Background: The aim of this study was to analyze medication non-adherence by measuring serum drug levels (SDL) in patients presenting with acute decompensated heart failure (ADHF). Methods: Included in the study were chronic heart failure patients presenting with signs of acute decompensation. Blood sampling for the measurement of SDL was performed shortly after presentation. SDL were measured using liquid chromatography coupled with mass spectrometry. The estimation of SDL was calculated from the recommended chronic cardiac medications with the exception of drugs administered as part of the acute treatment prior to blood sampling. The patients were labeled as non-adherent when any one of the evaluated medications was not found in the serum. Results: Fifty patients with ADHF were prospectively enrolled. All of the evaluated drugs were detected in the sera of 28 (56%) patients. Non-adherence was diagnosed in the remaining 22 (44%) patients. None of the evaluated medications was detected in the sera of 5 (10%) patients. Conclusion: The estimation of SDL indicates that non-adherence to the recommended chronic therapy is a common problem among patients presenting with ADHF. This method should be an essential aspect of routine clinical evaluation in these patients.

Huntington's disease (HD) is an inherited neurodegenerative disorder with progressive impairment of motor, behavioral and cognitive functions. The clinical features of HD are closely related to the degeneration of the basal ganglia, predominantly the striatum. The main striatal output structure, the globus pallidus, strongly accumulates metalloprotein-bound iron, which was recently shown to influence the diffusion tensor scalar values. To test the hypothesis that this effect dominates in the iron-rich basal ganglia of HD patients, we examined the globus pallidus using DTI and T2 relaxometry sequences. Quantitative magnetic resonance (MR), clinical and genetic data (number of CAG repeats) were obtained from 14 HD patients. MR parameters such as the T2 relaxation rate (RR), fractional anisotropy (FA) and mean diffusivity (MD) were analysed. A positive correlation was found between RR and FA (R2=0.84), between CAG and RR (R2=0.59) and between CAG and FA (R2=0.44). A negative correlation was observed between RR and MD (R2=0.66). A trend towards correlation between CAG and MD was noted. No correlation between MR and clinical parameters was found. Our results indicate that especially magnetic resonance FA measurements in the globus pallidus of HD patients may be strongly affected by metalloprotein-bound iron accumulation.

Concern that European forest biodiversity is depleted and declining has provoked widespread efforts to improve management practices. To gauge the success of these actions, appropriate monitoring of forest ecosystems is paramount. Multi-species indicators are frequently used to assess the state of biodiversity and its response to implemented management, but generally applicable and objective methodologies for species' selection are lacking. Here we use a niche-based approach, underpinned by coarse quantification of species' resource use, to objectively select species for inclusion in a pan-European forest bird indicator. We identify both the minimum number of species required to deliver full resource coverage and the most sensitive species' combination, and explore the trade-off between two key characteristics, sensitivity and redundancy, associated with indicators comprising different numbers of species. We compare our indicator to an existing forest bird indicator selected on the basis of expert opinion and show it is more representative of the wider community. We also present alternative indicators for regional and forest type specific monitoring and show that species' choice can have a significant impact on the indicator and consequent projections about the state of the biodiversity it represents. Furthermore, by comparing indicator sets drawn from currently monitored species and the full forest bird community, we identify gaps in the coverage of the current monitoring scheme. We believe that adopting this niche-based framework for species' selection supports the objective development of multi-species indicators and that it has good potential to be extended to a range of habitats and taxa.

Aquaporin-4 (AQP4) is the primary cellular water channel in the brain and is abundantly expressed by astrocytes along the blood-brain barrier and brain-cerebrospinal fluid interfaces. Water transport via AQP4 contributes to the activity-dependent volume changes of the extracellular space (ECS), which affect extracellular solute concentrations and neuronal excitability. AQP4 is anchored by α-syntrophin (α-syn), the deletion of which leads to reduced AQP4 levels in perivascular and subpial membranes. We used the real-time iontophoretic method and/or diffusion-weighted magnetic resonance imaging to clarify the impact of α-syn deletion on astrocyte morphology and changes in extracellular diffusion associated with cell swelling in vitro and in vivo. In mice lacking α-syn, we found higher resting values of the apparent diffusion coefficient of water (ADCW) and the extracellular volume fraction (α). No significant differences in tortuosity (λ) or non-specific uptake (k'), were found between α-syn-negative (α-syn -/-) and α-syn-positive (α-syn +/+) mice. The deletion of α-syn resulted in a significantly smaller relative decrease in α observed during elevated K(+) (10 mM) and severe hypotonic stress (-100 mOsmol/l), but not during mild hypotonic stress (-50 mOsmol/l). After the induction of terminal ischemia/anoxia, the final values of ADCW as well as of the ECS volume fraction α indicate milder cell swelling in α-syn -/- in comparison with α-syn +/+ mice. Shortly after terminal ischemia/anoxia induction, the onset of a steep rise in the extracellular potassium concentration and an increase in λ was faster in α-syn -/- mice, but the final values did not differ between α-syn -/- and α-syn +/+ mice. This study reveals that water transport through AQP4 channels enhances and accelerates astrocyte swelling. The substantially altered ECS diffusion parameters will likely affect the movement of neuroactive substances and/or trophic factors, which in turn may modulate the extent of tissue damage and/or drug distribution.

To determine the association between unfractionated heparin (UFH) dose and the rate of postoperative bleeding and thrombosis events in pediatric cardiac patients. We tested the hypothesis that high-dose UFH is associated with higher rates of bleeding and thrombosis. This is a retrospective review of pediatric patients admitted to the cardiac intensive care unit following cardiac surgery between November 2016 and December 2017. Peripheral venous thrombosis was excluded from analysis. Bleeding was defined as spontaneous bleeding remote from procedural manipulation. Postoperative UFH dosing strategy was categorized into 3 groups: no UFH, low-dose UFH (<15 U/kg/h) and high-dose UFH (≥15 U/kg/h). Statistical analysis was performed using multivariable logistic regression. We observed 966 consecutive patients (median age, 1.37 years; interquartile range, 0.27-5.50 years) during their stay in the cardiac intensive care unit. There were 94 patients (10%) with bleeding and 52 patients (5%) with thrombosis during follow-up. Patients receiving high-dose UFH experienced significantly more bleeding (odds ratio, 2.35; 95% confidence interval, 1.45-3.95) and thrombosis events (odds ratio, 3.65; 95% confidence interval, 1.81-7.38) compared with patients receiving low-dose UFH. The odds of bleeding (odds ratio, 0.81; 95% confidence interval, 0.45-1.47) and thrombosis (odds ratio, 0.59; 95% confidence interval, 0.26-1.35) were similar in the low-dose UFH and no-UFH groups. Bleeding remote from immediate postsurgical bleeding occurs uncommonly in pediatric patients following cardiac surgery. Anticoagulation with high-dose UFH is associated with higher bleeding rates as well as higher thrombosis rates. Indications for high-dose UFH should be carefully considered to reduce the rate of bleeding in this population. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to analyze medication non-adherence by measuring serum drug levels (SDL) in patients presenting with acute decompensated heart failure (ADHF). Methods. Included in the study were chronic heart failure patients presenting with signs of acute decompensation. Blood sampling for the measurement of SDL was performed shortly after presentation. SDL were measured using liquid chromatography coupled with mass spectrometry. The estimation of SDL was calculated from the recommended chronic cardiac medications with the exception of drugs administered as part of the acute treatment prior to blood sampling. The patients were labeled as non-adherent when any one of the evaluated medications was not found in the serum. Results. Fifty patients with ADHF were prospectively enrolled. All of the evaluated drugs were detected in the sera of 28 (56%) patients. Non-adherence was diagnosed in the remaining 22 (44%) patients. None of the evaluated medications was detected in the sera of 5 (10%) patients. Conclusion. The estimation of SDL indicates that non-adherence to the recommended chronic therapy is a common problem among patients presenting with ADHF. This method should be an essential aspect of routine clinical evaluation in these patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Coffee irritates the gastric mucosa disrupting its barrier and increasing the risk of peptic ulcers. However, caffeine's contribution to these effects has not yet been elucidated. In this study we looked at the local effect of caffeine on the microcirculation and nitric oxide production in rats together with systemic marker of oxidative stress malondialdehyde as possible mechanisms whereby caffeine might participate in mucosal barrier impairment. Materials and Methods: Four groups of rats were anesthetized and administered as a bolus four diff erent intraperitoneal doses of caffeine (0, 1, 10 and 50 mg kg-1 b.wt.). The gastric submucosal microcirculation and nitric oxide production were then recorded for 2.5 hours by in situ microdialysis using the flow marker ethanol. At the completion of the experiments, plasma caffeine and malondialdehyde levels as well as morphological mucosal injury were determined. Results: There were no major differences in the macro- or microscopic pictures of the mucosa among the groups. Local microcirculatory (ethanol out/in ratio) and nitric oxide monitoring failed to demonstrate statistically significant changes as did measurement of plasma malondialdehyde in response to caffeine injections. Conclusions: Caffeine perse seems unlikely to contribute to the gastric mucosal barrier injury associated with coffee consumption by alterations in nutritive blood flow, nitric oxide production or aggravation of systemic oxidative stress. This information is relevant for better understanding of the mechanisms involved in caffeine-mediated influences on gastric physiology in relation to the irritant effects of coffee. [ABSTRACT FROM AUTHOR]

An abstract of the medical research "ANALYTICAL SUPPORT OF HYPERTENSION TREATMENT. DIURETICS," by Vilma Habrdova, Viktor Vorisek, Jiri Ceral, Karel Macek, Zuzana Svetlikova, Pavel Zivny and Vladimir Palicka is presented.