The application of data altruism in clinical research through empirical and legal analysis lenses

BackgroundThe legal framework for clinical research in the EU is complex and the lack of harmonization of the relevant legal and ethical rules remains one of the main challenges for stakeholders in the field. The recently adopted Data Governance Act (DGA) and the proposal for a European Health Data Space (EHDS) promise to solve the existing challenges with respect to access to and (re)use of personal data for research, but also risk to further complexify the field. The DGA introduced a novel mechanism – data altruism. Data altruism is understood as the voluntary sharing of personal and non-personal data, based on the consent of data subjects or the permission of natural and legal persons, without seeking a reward and for objectives of general interest. This study aimed to gain insights into the opinion of clinical research stakeholders on data altruism, and to critically discuss key issues pertaining to the application of data altruism from a legal point of view.MethodsSemi-structured interviews with (1) data protection officers (DPOs) and legal experts working with commercial and academic sponsors of clinical trials, (2) investigators, and (3) members of research ethics committees. Data underwent framework analysis. The legal discussion was comprised of legal doctrinal research with focus on the DGA, EHDS proposal, and the interplay with the EU General Data Protection Regulation (GDPR).ResultsFourteen experts took part in the interviews, more than half of which were DPOs/legal experts. Interviewees were based in seven EU Member states and the United Kingdom. The majority of participants were critical towards the data altruism mechanism and pointed out challenges and risks associated with its application.ConclusionAlthough data altruism holds the potential to facilitate data sharing, its application in clinical research at the moment is still riddled with uncertainties. The interplay of the DGA rules with the provisions of the GDPR and the EHDS proposal are insufficiently clear and further efforts from the legislator are required to build a working, patient-centered, and research fostering data altruism system

Comparative solution and structural studies of half-sandwich rhodium and ruthenium complexes bearing curcumin and acetylacetone

Half-sandwich organometallic complexes of curcumin are extensively investigated as anticancer compounds.Speciation studies were performed to explore the solution stability of curcumin complexes formed with [Rh(η5- C5Me5)(H2O)3]2+. Acetylacetone (Hacac), as the simplest β-diketone ligand bearing (O,O) donor set, was involved for comparison and its Ru(η6‑p‑cymene), Ru(η6‑toluene) complexes were also studied. 1H NMR, UV–visible and pH-potentiometric titrations revealed a clear trend of stability constants of the acac complexes: Ru(η6‑p‑cymene) > Ru(η6‑toluene) > Rh(η5-C5Me5). Despite this order, the highest extent of complex formation is seen for the Rh(η5-C5Me5) complexes at pH 7.4. Formation constant of [Rh(η5-C5Me5)(H2curcumin) (H2O)]+ reveals similar solution stability to that of the acac complex. Additionally, structures of two complexes were determined by X-ray crystallography. The in vitro cytotoxicity of curcumin was not improved by the complexation with these organometallic cations.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/2875]This is the peer-reviewed version of the following article: Meszaros, J. P.; Poljarević, J.; Gal, T. G.; May, N. V.; Spengler, G.; Enyedy, E. A. Comparative Solution and Structural Studies of Half-Sandwich Rhodium and Ruthenium Complexes Bearing Curcumin and Acetylacetone. Journal of Inorganic Biochemistry 2019, 195, 91–100. [https://doi.org/10.1016/j.jinorgbio.2019.02.015

Supplementary data for the article: Meszaros, J. P.; Poljarević, J.; Gal, T. G.; May, N. V.; Spengler, G.; Enyedy, E. A. Comparative Solution and Structural Studies of Half-Sandwich Rhodium and Ruthenium Complexes Bearing Curcumin and Acetylacetone. Journal of Inorganic Biochemistry 2019, 195, 91–100. https://doi.org/10.1016/j.jinorgbio.2019.02.015

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2019.02.015]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2873

Supplementary data for the article: Meszaros, J. P.; Poljarević, J.; Gal, T. G.; May, N. V.; Spengler, G.; Enyedy, E. A. Comparative Solution and Structural Studies of Half-Sandwich Rhodium and Ruthenium Complexes Bearing Curcumin and Acetylacetone. Journal of Inorganic Biochemistry 2019, 195, 91–100. https://doi.org/10.1016/j.jinorgbio.2019.02.015

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2019.02.015]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2873

An Integrative Information Aqueduct to Close the Gaps between Satellite Observation of Water Cycle and Local Sustainable Management of Water Resources

[EN] The past decades have seen rapid advancements in space-based monitoring of essential water cycle variables, providing products related to precipitation, evapotranspiration, and soil moisture, often at tens of kilometer scales. Whilst these data effectively characterize water cycle variability at regional to global scales, they are less suitable for sustainable management of local water resources, which needs detailed information to represent the spatial heterogeneity of soil and vegetation. The following questions are critical to effectively exploit information from remotely sensed and in situ Earth observations (EOs): How to downscale the global water cycle products to the local scale using multiple sources and scales of EO data? How to explore and apply the downscaled information at the management level for a better understanding of soil-water-vegetation-energy processes? How can such fine-scale information be used to improve the management of soil and water resources? An integrative information flow (i.e., iAqueduct theoretical framework) is developed to close the gaps between satellite water cycle products and local information necessary for sustainable management of water resources. The integrated iAqueduct framework aims to address the abovementioned scientific questions by combining medium-resolution (10 m-1 km) Copernicus satellite data with high-resolution (cm) unmanned aerial system (UAS) data, in situ observations, analytical- and physical-based models, as well as big-data analytics with machine learning algorithms. This paper provides a general overview of the iAqueduct theoretical framework and introduces some preliminary results.The authors would like to thank the European Commission and Netherlands Organisation for Scientific Research (NWO) for funding, in the frame of the collaborative international consortium (iAqueduct) financed under the 2018 Joint call of the Water Works 2017 ERA-NET Cofund. This ERA-NET is an integral part of the activities developed by the Water JPI (Project number: ENWWW.2018.5); the EC and the Swedish Research Council for Sustainable Development (FORMAS, under grant 2018-02787); Contributions of B. Szabo was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (grant no. BO/00088/18/4).Su, Z.; Zeng, Y.; Romano, N.; Manfreda, S.; Francés, F.; Ben Dor, E.; Szabó, B.... (2020). An Integrative Information Aqueduct to Close the Gaps between Satellite Observation of Water Cycle and Local Sustainable Management of Water Resources. Water. 12(5):1-36. https://doi.org/10.3390/w12051495S13612

Gαi2- and Gαi3-Specific Regulation of Voltage-Dependent L-Type Calcium Channels in Cardiomyocytes

BACKGROUND: Two pertussis toxin sensitive G(i) proteins, G(i2) and G(i3), are expressed in cardiomyocytes and upregulated in heart failure. It has been proposed that the highly homologous G(i) isoforms are functionally distinct. To test for isoform-specific functions of G(i) proteins, we examined their role in the regulation of cardiac L-type voltage-dependent calcium channels (L-VDCC). METHODS: Ventricular tissues and isolated myocytes were obtained from mice with targeted deletion of either Gα(i2) (Gα(i2) (-/-)) or Gα(i3) (Gα(i3) (-/-)). mRNA levels of Gα(i/o) isoforms and L-VDCC subunits were quantified by real-time PCR. Gα(i) and Ca(v)α(1) protein levels as well as protein kinase B/Akt and extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation levels were assessed by immunoblot analysis. L-VDCC function was assessed by whole-cell and single-channel current recordings. RESULTS: In cardiac tissue from Gα(i2) (-/-) mice, Gα(i3) mRNA and protein expression was upregulated to 187 ± 21% and 567 ± 59%, respectively. In Gα(i3) (-/-) mouse hearts, Gα(i2) mRNA (127 ± 5%) and protein (131 ± 10%) levels were slightly enhanced. Interestingly, L-VDCC current density in cardiomyocytes from Gα(i2) (-/-) mice was lowered (-7.9 ± 0.6 pA/pF, n = 11, p<0.05) compared to wild-type cells (-10.7 ± 0.5 pA/pF, n = 22), whereas it was increased in myocytes from Gα(i3) (-/-) mice (-14.3 ± 0.8 pA/pF, n = 14, p<0.05). Steady-state inactivation was shifted to negative potentials, and recovery kinetics slowed in the absence of Gα(i2) (but not of Gα(i3)) and following treatment with pertussis toxin in Gα(i3) (-/-). The pore forming Ca(v)α(1) protein level was unchanged in all mouse models analyzed, similar to mRNA levels of Ca(v)α(1) and Ca(v)β(2) subunits. Interestingly, at the cellular signalling level, phosphorylation assays revealed abolished carbachol-triggered activation of ERK1/2 in mice lacking Gα(i2). CONCLUSION: Our data provide novel evidence for an isoform-specific modulation of L-VDCC by Gα(i) proteins. In particular, loss of Gα(i2) is reflected by alterations in channel kinetics and likely involves an impairment of the ERK1/2 signalling pathway

The peak-flux of GRB 221009A measured with GRBAlpha

The brightest gamma-ray burst ever observed, long-duration GRB 221009A, was detected by GRBAlpha nano-satellite without saturation. We present light curves of the prompt emission in 13 energy bands, from 80 keV to 950 keV, and perform a spectral analysis to calculate the peak flux and peak isotropic-equivalent luminosity. Since the satellite's attitude information is not available for the time of this GRB, more than 200 incident directions were probed in order to find the median luminosity and its systematic uncertainty. We found that the peak flux in the $80-800$ keV range (observer frame) was $F_{\rm{ph}}^{\rm{p}}=1300_{-200}^{+1200}$ ph cm$^{-2}$s$^{-1}$ or $F_{\rm{erg}}^{\rm{p}}=5.7_{-0.7}^{+3.7}\times10^{-4}$ erg cm$^{-2}$s$^{-1}$ and the fluence in the same energy range of the first GRB episode lasting 300 s, which was observable by GRBAlpha, was $S=2.2_{-0.3}^{+1.4}\times10^{-2}$ erg cm$^{-2}$ or $S^{\rm{bol}}=4.9_{-0.5}^{+0.8}\times10^{-2}$ erg cm$^{-2}$ for the extrapolated range of $0.9-8,690$ keV. We infer the isotropic-equivalent released energy of the first GRB episode to be $E_{\rm{iso}}^{\rm{bol}}=2.8_{-0.5}^{+0.8}\times10^{54}$ erg in the $1-10,000$ keV band (rest frame at $z=0.15$). The peak isotropic-equivalent luminosity in the $92-920$ keV range (rest frame) was $L_{\rm{iso}}^{\rm{p}}=3.7_{-0.5}^{+2.5}\times10^{52}$ erg s$^{-1}$ and the bolometric peak isotropic-equivalent luminosity was $L_{\rm{iso}}^{\rm{p,bol}}=8.4_{-1.5}^{+2.5}\times10^{52}$ erg s$^{-1}$ (4 s scale) in the $1-10,000$ keV range (rest frame). The peak emitted energy is $E_p^\ast=E_p(1+z)=1120\pm470$ keV. Our measurement of $L_{\rm{iso}}^{\rm{p,bol}}$ is consistent with the Yonetoku relation. It is possible that, due to the spectral evolution of this GRB and orientation of GRBAlpha at the peak time, the true values of peak flux, fluence, $L_{\rm{iso}}$, and $E_{\rm{iso}}$ are even higher. [abridged]Comment: 7 pages, 7 figures, 1 table, accepted for publication in Astronomy & Astrophysic