University of Copenhagen

Salloch and Eriksen (2024) present a compelling case for including patients as co-reasoners in medical decision-making involving artificial intelligence (AI). Drawing on O'Neill's neo- Kantian framework (1989), they argue that the "human in the loop" concept should extend beyond physicians to encompass patients as active participants in the reasoning process. While we commend this perspective, we suggest it can be extended further: certain types of medical AI, particularly large language models (LLMs), should also be considered as potential co-reasoners.

Introduction Type 1 diabetes mellitus (T1DM) is a disorder that arises following the selective autoimmune destruction of the insulin-producing beta cells. Beta-cell protective or beta-cell regenerative approaches have gained wider attention, and pharmacological approaches to protect the patient’s own insulin-producing beta-cell mass have been proposed. Verapamil is an L-type calcium channel blocker that has been reported to effectively lowers beta-cell thioredoxin-interacting protein expression in rodent beta cells and islets, as well as in human islets, and thus promotes functional beta-cell mass. Methods and analysis The trial is a multicentre, randomised, double-blind, placebo-controlled trial in participants with T1DM, investigating the effect of verapamil on preservation of beta-cell function (Ver-A-T1D). A total of 120 participants will be randomised in a 2:1 ratio between 360 mg verapamil and placebo, administered orally once daily. T1DM patients aged ≥18 and <45 years will be eligible for recruitment within 6 weeks of diagnosis (defined as day of starting insulin therapy). The primary objective will be to determine the changes in stimulated C-peptide response during the first 2 hours of a mixed meal tolerance test at baseline and after 12 months for 360 mg verapamil administered orally once daily versus placebo. Secondary objectives include the effects of 360 mg verapamil on (1) fasting C-peptide, (2) dried blood spot C-peptide, (3) glycated haemoglobin, (4) daily total insulin dose, (5) time in range by intermittent continuous glucose monitoring measures, (6) other biomarkers related to immunological changes and beta-cell death and (6) safety (vital signs, ECG). Ethics and dissemination Ethics approval was sought from the research ethics committee of all participating countries. All participants provided written informed consent before joining the study. Ver-A-T1D received first regulatory and ethical approvals in Austria. The publication policy is set in the innovative approach towards understanding and arresting type 1 diabetes grant agreement ( www.innodia.eu ). Trial registration number EudraCT, 2020-000435-45; ClinicalTrials.gov, NCT04545151 . Protocol version: Version 8.0 (08 November 2021).

In this study, the mechanism of selfpromoted N‐glycosylations is extensively investigated through kinetic experiments, computational studies, and nucleophilic competition experiments. Based on the findings, the mechanism is proposed to be initiated by proton transfer from the acidic sulfonyl carbamate to the trichloroacetimidate, upon formation of an associated contact ion pair. This ion pair then collapses in an SN1‐like fashion, with formation of an oxocarbeniumion‐like intermediate. According to the proposed mechanism, stereospecificity arises from the associated nature of all intermediates formed throughout the reaction. During the mechanistic study, it was also found that the sulfonyl carbamates have catalytic properties if a competing nucleophile is present.

The active site Cys residue in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is sensitive to oxidation by hydrogen peroxide (H2O2), with this resulting in enzyme inactivation. This re-routes the carbon flux from glycolysis to the pentose phosphate pathway favoring the formation of NADPH and synthetic intermediates required for antioxidant defense and repair systems. Consequently, GAPDH inactivation serves as a redox switch for metabolic adaptation under conditions of oxidative stress. However, there is a major knowledge gap as to how GAPDH is efficiently oxidized and inactivated, when the increase in intracellular H2O2 is modest, and there is a high concentration of alternative (non-signaling) thiols and efficient peroxide removing systems. We have therefore explored whether GAPDH inactivation is enhanced by two factors of in vivo relevance: macromolecular crowding, an inherent property of biological environments, and the presence of bicarbonate, an abundant biological buffer. Bicarbonate is already known to modulate H2O2 metabolism via formation of peroxymonocarbonate. GAPDH activity was assessed in experiments with low doses of H2O2 under both dilute and crowded conditions (induced by inert high molecular mass polymers and small molecules), in both the absence and presence of 25 mM sodium bicarbonate. H2O2-induced inactivation of GAPDH was observed to be significantly enhanced under macromolecular crowding conditions, with bicarbonate having an additional effect. These data strongly suggest that these two factors are of major importance in redox switch mechanisms involving GAPDH (and possibly other thiol-dependent systems) within the cellular environment.

Organometallics can be used as precursors for electrophilic ²¹¹At‐statinations. In this report, we compared the potential of aryl trimethylsilanes, ‐germanes, or –stannanes to be used as precursors to ²¹¹At‐label highly reactive tetrazines. Tetrazines can be used for pretargeted radioligand therapies or be applied as synthons to radiolabel rapidly and orthogonally a broad set of precursors such as peptides, mAbs or nanomedicines. All precursors could successfully be synthesized and radiolabeled. The reactivity of organogermanium reagents ranged between those of respective organotin and organosilicon precursors. Moreover, organogermanium reagents proved promising for accessing more complex and polar tetrazine scaffolds. In contrast to organotin derivatives, the use of protecting groups could be avoided for organogermanium and ‐silicon precursors. The developed ²¹¹At‐labeled tetrazines could be labeled in radiochemical conversions of 60–90 %. Organogermanium and ‐silicon precursors were clearly advantaged as additional deprotection steps could avoided. Reported labeling procedures allow astatinations of highly reactive tetrazines to be used for pretargeted approaches or to applied as highly reactive synthons to label the next‐generation of ²¹¹At‐labeled radiopharmaceuticals.

This study delves into the intricate interactions between surface‐near species, OH and H2O, on electrodes in electrochemical interfaces. These species are an inevitable part of many electrocatalytic energy conversion reactions such as the oxygen reduction reaction. In our modeling, we utilize high statistics on a dataset of complex solid solutions with high atomic variability to show the emergence of H2O‐metal covalent bonds under specific conditions. Based on density functional theory (DFT) calculations of adsorption energies on many thousands of different surface compositions, we provide a quantifiable physical understanding of this induced water covalency, which is rooted in simple quantum mechanics. Directional hydrogen bonding between surface‐near H2O and OH, enables surface bonding electrons to delocalize, mediated by near‐symmetrical adsorbate resonance structures. The different adsorbate resonance structures differ by surface coordination explaining the induced H2O‐metal bonding.

During the French Revolution, thousands of revolutionaries and royalists fled the turmoil in French islands. Many went to nearby islands, from which they could observe events. Situated between Martinique and Guadeloupe, Dominica had a majority French population and a long history of connection with its French neighbors. This article uses the case of Dominica to explore the effects of the French Revolution on a non-French island in the Eastern Caribbean. From the start, its proximity to the French islands led to its entanglement in revolutionary politics. It was the first British island to receive refugees, and the influx of people of all racial, social, and political backgrounds into Dominica posed challenges for island officials. Officials had to determine on what terms to admit emigrants, whether they posed a threat to the colony, and how to feed and house them. They also worried about the influences of foreigners and revolutionary ideas on their own disaffected free and enslaved populations. This article argues that Dominica's location, heterogeneous population, and internal instability allowed it to become a node for regional migration and information networks that embroiled it in the turmoil that engulfed its neighbors and ultimately threatened British control of the island.

This article attempts to explain the peculiar role of Isaac Newton in the poetry of Friedrich Schiller. I show that Newtonian ideas appear from the earliest poems in Anthologie auf das Jahr 1782 wherein gravity is used mainly as a metaphor for love. Newton is made a culprit, in Schiller's cosmological poems, for the destruction of the spheres and for the poet's despair in the ‘empty’, Newtonian universe. I chart the changing role of Newton in the later poetry of Schiller, where it is mainly his Opticks that interests the poet, who at this point has a thoroughly negative idea of the scientist, probably inspired by Goethe. Newton's famous experiment with the prism is figured as being the opposite of the poetry with which Schiller sought to unify (rather than refract) nature.

Iron deficiency is the main cause of anaemia, especially in premenopausal due to heavy menstrual bleeding. In this case report, an asymptomatic woman presented with a haemoglobin level of 3.9 mmol/l. Due to uterine fibroids, she was scheduled for myomectomy, and she was treated with IV iron. Fourteen days post infusion her haemoglobin level was 6.3 mmol/l. This highlights the importance of screening women for heavy menstrual bleeding causing iron deficiency, and encourage at-risk women to take iron supplements. Furthermore, one should be aware of IV iron therapy as an alternative to blood transfusion in treating iron deficiency anaemia.

Circularly polarized luminescence (CPL) from chiral molecules is attracting much attention due to its potential use in optical materials. However, formulation of CPL emitters as molecular solids typically deteriorates photophysical properties in the aggregated state leading to quenching and unpredictable changes in CPL behavior impeding materials development. To circumvent these shortcomings, a supramolecular approach can be used to isolate cationic dyes in a lattice of cyanostar‐anion complexes that suppress aggregation‐caused quenching and which we hypothesize can preserve the synthetically‐crafted chiroptical properties. Herein, we verify that supramolecular assembly of small‐molecule ionic isolation lattices (SMILES) allows translation of molecular ECD and CPL properties to solids. A series of cationic helicenes that display increasing chiroptical response is investigated. Crystal structures of three different packing motifs all show spatial isolation of dyes by the anion complexes. We observe the photophysical and chiroptical properties of all helicenes are seamlessly translated to water soluble nanoparticles by the SMILES method. Also, a DMQA helicene is used as FRET acceptor in SMILES nanoparticles of intensely absorbing rhodamine antennae to generate an 18‐fold boost in CPL brightness. These features offer promise for reliably accessing bright materials with programmable CPL properties.

This contribution is an introduction to the thematic collection ‘Digitally enabled geoscience workflows: Unlocking the power of our data’. The goal of the collection is to show how advances in data-science are transforming the process of scientific research and fueling a new generation of energy geoscience workflows. These workflows are providing game-changing advances in terms of time saving on complex tasks, improved consistency and repeatability of interpretation, and utilization of scarce experienced geoscientists. Eight articles have been accepted for publication as part of this thematic collection, five in Petroleum Geoscience and three in Geoenergy . We provide a short summary of each of these contributions and hope that this collection will provide inspiration and examples of the breadth of workflows that can be transformed by embracing the coming wave of digital technologies. This thematic collection resulted from an open call for papers on the theme of ‘Digitally enabled geoscience workflows: Unlocking the power of our data’. Eight contributions have been accepted for publication, five in Petroleum Geoscience and three in Geoenergy . Although the energy geoscience industry typically employs statistical workflows that are highly data intensive, it has been relatively slow to adopt modern data-science technologies. This is a result of historical reliance on established methods, the cost and complexity of adopting new technologies, and cultural and organizational challenges. However, with improved computing power and growing interest in data sciences, this is now changing rapidly, with the development and application of data-driven workflows an active area of research in energy geoscience. It is expected that the publication of research contributions in this area will continue to accelerate, with this collection providing a useful summary of the current key emerging themes.

Chemical modification of proteins is of growing importance to generate new molecular probes for chemical biology and for the development of new biopharmaceuticals. For example, two approved, long‐acting insulin variants are lipidated at the LysB29 side‐chain. Acylations of proteins have so far been performed in batch‐mode. Here we describe the use of flow chemistry for site‐selective acylation of a small protein, insulin. To the best of our knowledge this is the first report on flow chemistry for chemical modification of insulin. The first step was to develop reaction conditions for acylation of Lys B29 that gave a soluble mixture and thus was compatible with flow chemistry in a microreactor; this included selection of a soluble base. Secondly, the conditions, such as reagent ratios and flow rate were optimized. Third, the use of these conditions for the acylation with a wide range of acids was demonstrated. Finally, Boc‐protected insulins were synthesized. Insulin remained stable towards these flow chemistry conditions. This use of flow chemistry for the chemical modification of insulin opens the prospect of producing chemically modified biopharmaceuticals by flow chemistry with fewer byproducts.

The synthesis of diradical organic compounds has garnered significant attention due to their thermally accessible spin inversion and optoelectronic properties. Yet, preparing such stable structures with high open‐shell behavior remains challenging. Herein, we report the synthesis and properties of four π‐extended, fused fluorene derivatives with high diradical character, taking advantage of a molecular design where the closed‐shell does not include any Clar sextet, comparatively to a maximum of 5 in the corresponding open‐shell state. This led to an unusual open‐shell triplet ground state with an outstanding singlet‐triplet energy difference (ΔEST) of ca. 19 kcal/mol, one of the highest values reported to date for an all‐carbon conjugated scaffold. Incorporation of dithiafulvene units at each end of the molecule (at the five‐membered rings) furnishes extended tetrathiafulvalenes (TTFs) undergoing reversible oxidations to the radical cation and diradical dication. The various pro‐aromatic structures presented herein show highly localized spin density and a limited conjugation due to the confined π‐electrons in the aromatic cycles, as supported by ¹H NMR, UV/Visible, EPR spectroscopy and DFT calculations.

Electrochemical oxidation-reduction processes in the presence of anions have been widely explored for surface preparation of tailor-made copper catalysts. Nevertheless, the role of the anion and which sites geometries induce remains elusive. To address this uncertainty, we have assessed the effect of chloride on the surface modification of a well-defined Cu(111) single crystalline electrode using a potential-pulse technique. The morphology analysis revealed the formation of shape hexagonal microstructures homogeneously distributed on the single-facet surface. This shape was nearly similar to a (310) particle growing along the direction of the (111) orientation. Herein, we provide experimental insights supporting the idea that chloride induces the formation of n(100)x(110) domains, whereas the crystal-substrate orientation determines the growth direction of the new crystallographic phase. The present work offers a straightforward approach that enables precise control over the modification of highly ordered surfaces. This strategy is relevant for rationally assessing anion effects on the formation of distinct site geometries.

Up to 70% of all sudden cardiac deaths (SCD) in persons under 50 years are due to inherited cardiovascular diseases. First-degree relatives to younger SCD patients should be evaluated for inherited cardiovascular disease, as argued in this review. An improved understanding of SCD subtypes and genetics is expected to improve risk stratification and SCD prevention. Preventing ischaemic heart disease (IHD) is a cornerstone as IHD is the most common cause of SCD.

Cardiac arrest (CA) survivorship is associated with risk of cognitive deficits, emotional and social consequences. Early recognition of these symptoms and referral to rehabilitation is considered to be the fifth link in the chain of survival. This review highlights the need for a national standardized care plan for CA survivors based on a multidisciplinary approach. A patient-tailored law-bound rehabilitation form is essential to proper services in Denmark and should be mandatory. Further research within different rehabilitation areas following CA is warranted to support clinical practice.