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Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: M. Eltokhy, U. Barth, F. Meyer, D. Langer und Z. Halloul geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. Für Bildmaterial oder anderweitige Angaben innerhalb des Manuskripts, über die Patient/-innen zu identifizieren sind, liegt von ihnen und/oder ihren gesetzlichen Vertretern/Vertreterinnen eine schriftliche Einwilligung vor.

Structural maintenance of chromosomes (SMC) are ubiquitously distributed proteins involved in chromosome organization. Deletion of smc causes severe growth phenotypes in many organisms. Surprisingly, smc can be deleted in Corynebacterium glutamicum , a member of the Actinomycetota phylum, without any apparent growth phenotype. SMC in C. glutamicum is loaded in a ParB-dependent fashion to the chromosome and functions in replichore cohesion. The unexpected absence of a growth phenotype in the smc mutant prompted us to screen for synthetic interactions within C. glutamicum . We generated a high-density Tn5 library from wild-type and smc -deleted C. glutamicum strains. Transposon sequencing data revealed that the DNA translocase FtsK is essential in an smc -deletion strain. In wild-type cells, FtsK localized to the septa and cell poles, showing polar enrichment during the earlier stages of the life cycle and relocating to the septum in the later stages. However, deletion of smc resulted in an earlier onset of pole-to-septum FtsK relocation, suggesting that prolonged FtsK complex activity is both required and sufficient to compensate for the absence of SMC, thus achieving efficient chromosome segregation in C. glutamicum . Deletion of ParB increases SMC and FtsK mobility. While the change in SMC dynamics aligns with previous data showing ParB's role in SMC loading on DNA, the change in FtsK mobility suggests defects in chromosome segregation. Based on our data, we propose an efficient mechanism for reliable DNA segregation in the absence of replichore arm cohesion in smc mutant cells.IMPORTANCEFaithful DNA segregation is of fundamental importance for life. Bacteria have developed efficient systems to coordinate chromosome compaction, DNA segregation, and cell division. A key factor in DNA compaction is the SMC complex that is found to be essential in many bacteria. In members of the Actinomycetota, smc is dispensable, but the reason for the lack of an smc phenotype in these bacteria remained unclear. We show here that the divisome-associated DNA pump FtsK can compensate for SMC loss and the subsequent loss in correct chromosome organization. In cells with distorted chromosomes, FtsK is recruited and stabilized earlier to the septum, allowing for DNA segregation for a larger part of the cell cycle, until chromosomes are segregated.

Alkyl nickel intermediates relevant to catalytic processes often feature agostic stabilization, but relatively little is known about the situation in oligonickel systems. The dinickel(I) complex K[LNi I 2 ], which is based on a compartmental pyrazolato-bridged ligand L 3- with two β-diketiminato chelate arms, or its masked version, the dihydride complex [KL(Ni II -H) 2 ] that readily releases H 2 , oxidatively add methyl tosylate to give diamagnetic [LNi II 2 (CH 3 )] ( 1 ) with d (Ni···Ni) ≈ 3.7 Å. Structural characterization shows that the methyl group in 1 is bound to one Ni II and exhibits an intramolecular agostic interaction with the more distant Ni II . This is supported spectroscopically (viz., a ν(C-H) stretch at 2658 cm -1 and lowered 1 J C-H of 114 Hz) and by DFT calculations, including topological analysis of the computed electron density for 1 . NMR spectroscopy reveals very fast hopping of the CH 3 group between the two Ni II ions, which according to DFT has a minute barrier of 4 kcal mol -1 and proceeds via a planar CH 3 moiety in the transition state (Walden-like inversion). The alkylidene group in K[LNi 2 (μ-CHSi(Me 3 ) 3 )], obtained from the reaction of [KL(Ni-H) 2 ] with N 2 CHSiMe 3 , is symmetrically bridging. This work provides new insight into the stabilization and dynamics of alkyl ligands at dinickel sites with a constrained metal···metal distance.

Background: This study aimed to investigate whether changes in capillary refill (CR) time precede macrovascular signs of deterioration in a human model of blood loss shock. The study was conducted at the Department of Emergency Medicine in Linköping, Sweden, and involved 42 healthy volunteers aged 18-45. Participants were randomized into two provocations of applied lower body negative pressure (LBNP): a stepwise escalation protocol and a direct application protocol, to simulate gradual and acute blood loss. The main outcome measure was CR time. Systolic, diastolic, and mean arterial pressures, heart rate, cardiac output, and systemic vascular resistance were measured continuously. CR time was assessed on the finger pulp using a standardized pressure and measured with a polarized reflectance imaging system., Results: The provocation elicited pre-syncope reactions and clear decrease in blood pressure for all participants, yet two-thirds of the participants in both protocols reacted with shorter CR times at maximum provocation, and the overall median CR time decreased by 0.2 s (Wilcoxon W = - 395.0, range: - 6.3 to 3.2, IQR - 1.3 to 0.1, P = 0.0070). Participants with shorter CR times exhibited comparatively greater increases in systemic vascular resistance and a more pronounced decrease in cardiac output., Conclusions: Our findings reveal that finger CR time paradoxically decreases in a majority of healthy volunteers in a lower body negative pressure model of blood loss, challenging traditional assumptions about the CR test's reliability as a shock indicator in its present interpretation., Competing Interests: Declarations. Ethics approval and consent to participate: This study adhered to the principles outlined in the Declaration of Helsinki regarding ethical standards for research involving human subjects. The study protocol was approved by the Swedish Ethical Review Authority (approval numbers 2020-00140, 2022-04442-02, and 2023-02922-02), and written informed consent was obtained from all participants. Consent for publication: All participants gave written consent for publication. Competing interest: The authors declare no conflicts of interest., (© 2025. The Author(s).)

Hydrogen bonds involving the oxygen atoms of intermediates that result from copper-mediated O 2 activation play a key role for controlling the reactivity of Cu x /O 2 active sites in metalloenzymes and synthetic model complexes. However, structural insight into H-bonding in such transient species as well as thermodynamic information about proton transfer to or from the O 2 -derived ligands is scarce. Here we present a detailed study of the reversible interconversion of a μ 1,2 -peroxodicopper(II) complex ([1] + ) and its μ 1,1 -hydroperoxo congener ([2] + ) via (de)protonation, including the isolation and structural characterization of several H-bond donor (HBD) adducts of [1] + and the determination of binding constants. For one of these adducts a temperature-dependent μ 1,2 -peroxo/μ 1,1 -hydroperoxo equilibrium associated with reversible H + -translocation is observed, its thermodynamics investigated experimentally and computationally, and effects of H-bonding on spectroscopic parameters of the Cu II 2 (μ 1,2 -O 2 ) species are revealed. DFT calculations allowed to fully map and correlate the trajectories of H + -transfer and μ 1,2 -peroxo→μ 1,1 -peroxo rearrangement. These findings enhance our understanding of two key intermediates in bioinspired Cu 2 /O 2 chemistry., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Digital learning resources are in increasing demand, especially in the light of the planned reform of the medical licensing regulations for 2028. In a pilot project, we digitised and evaluated a logbook for students in their practical year (PJ).The aim of this study is to evaluate the digital and non-digital PJ logbooks.Based on a printed PJ logbook, a digital PJ logbook was developed as a web app. The implementation was performed using the commercial enterprise knowledge management system Confluence (Atlassian Corporation, Sydney, Australia), which allows responsive design, integration with the university's user directory, and incorporation of corporate design. Student satisfaction (n = 34) was assessed using questionnaires and a 5-level Likert scale. Additionally, students self-assessed their skills at the beginning and end of the rotation before (n = 49) and after (n = 34) the introduction of the digital logbook by grade points.The majority of students found the digital logbook to be an intuitive and a valuable addition. In the stationary setting, the introduction of the digital logbook led to a significant improvement in self-assessed skills by 0.73 grade points at the beginning (p < 0.001) and 0.78 grade points at the end of the rotation (p < 0.001). In the operating theatre, there was only a significant improvement of 0.47 grade points at the beginning of the rotation (p = 0.027).The evaluation demonstrates that the digital PJ logbook is well-received by students and significantly improves their self-assessed skills. The observed increase in self-assessed skills could be attributed to the introduction of the digital logbook and its contents, although other factors, such as the engagement of the instructors, cannot be excluded. Future modifications are planned to make the logbook more appealing., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

There has been a lot of discussion on the technical aspects of the soon to be implemented European Union's Health Technology Assessment (EU HTA) regulation. However, there has been limited discussion on the implementation aspects and the potential limitations from a policy perspective. In May 2024, a group of HTA experts with previous policy responsibilities met in Rome to propose some policy aspects to be considered. As a result of the discussion, several proposals were made. Building mutual trust, improving collaboration and engaging all relevant stakeholders seems a must. Equally important are the communication aspects, and ensuring equal commitment by all parties, allocating the appropriate incentives at all levels. Finally, it is noted that the EU HTA regulation has to be seen from the perspective of a wider policy change within the large EU legal framework., Competing Interests: Conflict of interest: None of the participants declares any conflict of interest. FM, IL, and PL-C received participation fees for attending the meeting., (© 2025 The Authors.)

Although Emergency Medicine is now globally an established specialty, the Nordic countries have been relatively slow to implement it into their health care systems. To facilitate the development of EM in the Nordic area, a working group was formed with representation from all national EM societies; DASEM (Danish Society for Emergency Medicine), FiSEM (Finnish Society of Emergency Medicine), ISEM (Icelandic Society for Emergency Medicine), NCEM (Norwegian College of Emergency Medicine), and SWESEM (Swedish Society for Emergency Medicine). This group was tasked with creating a Nordic EM manifesto-to create a definition and developmental goals for Nordic Emergency Medicine. The commentary provides an overview of the current status and challenges facing EM in the Nordic countries., Competing Interests: Declarations. Competing interest: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Machine learning (ML) is increasingly used to predict clinical deterioration in intensive care unit (ICU) patients through scoring systems. Although promising, such algorithms often overfit their training cohort and perform worse at new hospitals. Thus, external validation is a critical - but frequently overlooked - step to establish the reliability of predicted risk scores to translate them into clinical practice. We systematically reviewed how regularly external validation of ML-based risk scores is performed and how their performance changed in external data., Methods: We searched MEDLINE, Web of Science, and arXiv for studies using ML to predict deterioration of ICU patients from routine data. We included primary research published in English before December 2023. We summarised how many studies were externally validated, assessing differences over time, by outcome, and by data source. For validated studies, we evaluated the change in area under the receiver operating characteristic (AUROC) attributable to external validation using linear mixed-effects models., Results: We included 572 studies, of which 84 (14.7%) were externally validated, increasing to 23.9% by 2023. Validated studies made disproportionate use of open-source data, with two well-known US datasets (MIMIC and eICU) accounting for 83.3% of studies. On average, AUROC was reduced by -0.037 (95% CI -0.052 to -0.027) in external data, with more than 0.05 reduction in 49.5% of studies., Discussion: External validation, although increasing, remains uncommon. Performance was generally lower in external data, questioning the reliability of some recently proposed ML-based scores. Interpretation of the results was challenged by an overreliance on the same few datasets, implicit differences in case mix, and exclusive use of AUROC., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Isostructural Dy(III) and Er(III) complexes [L 1 2 Ln(H 2 O) 5 ][I] 3  ⋅ L 1 2  ⋅ (CH 2 Cl 2 ) (Ln=Dy (1), Er (3)) and [L 2 2 Ln(H 2 O) 5 ][I] 3  ⋅ L 2 2  ⋅ (CH 2 Cl 2 ) 2 (Ln=Dy (2), Er (4)), with distorted pentagonal bipyramidal geometry (D 5h ) around the central metal were synthesized by utilizing two bulky phosphonamide ligands, adamantyl phosphonamide, (Ad)P(O)(NH i Pr) 2 (L 1 ) and carbazolyl phosphoramide (Cz)P(O)(NH i Pr) 2 (L 2 ). The resultant complexes were investigated for their magnetic properties in order to elucidate the impact of modification of the coordinating P-O bond environment either by increasing steric bulk and/or introduction of a third P-N bond at the central phosphorus atom. Magnetic studies revealed substantial energy barriers (U eff ) of 640 K and 491 K for Dy compounds 1 and 2, respectively, rendering them as some of the best-performing air-stable SIMs amongst the class of SIMs with D 5h symmetry. Compounds 1 and 2 exhibit magnetization blocking (T B ) at 6.5 K and 6 K, respectively, at a sweep rate of 20 Oe/s. Compound 1 benefits from increased lattice intermetallic distances due to bulky adamantyl substituent, but exhibits a significant deviation from linear axial (P)O-Dy-O(P) geometry (173.7(1)°). In addition to the deviation from linearity, the incorporation of a bulky adamantane (or carbazole) ligand in complex 1 (or 2) was found to result in relatively strong Dy…H-C agostic interactions, with distances of 3.698 Å (3.376 Å). These interactions are expected to induce transverse anisotropy. Ab initio CASSCF/RASSI-SO/SINGLE&#95;ANISO calculations offer valuable insights into the dynamics of magnetic relaxation and the impact of axial bulkiness on the anisotropy of D 5h systems. Beyond highlighting the crucial role of crystal field and symmetry in achieving high-temperature SIMs, this study also explores how the secondary coordination sphere can be engineered to create novel SIMs., (© 2025 Wiley-VCH GmbH.)