In our toolbox of quantum gates for spin qubits, the SWAP-family gates based on Heisenberg exchange coupling are quite versatile: the SWAP gate can help solve the connectivity problem by realizing both short- and long-range spin state transfer, while the (Formula presented) gate is a basic two-qubit entangling gate. Here we demonstrate a SWAP gate in a double quantum dot in isotopically enriched silicon in the presence of a micromagnet. We achieve a two-orders-of-magnitude adjustable ratio between the exchange coupling J and the Zeeman energy difference ΔEz, overcoming a major obstacle for a high-fidelity SWAP gate. We also calibrate the single-qubit local phases, evaluate the logical-basis fidelity of the SWAP gate, and further analyze the dominant error sources. These results pave the way for high-fidelity SWAP gates and processes based on them, such as quantum communication on chip and quantum simulation.@en

Detection and control of Andreev bound states (ABSs) localized at semiconductor-superconductor interfaces are essential for their use in quantum applications. Here we investigate the impact of ABSs on the supercurrent through a Josephson junction containing a quantum dot (QD). Additional normal-metal tunneling probes on both sides of the junction unveil the ABSs residing at the semiconductor-superconductor interfaces. Such knowledge provides an ingredient missing in previous studies, improving the connection between theory and experimental data. By varying the ABS energies using electrostatic gates, we show control of the switching current, with the ability to alter it by more than an order of magnitude. Finally, the large degree of ABS tunability allows us to realize a three-site Andreev molecule in which the central QD is screened by both ABSs. This system is studied simultaneously using both supercurrent and spectroscopy.@en

The synthesis of life from non-living matter has captivated and divided scientists for centuries. This bold goal aims at unraveling the fundamental principles of life and leveraging its unique features, such as its resilience, sustainability, and ability to evolve. Synthetic life represents more than an academic milestone—it has the potential to revolutionize biotechnology, medicine, and materials science. Although the fields of synthetic biology, systems chemistry, and biophysics have made great strides toward synthetic life, progress has been hindered by social, philosophical, and technical challenges, such as vague goals, misaligned interdisciplinary efforts, and incompletely addressing public and ethical concerns. Our perspective offers a roadmap toward the synthesis of life based on discussions during a 2-week workshop with scientists from around the globe.

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Background: Despite several randomised controlled trials (RCTs) on the use of adjuvant treatment with corticosteroids in patients with community-acquired pneumonia (CAP), the effect of this intervention on mortality remains controversial. We aimed to evaluate heterogeneity of treatment effect (HTE) of adjuvant treatment with corticosteroids on 30-day mortality in patients with CAP. Methods: In this individual patient data meta-analysis, we included RCTs published before July 1, 2024, comparing adjuvant treatment with corticosteroids versus placebo in patients hospitalised with CAP. The primary endpoint was 30-day all-cause mortality, collected across all trials, and analyses followed the intention-to-treat principle. We analysed HTE using risk and effect modelling. For risk modelling, patients were classified as having less severe or severe CAP based on the pneumonia severity index (PSI), comparing PSI class I–III versus class IV–V. For effect modelling, we trained a corticosteroid-effect model on six trials and externally validated it using data from two trials, received after model preregistration. This model classified patients into two groups: no predicted benefit and predicted benefit from adjuvant treatment with corticosteroids. The literature search was registered on PROSPERO, CRD42022380746. Findings: We included eight RCTs with 3224 patients. Across all eight trials, 246 (7·6%) patients died within 30 days (106 [6·6%] of 1618 in the corticosteroid group vs 140 [8·7%] of 1606 in the placebo group; odds ratio [OR] 0·72 [95% CI 0·56–0·94], p=0·017). The corticosteroid-effect model, which selected C-reactive protein (CRP), showed significant HTE during external validation in the two most recent trials. In these trials, 154 (11·4%) of 1355 patients died within 30 days (88 [13·1%] of 671 in the placebo group vs 66 [9·6%] of 684 in the corticosteroid group; OR 0·71 [95% CI 0·50–0·99], p=0·044). Among patients predicted to have no benefit (CRP ≤204 mg/L, n=725), no significant effect was observed (OR 0·98 [95% CI 0·63–1·50]), whereas for those with predicted benefit (CRP >204 mg/L, n=630), 39 (13·0%) of 301 patients died in the placebo group compared with 20 (6·1%) of 329 in the corticosteroid group (0·43 [0·25–0·76], p_interaction=0·026). No significant HTE was found between less severe CAP (PSI class I–III, n=229) and severe CAP (PSI class IV–V, n=1126). Corticosteroid therapy significantly increased hyperglycaemia risk (44 [12·8%] of 344 in the placebo group vs 84 [24·8%] of 339 in the corticosteroid group; OR 2·50 [95% CI 1·63–3·83], p<0·0001) and hospital re-admission risk (30 [3·7%] of 814 in the placebo group vs 57 [7·0%] of 819 in the corticosteroid group; 1·95 [1·24–3·07], p=0·0038). Interpretation: Overall, adjuvant therapy with corticosteroids significantly reduces 30-day mortality in patients hospitalised with CAP. The treatment effect varied significantly among subgroups based on CRP concentrations, with a substantial mortality reduction observed only in patients with high baseline CRP. Funding: None.

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Dual reporters encoding two distinct proteins within the same mRNA have had a crucial role in identifying and characterizing unconventional mechanisms of eukaryotic translation. These mechanisms include initiation via internal ribosomal entry sites (IRESs), ribosomal frameshifting, stop codon readthrough and reinitiation. This design enables the expression of one reporter to be influenced by the specific mechanism under investigation, while the other reporter serves as an internal control. However, challenges arise when intervening test sequences are placed between these two reporters. Such sequences can inadvertently impact the expression or function of either reporter, independent of translation-related changes, potentially biasing the results. These effects may occur due to cryptic regulatory elements inducing or affecting transcription initiation, splicing, polyadenylation and antisense transcription as well as unpredictable effects of the translated test sequences on the stability and activity of the reporters. Unfortunately, these unintended effects may lead to misinterpretation of data and the publication of incorrect conclusions in the scientific literature. To address this issue and to assist the scientific community in accurately interpreting dual-reporter experiments, we have developed comprehensive guidelines. These guidelines cover experimental design, interpretation and the minimal requirements for reporting results. They are designed to aid researchers conducting these experiments as well as reviewers, editors and other investigators who seek to evaluate published data.@en

More than ten ergot alkaloids comprising both natural and semi-synthetic products are used to treat various diseases^1,2. The central C ring forms the core pharmacophore for ergot alkaloids, giving them structural similarity to neurotransmitters, thus enabling their modulation of neurotransmitter receptors³. The haem catalase chanoclavine synthase (EasC) catalyses the construction of this ring through complex radical oxidative cyclization⁴. Unlike canonical catalases, which catalyse H₂O₂ disproportionation^5,6, EasC and its homologues represent a broader class of catalases that catalyse O₂-dependent radical reactions^4,7. We have elucidated the structure of EasC by cryo-electron microscopy, revealing a nicotinamide adenine dinucleotide phosphate (reduced) (NADPH)-binding pocket and a haem pocket common to all haem catalases, with a unique homodimeric architecture that is, to our knowledge, previously unobserved. The substrate prechanoclavine unprecedentedly binds in the NADPH-binding pocket, instead of the previously suspected haem-binding pocket, and two pockets were connected by a slender tunnel. Contrary to the established mechanisms, EasC uses superoxide rather than the more generally used transient haem iron–oxygen complexes (such as compounds I, II and III)^8,9, to mediate substrate transformation through superoxide-mediated cooperative catalysis of the two distant pockets. We propose that this reactive oxygen species mechanism could be widespread in metalloenzyme-catalysed reactions.

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In this article Reference 10 was incorrect as ‘van der Zwanenburg LC, Koldenhof JJ, Suijkerbuijk KPM, Schellekens MPJ (2024) What patients with advanced cancer experience as helpful in navigating their life with a long-term response: a qualitative study. Support Care Cancer 32(4):222’ and should have been ‘Zwanenburg LC, van der Lee ML, Koldenhof JJ, Suijkerbuijk KPM, Schellekens MPJ (2024) What patients with advanced cancer experience as helpful in navigating their life with a long-term response: a qualitative study. Support Care Cancer. 32(4):222. PMID: 38470541.’@en

The publisher regrets that one of the authors is missing in the PDF and web version of the article. Namely, Anton Bouter, who is affiliated with the Centrum Wiskunde & Informatica as described above in this erratum. In table 1, a space is missing after the character “<” in the line `Cervix -> Sigmoid' in column `Sparing criteria'. In table 3, the `%' signs in first column (DVI) should also be in subscript, similar to how it is written in the first column of Table 4. The supplementary material should state that needle contribution is limited to up to 40% of the total given dwell time (in applicator and needles). Lastly, the article should be seen as a research article and the authors would like to be cited as “L.R.M. Dickhoff and R.J. Scholman et al”.

The publisher would like to apologise for any inconvenience caused.@en

Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and microscopy holds potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing software solutions for MALDI MSI data analysis are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries. Here, we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data. msiFlow integrates all necessary steps from raw data import to analytical visualisation along with state-of-the-art and self-developed algorithms into automated workflows. Using msiFlow, we unravel the molecular heterogeneity of leukocytes in infected tissues by spatial regulation of ether-linked phospholipids containing arachidonic acid. We anticipate that msiFlow will facilitate the broad applicability of MSI in multimodal imaging to uncover context-dependent cellular regulations in disease states.

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Cardiac magnetic resonance imaging (MRI) provides detailed and quantitative evaluation of the heart’s structure, function, and tissue characteristics with high-resolution spatial–temporal imaging. However, its slow imaging speed and motion artifacts are notable limitations. Undersampling reconstruction, especially data-driven algorithms, has emerged as a promising solution to accelerate scans and enhance imaging performance using highly under-sampled data. Nevertheless, the scarcity of publicly available cardiac k-space datasets and evaluation platform hinder the development of data-driven reconstruction algorithms. To address this issue, we organized the Cardiac MRI Reconstruction Challenge (CMRxRecon) in 2023, in collaboration with the 26th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI). CMRxRecon presented an extensive k-space dataset comprising cine and mapping raw data, accompanied by detailed annotations of cardiac anatomical structures. With overwhelming participation, the challenge attracted more than 285 teams and over 600 participants. Among them, 22 teams successfully submitted Docker containers for the testing phase, with 7 teams submitted for both cine and mapping tasks. All teams use deep learning based approaches, indicating that deep learning has predominately become a promising solution for the problem. The first-place winner of both tasks utilizes the E2E-VarNet architecture as backbones. In contrast, U-Net is still the most popular backbone for both multi-coil and single-coil reconstructions. This paper provides a comprehensive overview of the challenge design, presents a summary of the submitted results, reviews the employed methods, and offers an in-depth discussion that aims to inspire future advancements in cardiac MRI reconstruction models. The summary emphasizes the effective strategies observed in Cardiac MRI reconstruction, including backbone architecture, loss function, pre-processing techniques, physical modeling, and model complexity, thereby providing valuable insights for further developments in this field.@en

To counteract hand, foot, and mouth disease-causing viruses such as enterovirus A71 and coxsackievirus A6, virus-like particles (VLPs) have emerged as a leading contender for the development of a multivalent vaccine. However, VLPs have shown rapid conversion from a highly immunogenic state to a less immunogenic state and low particle integrity lifetimes compared to inactivated virus vaccines, thus raising concerns about their overall stability. Here, we produce VLPs to investigate capsid stability using cryogenic electron microscopy (cryo-EM), mass spectrometry (MS), biochemical assays, and atomic force microscopy (AFM). In contrast to prior studies and prevailing hypotheses, we show that insect-cell produced enterovirus VLPs include encapsidated RNA fragments with viral protein coding sequences. Our integrated approach reveals that CVA6 VLPs do not undergo viral maturation, in contrast to virions; that they can encapsidate RNA fragments, similarly to virions; and that despite the latter, they are more brittle than virions. Interestingly, this indicates that CVA6 VLP stability is more affected by lack of viral maturation than the presence of RNA. Our study highlights how the development of VLPs as vaccine candidates should encompass probing for unwanted (viral) RNA content and establishing control of their maturation to enhance stability.@en

Stratospheric aerosol injection could mitigate harmful effects of global warming, but could have undesirable side effects, such as warming the stratosphere and depleting the ozone layer. We explore the potential benefits of solid alumina and calcite particles as alternatives to sulfate aerosols by using an experimentally informed aerosol-chemistry-climate model. Compared to sulfur dioxide, injection of solids reduces stratospheric warming by up to 70% and diffuse radiation by up to 40%, highlighting their potential benefits. Achieving −1 W m⁻² of radiative forcing would likely result in very small ozone changes, but sizable uncertainties remain. These arise from poorly understood heterogeneous chemical and microphysical processes, which, under less likely assumptions, could lead to larger global ozone column changes between −14% and +4%. Our work provides recommendations for improving the understanding of stratospheric aerosol injection using materials other than sulfur dioxide, and underscores the need for kinetic laboratory studies.

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Objective: To investigate whether local lesions created by stereo-electroencephalography (SEEG)–guided radiofrequency thermocoagulation (RFTC) affect distant brain connectivity and excitability in patients with focal, drug-resistant epilepsy (DRE). Methods: Ten patients with focal DRE underwent SEEG implantation and subsequently 1 Hz bipolar repetitive electrical stimulation (RES) for 30 s before and after RFTC. Root mean square (RMS) of cortico-cortical evoked potentials (CCEPs) was calculated for 15 ms to 300 ms post-stimulation with baseline correction. Contact pairs were categorized as both coagulated, hybrid, or both non-coagulated. The data were divided into nine categories based on the stimulating and recording contact pair combinations. RMS of CCEPs was compared before and after (<12 h) RFTC using a two-sample t test (Hochberg corrected, p < 0.05) for each patient. Boost score, indicating power increase during seizures before RFTC relative to baseline, was analyzed in 4 s windows with 1 s overlap during seizure duration. Results: RFTC altered connectivity across all categories. Of interest, decreases and increases in RMS were observed in connections between non-coagulated contacts distant from coagulation site (range: 1.09–85 mm, median = 17.7 mm, interquartile range [IQR] 10.1–32.3). Contact pairs involved in significantly altered non-coagulated connections showed a higher boost score correlation in the theta, beta, and gamma bands, as well as a stronger maximum correlation with coagulated sites in the delta band than contacts for which connectivity did not change after RFTC. Significance: This study highlights how local lesions alter distant brain connectivity, providing insights for future research on epilepsy network changes and seizure outcomes following RFTC.

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Randomized controlled trials (RCTs) are the cornerstone of modern evidence-based medicine. They are considered essential to establish definitive evidence of efficacy and safety for new drugs, and whenever possible they should also be the preferred method for investigating new high-risk medical devices. Well-designed studies robustly inform clinical practice guidelines and decision-making, but administrative obstacles have made it increasingly difficult to conduct informative RCTs. The obstacles are compounded for RCTs of high-risk medical devices by extra costs related to the interventional procedure that is needed to implant the device, challenges with willingness to randomize patients throughout a trial, and difficulties in ensuring proper blinding even with sham procedures. One strategy that may help is to promote the wider use of simpler and more streamlined RCTs using data that are collected routinely during healthcare delivery. Recent large simple RCTs have successfully compared the performance of drugs and of high-risk medical devices, against alternative treatments; they enrolled many patients in a short time, limited costs, and improved efficiency, while also achieving major impact. From a task conducted within the CORE-MD project, we report from our combined experience of designing and conducting large pharmaceutical trials during the COVID-19 pandemic, and of planning and coordinating large registry-based RCTs of cardiovascular devices. We summarize the essential principles and utility of large simple RCTs, likely applicable to all interventions but especially in order to promote their wider adoption to evaluate new medical devices.@en

TiO₂ nanoparticles (NPs) are extensively used in various applications, highlighting the importance of ongoing research into their effects. This work belongs among rare whole-body inhalation studies investigating the effects of TiO₂ NPs on mice. Unlike previous studies, the concentration of TiO₂ NPs in the inhalation chamber (130.8 μg/m³) was significantly lower. This 11-week study on mice confirmed in vivo the presence of TiO₂ NPs in lung macrophages and type II pneumocytes including their intracellular localization by using the electron microscopy and the state-of-the-art methods detecting NPs' chemical identity/crystal structure, such as the energy-dispersed X-ray spectroscopy (EDX), cathodoluminescence (CL), and detailed diffraction pattern analysis using powder nanobeam diffraction (PNBD). For the first time in inhalation study in vivo, the alterations in erythrocyte morphology with evidence of echinocytes and stomatocytes, accompanied by iron accumulation in spleen, liver, and kidney, are reported following NP's exposure. Together with the histopathological evidence of hyperaemia in the spleen and kidney, and haemosiderin presence in the spleen, the finding of NPs containing iron might suggest the increased decomposition of damaged erythrocytes. The detection of TiO₂ NPs on erythrocytes through CL analysis confirmed their potential systemic availability. On the contrary, TiO₂ NPs were not confirmed in other organs (spleen, liver, and kidney); Ti was detected only in the kidney near the detection limit.

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Third-generation gravitational wave detectors will use large mirrors isolated from seismic motion at low frequency, and also cooled down to cryogenic temperatures. To fulfil these two specifications, the E-TEST project explores the possibility of using a purely non-contact radiative cooling strategy. Based on cooling predictions, the paper includes a detailed design of the cryostat and the assembly procedure. A test campaign demonstrated that the proposed strategy succeeded in bringing the temperature of a Image 1 dummy mirror down to Image 2 in 19 days. These encouraging results are paving the way toward a fully radiative approach for cooling the mirrors of the future Einstein Telescope.@en

The European Union's goal of achieving climate neutrality by 2050, outlined in the European Green Deal, is supported by numerous studies providing insights into pathways and emission reduction strategies in the energy sectors. However, model comparisons of such pathways are less common due to the complex nature of climate and energy modelling. Our study brings together integrated assessment models and energy system models under a common framework to develop EU policy scenarios: a Current Trends scenario reflecting existing policies and trends and a Climate Neutrality scenario aligned with the EU's emission reduction target. Both scenarios project reduced final energy consumption by 2050, driven by increased electrification and decreased fossil fuel usage. Electricity consumption increases driven by electrification despite the improved efficiency of electrified technologies. Models align on a shift toward renewables but diverge in technology and fuel choices, reflecting various approaches to reach net-zero energy systems. Furthermore, trade-offs between energy demand and supply mitigation strategies, as well as between renewable energy, e-fuels, and CCS technologies are identified. Considering these model variations, our study highlights the importance of consistent model comparison to offer reliable recommendations to policymakers and stakeholders. We conclude that model diversity is a valuable asset when used sensibly.@en

Recycling-oriented alloy design is a crucial part of material sustainability, as it reduces the need for raw material extraction and minimises environmental impact. This requires that scraps be reused or repurposed effectively, even when the scraps are co-mingled and have higher costs for further sorting and separation. In this work, we explore an alloy design concept by creating a compositionally flexible domain that can recycle multiple alloy grades and yet maintain relatively consistent properties across chemical variations. This is demonstrated through the Fe-Cr-Ni-Mn system to identify compositionally flexible austenitic stainless steels (CF-ASS) and accommodate the recycling of mixed austenitic stainless steel scraps. Alloys within the nominal composition spaces exhibit relatively consistent mechanical properties and corrosion resistance despite significant variations in different alloy compositions. We illustrate how we can utilise the compositionally flexible austenitic stainless steels to recycle mixed 200 and 300-series stainless steel and ferronickel scraps, demonstrating its practical viability. While this demonstration focuses on the stainless steel system, the underlying principles can be extended to other systems related to mixed scrap recycling.

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Low-loss deposited dielectrics are beneficial for the advancement of superconducting integrated circuits for astronomy. In the microwave band (approximately 1-10 GHz) the dielectric loss at cryogenic temperatures and low electric field strengths is dominated by two-level systems. However, the origin of the loss in the millimeter-submillimeter band (approximately 0.1-1 THz) is not understood. We measured the loss of hydrogenated-amorphous-SiC films in the 0.27-100-THz range using superconducting-microstrip resonators and Fourier-transform spectroscopy. The agreement between the loss data and a Maxwell-Helmholtz-Drude dispersion model suggests that vibrational modes above 10 THz dominate the loss in hydrogenated amorphous SiC above 200 GHz.

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Research into the impact of innovative sustainable energy experiments and demonstrations is crucial to diversifying, scaling up, and accelerating the sustainable energy transition. Although there is vast research into sustainable energy experiments and demonstrations, research literature offers a fragmented collection of findings. A coherent overview of themes and insights regarding the transformative impact of innovative sustainable energy experiments and demonstrations on sustainable energy systems from the past, present, and near future is lacking and necessary to increase experiments and demonstrations' impact on the sustainable energy transition. The research in this study fills this knowledge gap by providing such an overview and yields novel insights into the organized function and impact of experiments and demonstrations. It spans a broad spectrum of sustainable energy technologies, the empirical domains where these are invented, developed and applied, and the stakeholders involved. The overview is the outcome of a Delphi study in which the insights of 47 international scientific research experts in sustainable energy experiments and demonstrations are bundled and explained. This study presents a thematic overview of the significant insights regarding past and current sustainable energy experiments and demonstrations and outlines a research agenda for the future. Policymakers, practitioners, and scientists can leverage this to inform their sustainable energy policies, business strategies, and research programs.@en