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Massive stars lead the ionization and mechanical feedback within young star-forming regions. The Large Magellanic Cloud (LMC) is an ideal galaxy for studying individual massive stars and quantifying their feedback contribution to the environment. We analyze eight exemplary targets in LMC N11 B from the Hubble UV Legacy Library of Young Stars as Essential Standards (ULLYSES) program, using novel spectra from HST (COS and STIS) in the UV, and from VLT (X-shooter) in the optical. We model the spectra of early to late O-type stars by using state-of-the-art PoWR atmosphere models. We determine the stellar and wind parameters (e.g., $T_\star$, $\log g$, $L_{\star}$, $\dot{M}$, $v_\infty$) of the analyzed objects, chemical abundances (C, N, O), ionizing and mechanical feedback ($Q_\mathrm{H}$, $Q_\mathrm{He{\small{I}}}$, $Q_\mathrm{He{\small{II}}}$, $L_\mathrm{mec}$) and X-rays. We report ages of $2-4.5$ Myr and masses of $30-60$ $M_\odot$ for the analyzed stars in N11 B, consistent with a scenario of sequential star formation. We note that the observed wind-momentum luminosity relation is consistent with theoretical predictions. We detect nitrogen enrichment in most of the stars, up to a factor of seven. However, we do not find a correlation between nitrogen enrichment and projected rotational velocity. Finally, based on their spectral type, we estimate the total ionizing photons injected from the O-type stars in N11 B into its environment. We report $\log$ ($\sum$ $Q_\mathrm{H}$)$=50.5$ ph s$^{-1}$, $\log$ ($\sum$ $Q_\mathrm{He{\small{I}}}$)$=49.6$ ph s$^{-1}$ and $\log$ ($\sum$ $Q_\mathrm{He{\small{II}}}$)$=44.4$ ph s$^{-1}$, consistent with the total ionizing budget in N11., Comment: Accepted in Astronomy and Astrophysics

Mass loss through a stellar wind is an important physical process that steers the evolution of massive stars and controls the properties of their end-of-life products, such as the supernova type and the mass of compact remnants. For an accurate mass loss determination, the inhomogeneities in the wind, known as clumping, needs to be taking into account. We aim to improve empirical estimates of mass loss and wind clumping for hot main-sequence massive stars, study the dependence of both properties on the metallicity, and compare the theoretical predictions to our findings. We analyzed the optical and UV spectra of 13 O-type stars in the Small Magellanic Cloud galaxy, which has a metallicity of $\sim 0.2\,Z_\odot$. We quantified the stellar atmosphere, outflow, and wind-clumping properties. To probe the role of metallicity, we compared our findings to studies of Galactic and Large Magellanic Cloud samples that were analyzed with similar methods. We find significant variations in the wind-clumping properties of the target stars, with clumping starting at flow velocities $0.01 - 0.23$ of the terminal wind velocity and reaching clumping factors $f_{\rm cl} = 2 - 30$. In the luminosity ($\log L / L_{\odot} = 5.0 - 6.0$) and metallicity ($Z/Z_{\odot} = 0.2 - 1$) range we considered, we find that the scaling of the mass loss $\dot{M}$ with metallicity $Z$ varies with luminosity. At $\log L/L_{\odot} = 5.75$, we find $\dot{M} \propto Z^m$ with $m = 1.02 \pm 0.30$, in agreement with pioneering work in the field. For lower luminosities, however, we obtain a significantly steeper scaling of $m > 2$. The monotonically decreasing $m(L)$ behavior adds a complexity to the functional description of the mass-loss rate of hot massive stars. Although the trend is present in the predictions, it is much weaker than we found here., Comment: 37 pages, 29 figures. Accepted for publication in Astronomy and Astrophysics

Melnick 34 (Mk 34) is one of the most massive binary systems known and is one of the brightest X-ray point sources in the 30 Doradus region. We investigated the impact of this massive system on the surrounding interstellar medium (ISM) using the optical spectroscopic capabilities of the narrow-field mode (NFM) of the Multi-Unit Spectroscopic Explorer (MUSE). MUSE-NFM spatially resolved the ISM in the vicinity of Mk 34 with a resolution comparable to that of the HST. The analysis of the [NII]$\lambda$6583 and [SII]$\lambda$6717 emission lines reveals a cone-like structure apparently originating from Mk 34 and extending southeast. Electron density maps and radial velocity measurements of the ISM lines further support an outflow scenario traced by these emissions. While no clear northwestern counterpart to this outflow was observed, we note increased extinction in that direction, towards the R136 cluster. The ISM material along the projected diagonal of the outflow on both sides of Mk 34 shows similar properties in terms of the emission line ratios seen in the Baldwin-Phillips-Terlevich diagram. These results are consistent across two observational epochs. Additionally, we examined the residual maps within a 0.5" radius of Mk 34 after modeling and subtracting the point spread function. The observed variations in the residuals could potentially be linked to Mk 34's known periodic behavior. However, further observations with appropriate cadence are needed to fully monitor the 155 day periodicity of Mk 34's X-ray emissions., Comment: 9 pages, 10 figures. Accepted in A&A

Context. Current implementations of mass loss for hot, massive stars in stellar evolution models include a sharp increase in mass loss when blue supergiants become cooler than Teff 20-22kK. This drastic mass-loss jump has been motivated by the potential presence of a so-called bistability ionisation effect, which may occur for line-driven winds in this temperature region due to recombination of important line-driving ions. Aims. We perform quantitative spectroscopy using UV (ULLYSES program) and optical (XShootU collaboration) data for 17 OB-supergiant stars in the LMC (covering the range Teff 14-32kK), deriving absolute constraints on global stellar, wind, and clumping parameters. We examine whether there are any empirical signs of a mass-loss jump in the investigated region, and we study the clumped nature of the wind. Methods. We use a combination of the model atmosphere code fastwind and the genetic algorithm code Kiwi-GA to fit synthetic spectra of a multitude of diagnostic spectral lines in the optical and UV. Results. We find no signs of any upward mass loss jump anywhere in the examined region. Standard theoretical comparison models, which include a strong bistability jump thus severely over predict the empirical mass-loss rates on the cool side of the predicted jump. Additionally, we find that on average about 40% of the total wind mass seems to reside in the diluted medium in between dense clumps. Conclusions. Our derived mass-loss rates suggest that for applications like stellar evolution one should not include a drastic bistability jump in mass loss for stars in the temperature and luminosity region investigated here. The derived high values of interclump density further suggest that the common assumption of an effectively void interclump medium (applied in the vast majority of spectroscopic studies of hot star winds) is not generally valid in this parameter regime.

Target selection is crucial in pharmaceutical drug discovery, directly influencing clinical trial success. Despite its importance, drug development remains resource-intensive, often taking over a decade with significant financial costs. High failure rates highlight the need for better early-stage target selection. We present GATher, a graph attention network designed to predict therapeutic gene-disease links by integrating data from diverse biomedical sources into a graph with over 4.4 million edges. GATher incorporates GATv3, a novel graph attention convolution layer, and GATv3HeteroConv, which aggregates transformations for each edge type, enhancing its ability to manage complex interactions within this extensive dataset. Utilizing hard negative sampling and multi-task pre-training, GATher addresses topological imbalances and improves specificity. Trained on data up to 2018 and evaluated through 2024, our results show GATher predicts clinical trial outcomes with a ROC AUC of 0.69 for unmet efficacy failures and 0.79 for positive efficacy. Feature attribution methods, using Captum, highlight key nodes and relationships, enhancing model interpretability. By 2024, GATher improved precision in prioritizing the top 200 clinical trial targets to 14.1%, an absolute increase of over 3.5% compared to other methods. GATher outperforms existing models like GAT, GATv2, and HGT in predicting clinical trial outcomes, demonstrating its potential in enhancing target validation and predicting clinical efficacy and safety.

Surveys in the Milky Way and Large Magellanic Cloud revealed that the majority of massive stars will interact with companions during their lives. However, knowledge of the binary properties of massive stars at low metallicity, which approaches the conditions of the Early Universe, remains sparse. We present the Binarity at LOw Metallicity (BLOeM) campaign - an ESO large programme designed to obtain 25 epochs of spectroscopy for 929 massive stars in the SMC - the lowest metallicity conditions in which multiplicity is probed to date (Z = 0.2 Zsun). BLOeM will provide (i) the binary fraction, (ii) the orbital configurations of systems with periods P < 3 yr, (iii) dormant OB+BH binaries, and (iv) a legacy database of physical parameters of massive stars at low metallicity. The stars are observed with the LR02 setup of the giraffe instrument of the Very Large Telescope (3960-4570A, resolving power R=6200; typical signal-to-noise ratio S/N=70-100). This paper utilises the first 9 epochs obtained over a three-month time. We describe the survey and data reduction, perform a spectral classification of the stacked spectra, and construct a Hertzsprung-Russell diagram of the sample via spectral-type and photometric calibrations. The sample covers spectral types from O4 to F5, spanning the effective temperature and luminosity ranges 6.5

Context. B supergiants (BSGs) represent an important connection between the main sequence and more extreme evolutionary stages of massive stars. Additionally, lying toward the cool end of the hot star regime, determining their wind properties is crucial to constrain the evolution and feedback of massive stars as, for instance, they might manifest the bi-stability jump phenomenon. Aims. We undertake a detailed analysis of a representative sample of 18 Small Magellanic Cloud (SMC) BSGs within the ULLYSES and XShootU datasets. Our UV and optical analysis spans BSGs from B0 to B8 - covering the bi-stability jump region. We aim to evaluate their evolutionary status and verify what their wind properties say about the bi-stability jump in a low-metallicity environment. Methods. We used the CMFGEN to model the spectra and photometry (from UV to infrared) of our sample. We compare our results with different evolutionary models, with previous determinations in the literature of OB stars, and with diverging mass-loss recipes at the bi-stability jump. Additionally, we provide the first BSG models in the SMC including X-rays. Results. (i) Within a single-stellar evolution framework, the evolutionary status of early BSGs seem less clear than that of late BSGs, which agree with H-shell burning models. (ii) UV analysis shows evidence that BSGs contain X-rays in their atmospheres, for which we provide constraints. In general, we find higher X-ray luminosity (close to the standard log(L_X/L) ~ -7) for early BSGs. For cooler BSGs, lower values are preferred, log(L_X/L) ~ -8.5. (iii) The obtained mass-loss rates suggest neither a jump nor a monotonic decrease with temperature. Instead, a rather constant trend is observed, which is at odds with the increase found for Galactic BSGs. (iv) The wind velocity behavior with temperature shows a sharp drop at ~19 kK, similar to what is observed for Galactic BSGs., Comment: 33 pages (23+10)+(22 at Zenodo), 34 figures (21+13)+(21 at Zenodo), 7 tables (3+4)+(1 at Zenodo), accepted for publication

CONTEXT: The spectral analysis of hot, massive stars is a fundamental astrophysical method to obtain their intrinsic properties and their feedback. Quantitative spectroscopy for hot, massive stars requires detailed numerical modeling of the atmosphere and an iterative treatment to obtain the best solution within a given framework. AIMS: We present an overview of different techniques for the quantitative spectroscopy of hot stars employed within the X-Shooting ULLYSES collaboration, from grid-based approaches to tailored fits. By performing a blind test, we gain an overview about the similarities and differences of the resulting parameters. Our study aims to provide an overview of the parameter spread caused by different approaches. METHODS: For three different stars from the sample (SMC O5 star AzV 377, LMC O7 star Sk -69 50, and LMC O9 star Sk -66 171), we employ different atmosphere codes (CMFGEN, Fastwind, PoWR) and strategies to determine their best-fitting model. For our analyses, UV and optical spectra are used to derive the properties with some methods relying purely on optical data for comparison. To determine the overall spectral energy distribution, we further employ additional photometry from the literature. RESULTS: Effective temperatures for each of three sample stars agree within 3 kK while the differences in log g can be up to 0.2 dex. Luminosity differences of up to 0.1 dex result from different reddening assumptions, which seem to be larger for the methods employing a genetic algorithm. All sample stars are nitrogen-enriched. CONCLUSIONS: We find a reasonable agreement between the different methods. Tailored fitting tends to be able to minimize discrepancies obtained with more course or automatized treatments. UV spectral data is essential for the determination of realistic wind parameters. For one target (Sk -69 50), we find clear indications of an evolved status., Comment: 19+15 pages, 21+4 figures, accepted version (A&A 689, A30) including language editing, condensed abstract

On the route towards merging neutron stars and stripped-envelope supernovae, binary population synthesis predicts a large number of post-interaction systems with massive stars that have stripped off their outer layers. Yet, observations of such stars in the intermediate-mass regime below the Wolf-Rayet masses are rare. Using X-Shooting ULLYSES (XShootU) data, we discovered three partially stripped star + Be/Oe binaries in the Magellanic Clouds. We analyzed the UV and optical spectra using the PoWR model atmosphere code by superimposing model spectra corresponding to each component. The estimated current masses of the partially stripped stars fall within the intermediate mass range of 4-8 $M_{\odot}$. These objects are overluminous for their stellar masses, matching core He-burning luminosities. Their Be/Oe secondaries have much higher masses than their stripped primaries (mass ratio > 2). All three partially stripped stars show significant nitrogen enrichment and carbon and oxygen depletion on their surfaces. Additionally, one of our sample stars exhibits significant helium enrichment. Our study provides the first comprehensive determination of the wind parameters of partially stripped stars in the intermediate mass range. The wind mass-loss rates of these stars are found to be on the order of $10^{-7} M_\odot$ yr$^{-1}$, which is over ten times higher than that of OB stars of the same luminosity. Current evolutionary models characterizing this phase typically employ OB or WR mass-loss rates, which underestimate or overestimate stripped stars' mass-loss rates by an order of magnitude. Binary evolution models indicate that the observed primaries had initial masses of 12-17 $M_{\odot}$, making them potential candidates for stripped-envelope supernovae that form neutron stars. If they survive the explosion, these systems may become Be X-ray binaries and later double neutron stars., Comment: Accepted for publication in Astronomy & Astrophysics

Natural gestures are crucial for mid-air interaction, but predicting and managing muscle fatigue is challenging. Existing torque-based models are limited in their ability to model above-shoulder interactions and to account for fatigue recovery. We introduce a new hybrid model, NICER, which combines a torque-based approach with a new term derived from the empirical measurement of muscle contraction and a recovery factor to account for decreasing fatigue during rest. We evaluated NICER in a mid-air selection task using two interaction methods with different degrees of perceived fatigue. Results show that NICER can accurately model above-shoulder interactions as well as reflect fatigue recovery during rest periods. Moreover, both interaction methods show a stronger correlation with subjective fatigue measurement (r = 0.978/0.976) than a previous model, Cumulative Fatigue (r = 0.966/ 0.923), confirming that NICER is a powerful analytical tool to predict fatigue across a variety of gesture-based interactive applications.

Massive stars rotate faster, on average, than lower mass stars. Stellar rotation triggers hydrodynamical instabilities which transport angular momentum and chemical species from the core to the surface. Models of high-mass stars that include these processes predict that chemical mixing is stronger at lower metallicity. We aim to test this prediction by comparing the surface abundances of massive stars at different metallicities. We performed a spectroscopic analysis of single O stars in the Magellanic Clouds (MCs) based on the ULLYSES and XshootU surveys. We determined the fundamental parameters and helium, carbon, nitrogen, and oxygen surface abundances of 17 LMC and 17 SMC non-supergiant O6-9.5 stars. We complemented these determinations by literature results for additional MCs and also Galactic stars to increase the sample size and metallicity coverage. We investigated the differences in the surface chemical enrichment at different metallicities and compared them with predictions of three sets of evolutionary models. Surface abundances are consistent with CNO-cycle nucleosynthesis. The maximum surface nitrogen enrichment is stronger in MC stars than in Galactic stars. Nitrogen enrichment is also observed in stars with higher surface gravities in the SMC than in the Galaxy. This trend is predicted by models that incorporate chemical transport caused by stellar rotation. The distributions of projected rotational velocities in our samples are likely biased towards slow rotators. A metallicity dependence of surface abundances is demonstrated. The analysis of larger samples with an unbiased distribution of projected rotational velocities is required to better constrain the treatment of chemical mixing and angular momentum transport in massive single and binary stars., Comment: 15 pages + appendix. Accepted in Astronomy & Astrophysics

The Hubble Space Telescope has devoted 500 orbits to observing 250 massive stars with low metallicity in the ultraviolet (UV) range within the framework of the ULLYSES program. The X-Shooting ULLYSES (XShootU) project enhances the legacy value of this UV dataset by providing high-quality optical and near-infrared spectra, which are acquired using the wide-wavelength-coverage X-shooter spectrograph at ESO's Very Large Telescope. XShootU emphasises the importance of combining UV with optical spectra for the consistent determination of key stellar parameters such as effective temperature, surface gravity, luminosity, abundances, and wind characteristics including mass-loss rates as a function of metallicity. Since uncertainties in these parameters have implications across various branches of astrophysics, the data and modelling generated by the XShootU project are poised to significantly advance our understanding of massive stars at low metallicity. This is particularly crucial for confidently interpreting JWST data of the earliest stellar generations, making XShootU a unique resource for comprehending individual spectra of low-metallicity stars., Comment: 6 pages, 6 figures. ESO Large Programme Overview

Stepped wedge cluster-randomized trial (CRTs) designs randomize clusters of individuals to intervention sequences, ensuring that every cluster eventually transitions from a control period to receive the intervention under study by the end of the study period. The analysis of stepped wedge CRTs is usually more complex than parallel-arm CRTs due to more complex intra-cluster correlation structures. A further challenge in the analysis of closed-cohort stepped wedge CRTs, which follow groups of individuals enrolled in each period longitudinally, is the occurrence of dropout. This is particularly problematic in studies of individuals at high risk for mortality, which causes non-ignorable missing outcomes. If not appropriately addressed, missing outcomes from death will erode statistical power, at best, and bias treatment effect estimates, at worst. Joint longitudinal-survival models can accommodate informative dropout and missingness patterns in longitudinal studies. Specifically, within the joint longitudinal-survival modeling framework, one directly models the dropout process via a time-to-event submodel together with the longitudinal outcome of interest. The two submodels are then linked using a variety of possible association structures. This work extends linear mixed-effects models by jointly modeling the dropout process to accommodate informative missing outcome data in closed-cohort stepped wedge CRTs. We focus on constant intervention and general time-on-treatment effect parametrizations for the longitudinal submodel and study the performance of the proposed methodology using Monte Carlo simulation under several data-generating scenarios. We illustrate the methodology in practice by reanalyzing data from the `Frail Older Adults: Care in Transition' (ACT) trial, a stepped wedge CRT of a multifaceted geriatric care model versus usual care in 35 primary care practices in the Netherlands.

Using the medium resolution spectrograph X-shooter, spectra of 235 OB and Wolf-Rayet (WR) stars in sub-solar metallicity environments have been secured. [...]This second paper focuses on the optical observations of 232 Magellanic Clouds targets. It describes the uniform reduction of the UVB (300 - 560 nm) and VIS (550 - 1020 nm) XShootU data as well as the preparation of advanced data products [...] . The data reduction of the raw data is based on the ESO CPL X-shooter pipeline. We paid particular attention to the determination of the response curves [...] We implemented slit-loss correction, absolute flux calibration, (semi-)automatic rectification to the continuum, and a correction for telluric lines. The spectra of individual epochs were corrected for the barycentric motion, re-sampled and co-added, and the spectra from the two arms were merged into a single flux calibrated spectrum covering the entire optical range with maximum signal-to-noise ratio. [...] We provide three types of data products: (i) two-dimensional spectra for each UVB and VIS exposure; (ii) one-dimensional UVB and VIS spectra before and after response-correction, as well as after applying various processing, including absolute flux calibration, telluric removal, normalisation and barycentric correction; and (iii) co-added flux-calibrated and rectified spectra over the full optical range, for which all available XShootU exposures were combined. For many of the targets, the final signal-to-noise ratio per resolution element is above 200 in both the UVB and the VIS co-added spectra. The reduced data and advanced scientific data products will be made available to the community upon publication of this paper. [...], Comment: 22 pages, 19 figures; accepted for publication in Astronomy & Astrophysics. Links to online tables and databases will be included upon publication

We present the integrated VLT-MUSE spectrum of the central 2'x2' (30x30 pc$^{2}$) of NGC 2070, the dominant giant HII region of the Tarantula Nebula in the Large Magellanic Cloud, together withan empirical far-ultraviolet spectrum constructed via LMC template stars from the ULLYSES survey and Hubble Tarantula Treasury Project UV photometry. NGC 2070 provides a unique opportunity to compare results from individual stellar populations (e.g. VLT FLAMES Tarantula Survey) in a metal-poor starburst region to the integrated results from the population synthesis tools Starburst99, Charlot & Bruzual and BPASS. The metallicity of NGC 2070 inferred from standard nebular strong line calibrations is 0.4$\pm$0.1 dex lower than obtained from direct methods. The Halpha inferred age of 4.2 Myr from Starburst99 is close to the median age of OB stars within the region, although individual stars span a broad range of 1-7 Myr. The inferred stellar mass is close to that obtained for the rich star cluster R136 within NGC 2070, although this contributes only 21% to the integrated far-UV continuum. HeII 1640 emission is dominated by classical WR stars and main sequence WNh+Of/WN stars. 18% of the NGC~2070 far UV continuum flux arises from very massive stars with >100 Msun, including several very luminous Of supergiants. None of the predicted population synthesis models at low metallicities are able to successfully reproduce the far-UV spectrum of NGC 2070. We attribute issues to the treatment of mass-loss in very massive stars, the lack of contemporary empirical metal-poor templates, plus WR stars produced via binary evolution., Comment: 15 pages, 16 figures, plus Appendix. Revised submission to MNRAS following initial referee report, comments welcome!