A comprehensive dataset of annotated brain metastasis MR images with clinical and radiomic data.

Brain metastasis (BM) is one of the main complications of many cancers, and the most frequent malignancy of the central nervous system. Imaging studies of BMs are routinely used for diagnosis of disease, treatment planning and follow-up. Artificial Intelligence (AI) has great potential to provide automated tools to assist in the management of disease. However, AI methods require large datasets for training and validation, and to date there have been just one publicly available imaging dataset of 156 BMs. This paper publishes 637 high-resolution imaging studies of 75 patients harboring 260 BM lesions, and their respective clinical data. It also includes semi-automatic segmentations of 593 BMs, including pre- and post-treatment T1-weighted cases, and a set of morphological and radiomic features for the cases segmented. This data-sharing initiative is expected to enable research into and performance evaluation of automatic BM detection, lesion segmentation, disease status evaluation and treatment planning methods for BMs, as well as the development and validation of predictive and prognostic tools with clinical applicability

Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1

Genetic Alzheimer’s disease (AD) risk factors associate with reduced defensive amyloid β plaque-associated microglia (AβAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe con- comitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AβAM clustering and proliferation and increases Aβ neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aβ plaque microglial coverage and an increase of Aβ plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction

Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1

Genetic Alzheimer’s disease (AD) risk factors associate with reduced defensive amyloid β plaque-associated microglia (AβAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AβAM clustering and proliferation and increases Aβ neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aβ plaque microglial coverage and an increase of Aβ plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction.R.M.-D. was the recipient of a Sara Borrell fellowship from Instituto de Salud Carlos III (ISCIII) (CD09/0007). N.L.-U., C.O.-d.S.L., C.R.-M. and M.I.A.-V. were the recipients of FPU fellowships from Spanish Ministry of Education, Culture and Sport (FPU14/02115, AP2010‐1598, FPU16/02050 and FPU15/02898, respectively). A.H.-G. was the recipient of an FPI fellowship from the Spanish Ministry of Education, Culture and Sport (BES-2010-033886). This work was supported by grants from the Spanish MINEICO, ISCIII and FEDER (European Union) (SAF2012‐33816, SAF2015‐64111‐R, SAF2017-90794-REDT and PIE13/0004 to A.P.); by the Regional Government of Andalusia co-funded by CEC and FEDER funds (European Union) (‘Proyectos de Excelencia’; P12‐CTS‐2138 and P12‐CTS‐2232 to A.P.); by the ‘Ayuda de Biomedicina 2018’, Fundación Domingo Martínez (to A.P.) ; by the ISCIII of Spain, co-financed by FEDER funds (European Union) through grants PI18/01556 (to J.V.) and PI18/01557 (to A. Gutierrez); by Junta de Andalucía, co-financed by FEDER funds (grants UMA18-FEDERJA-211 (to A. Gutierrez) and US‐1262734 (to J.V.)); and by Spanish MINEICO (BFU2016-76872-R and BES-2011-047721 to E.B.).Peer reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

First Sagittarius A* Event Horizon Telescope Results. IV. Variability, Morphology, and Black Hole Mass

In this paper we quantify the temporal variability and image morphology of the horizon-scale emission from Sgr A*, as observed by the EHT in 2017 April at a wavelength of 1.3 mm. We find that the Sgr A* data exhibit variability that exceeds what can be explained by the uncertainties in the data or by the effects of interstellar scattering. The magnitude of this variability can be a substantial fraction of the correlated flux density, reaching ∼100% on some baselines. Through an exploration of simple geometric source models, we demonstrate that ring-like morphologies provide better fits to the Sgr A* data than do other morphologies with comparable complexity. We develop two strategies for fitting static geometric ring models to the time-variable Sgr A* data; one strategy fits models to short segments of data over which the source is static and averages these independent fits, while the other fits models to the full data set using a parametric model for the structural variability power spectrum around the average source structure. Both geometric modeling and image-domain feature extraction techniques determine the ring diameter to be 51.8 ± 2.3 μas (68% credible intervals), with the ring thickness constrained to have an FWHM between ∼30% and 50% of the ring diameter. To bring the diameter measurements to a common physical scale, we calibrate them using synthetic data generated from GRMHD simulations. This calibration constrains the angular size of the gravitational radius to be 4.8−0.7+1.4 μas, which we combine with an independent distance measurement from maser parallaxes to determine the mass of Sgr A* to be 4.0−0.6+1.1×106 M ⊙

The Event Horizon Telescope Image of the Quasar NRAO 530

We report on the observations of the quasar NRAO 530 with the Event Horizon Telescope (EHT) on 2017 April 5−7, when NRAO 530 was used as a calibrator for the EHT observations of Sagittarius A*. At z = 0.902, this is the most distant object imaged by the EHT so far. We reconstruct the first images of the source at 230 GHz, at an unprecedented angular resolution of ∼20 μas, both in total intensity and in linear polarization (LP). We do not detect source variability, allowing us to represent the whole data set with static images. The images reveal a bright feature located on the southern end of the jet, which we associate with the core. The feature is linearly polarized, with a fractional polarization of ∼5%–8%, and it has a substructure consisting of two components. Their observed brightness temperature suggests that the energy density of the jet is dominated by the magnetic field. The jet extends over 60 μas along a position angle ∼ −28°. It includes two features with orthogonal directions of polarization (electric vector position angle), parallel and perpendicular to the jet axis, consistent with a helical structure of the magnetic field in the jet. The outermost feature has a particularly high degree of LP, suggestive of a nearly uniform magnetic field. Future EHT observations will probe the variability of the jet structure on microarcsecond scales, while simultaneous multiwavelength monitoring will provide insight into the high-energy emission origin

First Sagittarius A* Event Horizon Telescope Results. VI. Testing the Black Hole Metric

Astrophysical black holes are expected to be described by the Kerr metric. This is the only stationary, vacuum, axisymmetric metric, without electromagnetic charge, that satisfies Einstein’s equations and does not have pathologies outside of the event horizon. We present new constraints on potential deviations from the Kerr prediction based on 2017 EHT observations of Sagittarius A* (Sgr A*). We calibrate the relationship between the geometrically defined black hole shadow and the observed size of the ring-like images using a library that includes both Kerr and non-Kerr simulations. We use the exquisite prior constraints on the mass-to-distance ratio for Sgr A* to show that the observed image size is within ∼10% of the Kerr predictions. We use these bounds to constrain metrics that are parametrically different from Kerr, as well as the charges of several known spacetimes. To consider alternatives to the presence of an event horizon, we explore the possibility that Sgr A* is a compact object with a surface that either absorbs and thermally reemits incident radiation or partially reflects it. Using the observed image size and the broadband spectrum of Sgr A*, we conclude that a thermal surface can be ruled out and a fully reflective one is unlikely. We compare our results to the broader landscape of gravitational tests. Together with the bounds found for stellar-mass black holes and the M87 black hole, our observations provide further support that the external spacetimes of all black holes are described by the Kerr metric, independent of their mass

Characterizing and Mitigating Intraday Variability: Reconstructing Source Structure in Accreting Black Holes with mm-VLBI

The extraordinary physical resolution afforded by the Event Horizon Telescope has opened a window onto the astrophysical phenomena unfolding on horizon scales in two known black holes, M87* and Sgr A*. However, with this leap in resolution has come a new set of practical complications. Sgr A* exhibits intraday variability that violates the assumptions underlying Earth aperture synthesis, limiting traditional image reconstruction methods to short timescales and data sets with very sparse (u, v) coverage. We present a new set of tools to detect and mitigate this variability. We develop a data-driven, model-agnostic procedure to detect and characterize the spatial structure of intraday variability. This method is calibrated against a large set of mock data sets, producing an empirical estimator of the spatial power spectrum of the brightness fluctuations. We present a novel Bayesian noise modeling algorithm that simultaneously reconstructs an average image and statistical measure of the fluctuations about it using a parameterized form for the excess variance in the complex visibilities not otherwise explained by the statistical errors. These methods are validated using a variety of simulated data, including general relativistic magnetohydrodynamic simulations appropriate for Sgr A* and M87*. We find that the reconstructed source structure and variability are robust to changes in the underlying image model. We apply these methods to the 2017 EHT observations of M87*, finding evidence for variability across the EHT observing campaign. The variability mitigation strategies presented are widely applicable to very long baseline interferometry observations of variable sources generally, for which they provide a data-informed averaging procedure and natural characterization of inter-epoch image consistency