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Anemia is associated with worse outcome in stroke, but the impact of anemia with intravenous thrombolysis or endovascular therapy has hardly been delineated. The aim of this study was to analyze the role of anemia on infarct evolution and outcome after acute stroke treatment. 1158 patients from Bern and 321 from Los Angeles were included. Baseline data and 3 months outcome assessed with the modified Rankin Scale were recorded prospectively. Baseline DWI lesion volumes were measured in 345 patients and both baseline and final infarct volumes in 180 patients using CT or MRI. Multivariable and linear regression analysis were used to determine predictors of outcome and infarct growth. 712 patients underwent endovascular treatment and 446 intravenous thrombolysis. Lower hemoglobin at baseline, at 24h, and nadir until day 5 predicted poor outcome (OR 1.150-1.279) and higher mortality (OR 1.131-1.237) independently of treatment. Decrease of hemoglobin after hospital arrival, mainly induced by hemodilution, predicted poor outcome and had a linear association with final infarct volumes and the amount and velocity of infarct growth. Infarcts of patients with newly observed anemia were twice as large as infarcts with normal hemoglobin levels. Anemia at hospital admission and any hemoglobin decrease during acute stroke treatment affect outcome negatively, probably by enlarging and accelerating infarct growth. Our results indicate that hemodilution has an adverse effect on penumbral evolution. Whether hemoglobin decrease in acute stroke could be avoided and whether this would improve outcome would need to be studied prospectively.

The evolution of organic aerosol (OA) and brown carbon (BrC) in wildfire plumes, including the relative contributions of primary versus secondary sources, has been uncertain in part because of limited knowledge of the precursor emissions and the chemical environment of smoke plumes. We made airborne measurements of a suite of reactive trace gases, particle composition, and optical properties in fresh western US wildfire smoke in July through August 2018. We use these observations to quantify primary versus secondary sources of biomass-burning OA (BBPOA versus BBSOA) and BrC in wildfire plumes. When a daytime wildfire plume dilutes by a factor of 5 to 10, we estimate that up to one-third of the primary OA has evaporated and subsequently reacted to form BBSOA with near unit yield. The reactions of measured BBSOA precursors contribute only 13 ± 3% of the total BBSOA source, with evaporated BBPOA comprising the rest. We find that oxidation of phenolic compounds contributes the majority of BBSOA from emitted vapors. The corresponding particulate nitrophenolic compounds are estimated to explain 29 ± 15% of average BrC light absorption at 405 nm (BrC Abs405) measured in the first few hours of plume evolution, despite accounting for just 4 ± 2% of average OA mass. These measurements provide quantitative constraints on the role of dilution-driven evaporation of OA and subsequent radical-driven oxidation on the fate of biomass-burning OA and BrC in daytime wildfire plumes and point to the need to understand how processing of nighttime emissions differs.

We present an 870 μm continuum survey of 300 protostars from the Herschel Orion Protostar Survey using the Atacama Compact Array (ACA). These data measure protostellar flux densities on envelope scales ≤8000 au (20″) and resolve the structure of envelopes with 1600 au (4″) resolution, a factor of 3–5 improvement in angular resolution over existing single-dish 870 μm observations. We compare the ACA observations to Atacama Large Millimeter/submillimeter Array 12 m array observations at 870 μm with ∼0.″1 (40 au) resolution. Using the 12 m data to measure the fluxes from disks and the ACA data within 2500 au to measure the combined disk plus envelope fluxes, we calculate the 12 m/ACA 870 μm flux ratios. Our sample shows a clear evolution in this ratio. Class 0 protostars are mostly envelope-dominated with ratios <0.5. In contrast, Flat Spectrum protostars are primarily disk-dominated with ratios near 1, although with a number of face-on protostars dominated by their envelopes. Class I protostars span the range from envelope to disk-dominated. The increase in ratio is accompanied by a decrease in the envelope fluxes and estimated mass infall rates. We estimate that 80% of the mass is accreted during the envelope-dominated phase. We find that the 12 m/ACA flux ratio is an evolutionary indicator that largely avoids the inclination and foreground extinction dependence of spectral energy distribution-based indicators.

Measured spectral shifts due to intrinsic stellar variability (e.g., pulsations, granulation) and activity (e.g., spots, plages) are the largest source of error for extreme-precision radial-velocity (EPRV) exoplanet detection. Several methods are designed to disentangle stellar signals from true center-of-mass shifts due to planets. The Extreme-precision Spectrograph (EXPRES) Stellar Signals Project (ESSP) presents a self-consistent comparison of 22 different methods tested on the same extreme-precision spectroscopic data from EXPRES. Methods derived new activity indicators, constructed models for mapping an indicator to the needed radial-velocity (RV) correction, or separated out shape- and shift-driven RV components. Since no ground truth is known when using real data, relative method performance is assessed using the total and nightly scatter of returned RVs and agreement between the results of different methods. Nearly all submitted methods return a lower RV rms than classic linear decorrelation, but no method is yet consistently reducing the RV rms to sub-meter-per-second levels. There is a concerning lack of agreement between the RVs returned by different methods. These results suggest that continued progress in this field necessitates increased interpretability of methods, high-cadence data to capture stellar signals at all timescales, and continued tests like the ESSP using consistent data sets with more advanced metrics for method performance. Future comparisons should make use of various well-characterized data sets—such as solar data or data with known injected planetary and/or stellar signals—to better understand method performance and whether planetary signals are preserved.

Disorders of consciousness are characterized by severe impairments in arousal and awareness. Deep brain stimulation is a potential treatment, but outcomes vary—possibly due to differences in patient characteristics, electrode placement, or the specific brain network engaged. We describe 40 patients with disorders of consciousness undergoing deep brain stimulation targeting the thalamic centromedian-parafascicular complex. Improvements in consciousness are associated with better-preserved gray matter, particularly in the striatum. Electric field modeling reveals that stimulation is most effective when it extends below the centromedian nucleus, engaging the inferior parafascicular nucleus and the adjacent ventral tegmental tract—a pathway that connects the brainstem and hypothalamus and runs along the midbrain-thalamus border. External validation analyses show that effective stimulation engages a brain network overlapping with disrupted patterns of brain activity observed in two independent cohorts with impaired consciousness: one with arousal-impairing stroke lesions and the other with awareness-impairing seizures. Together, these findings advance the field by informing patient selection, refining stimulation targets, and identifying a brain network linked to recovery that may have broader therapeutic relevance across consciousness-impairing conditions. In people with severe brain injuries, stimulation restored consciousness by engaging a deep brain circuit for wakefulness—revealing a target that may also guide treatment in stroke and epilepsy.

Persons with lymphatic filariasis (LF) are often co-infected with soil-transmitted helminths. A single co-administered dose of ivermectin/diethylcarbamazine/albendazole (IDA) is recommended by WHO for mass drug administration (MDA) for LF instead of diethylcarbamazine/albendazole (DA) in Papua New Guinea (PNG). We compared the effectiveness of a single round of MDA with IDA or DA on hookworm and strongyloidiasis in PNG. This study was conducted as part of a cluster randomized trial of MDA with IDA versus DA for LF in individuals willing to provide stool and blood samples at baseline and 12 months after MDA. Participants from 23 villages were included in the clinical trial. Primary outcomes were changes in hookworm prevalence and infection intensity assessed by Kato Katz and Strongyloides prevalence by serology. Hookworm prevalence at baseline was 78% (91/117) and 80% (119/149) in villages assigned to DA and IDA treatment, respectively. Twelve months post-MDA, hookworm prevalence decreased to 56.5% in DA- and 34.4% in IDA-treated villages, respectively (p<0.001, both comparisons). The proportion of individuals with moderate to heavy infection (>2000 egg per gram (EPG)) similarly decreased from 8.7% to 1.5% after DA (p = 0.001) and from 5.7% to 1.0% after IDA (p = 0.002). Using a logistic regression model adjusting for age, gender, baseline hookworm prevalence, and village drug coverage, IDA resulted in a 45% greater reduction in hookworm prevalence than DA (Odds ratio 0.55, 95% CI [0.31,0.99], p = 0.049). MDA also reduced hookworm transmission. Strongyloides seroprevalence at baseline was 68% (192/283) and 62% (180/290) in IDA and DA villages, respectively, with 49% becoming seronegative in the IDA versus 23% in DA villages at 12 months (p = 0.0001). MDA with IDA was more effective than DA for reducing hookworm and Strongyloides infections in PNG, extending the benefit of MDA with IDA beyond its effect on LF.

Genomic alterations shape cell phenotypes and the structure of tumor ecosystems in poorly defined ways. To investigate these relationships, we used imaging mass cytometry to quantify the expression of 37 proteins with subcellular spatial resolution in 483 tumors from the METABRIC cohort. Single-cell analysis revealed cell phenotypes spanning epithelial, stromal and immune types. Distinct combinations of cell phenotypes and cell-cell interactions were associated with genomic subtypes of breast cancer. Epithelial luminal cell phenotypes separated into those predominantly impacted by mutations and those affected by copy number aberrations. Several features of tumor ecosystems, including cellular neighborhoods, were linked to prognosis, illustrating their clinical relevance. In summary, systematic analysis of single-cell phenotypic and spatial correlates of genomic alterations in cancer revealed how genomes shape both the composition and architecture of breast tumor ecosystems and will enable greater understanding of the phenotypic impact of genomic alterations.

Protein sequences preserved in two Quaternary taxa, Macrauchenia and Toxodon , resolve the evolutionary history of South American native ungulates. South American ungulates demystified When Charles Darwin first unearthed the remains of the South American native ungulates — herbivorous mammals that evolved in isolation on the South American continent for tens of millions of years — he declared them “the strangest animals ever discovered”. Their origins are obscured by rampant convergence of morphology, and work with ancient DNA has been similarly frustrating. Ian Barnes and colleagues have circumvented these problems by screening protein sequences preserved in two Quaternary taxa, Macrauchenia and Toxodon , to show that their closest relatives among other mammals are the Perissodactyls (odd-toed ungulates such as horses and rhinos) rather than among the Afrotheres (elephants, sirenians and allies). No large group of recently extinct placental mammals remains as evolutionarily cryptic as the approximately 280 genera grouped as ‘South American native ungulates’. To Charles Darwin 1 , 2 , who first collected their remains, they included perhaps the ‘strangest animal[s] ever discovered’. Today, much like 180 years ago, it is no clearer whether they had one origin or several, arose before or after the Cretaceous/Palaeogene transition 66.2 million years ago 3 , or are more likely to belong with the elephants and sirenians of superorder Afrotheria than with the euungulates (cattle, horses, and allies) of superorder Laurasiatheria 4 , 5 , 6 . Morphology-based analyses have proved unconvincing because convergences are pervasive among unrelated ungulate-like placentals. Approaches using ancient DNA have also been unsuccessful, probably because of rapid DNA degradation in semitropical and temperate deposits. Here we apply proteomic analysis to screen bone samples of the Late Quaternary South American native ungulate taxa Toxodon (Notoungulata) and Macrauchenia (Litopterna) for phylogenetically informative protein sequences. For each ungulate, we obtain approximately 90% direct sequence coverage of type I collagen α1- and α2-chains, representing approximately 900 of 1,140 amino-acid residues for each subunit. A phylogeny is estimated from an alignment of these fossil sequences with collagen (I) gene transcripts from available mammalian genomes or mass spectrometrically derived sequence data obtained for this study. The resulting consensus tree agrees well with recent higher-level mammalian phylogenies 7 , 8 , 9 . Toxodon and Macrauchenia form a monophyletic group whose sister taxon is not Afrotheria or any of its constituent clades as recently claimed 5 , 6 , but instead crown Perissodactyla (horses, tapirs, and rhinoceroses). These results are consistent with the origin of at least some South American native ungulates 4 , 6 from ‘condylarths’, a paraphyletic assembly of archaic placentals. With ongoing improvements in instrumentation and analytical procedures, proteomics may produce a revolution in systematics such as that achieved by genomics, but with the possibility of reaching much further back in time.

Desert varnish is a dark rock coating that forms in arid environments worldwide. It is highly and selectively enriched in manganese, the mechanism for which has been a long-standing geological mystery. We collected varnish samples from diverse sites across the western United States, examined them in petrographic thin section using microscale chemical imaging techniques, and investigated the associated microbial communities using 16S amplicon and shotgun metagenomic DNA sequencing. Our analyses described a material governed by sunlight, water, and manganese redox cycling that hosts an unusually aerobic microbial ecosystem characterized by a remarkable abundance of photosynthetic Cyanobacteria in the genus Chroococcidiopsis as the major autotrophic constituent. We then showed that diverse Cyanobacteria, including the relevant Chroococcidiopsis taxon, accumulate extraordinary amounts of intracellular manganese—over two orders of magnitude higher manganese content than other cells. The speciation of this manganese determined by advanced paramagnetic resonance techniques suggested that the Cyanobacteria use it as a catalytic antioxidant—a valuable adaptation for coping with the substantial oxidative stress present in this environment. Taken together, these results indicated that the manganese enrichment in varnish is related to its specific uptake and use by likely founding members of varnish microbial communities.