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Organic semiconductors (OSCs) promise to deliver next‐generation electronic and energy devices that are flexible, scalable and printable. Unfortunately, realizing this opportunity is hampered by increasing concerns about the use of volatile organic compounds (VOCs), particularly toxic halogenated solvents that are detrimental to the environment and human health. Here, a cradle‐to‐grave process is reported to achieve high performance p‐ and n‐type OSC devices based on indacenodithiophene and diketopyrrolopyrrole semiconducting polymers that utilizes aqueous‐processes, fewer steps, lower reaction temperatures, a significant reduction in VOCs (>99%) and avoids all halogenated solvents. The process involves an aqueous mini‐emulsion polymerization that generates a surfactant‐stabilized aqueous dispersion of OSC nanoparticles at sufficient concentration to permit direct aqueous processing into thin films for use in organic field‐effect transistors. Promisingly, the performance of these devices is comparable to those prepared using conventional synthesis and processing procedures optimized for large amounts of VOCs and halogenated solvents. Ultimately, the holistic approach reported addresses the environmental issues and enables a viable guideline for the delivery of future OSC devices using only aqueous media for synthesis, purification and thin‐film processing. An environmentally benign cradle‐to‐grave process from synthesis‐to‐device is demonstrated for high performance organic field‐effect transistors. This holistic approach uses aqueous processes from mini‐emulsion polymerization to purification and thin‐film deposition. Compared to conventional approaches, the process requires fewer steps, lower reaction temperatures, a significant reduction in the use of volatile organic compounds and avoids toxic halogenated solvents.

An interdigitated electrode sensor was designed and microfabricated for measuring the changes in the capacitance of three phosphate selective molecularly imprinted polymer (MIP) formulations, in order to provide hydroponics users with a portable nutrient sensing tool. The MIPs investigated were synthesised using different combinations of the functional monomers methacrylic acid (MAA) and N-allylthiourea, against the template molecules diphenyl phosphate, triethyl phosphate, and trimethyl phosphate. A cross-interference study between phosphate, nitrate, and sulfate was carried out for the MIP materials using an inductance, capacitance, and resistance (LCR) meter. Capacitance measurements were taken by applying an alternating current (AC) with a potential difference of 1 V root mean square (RMS) at a frequency of 1 kHz. The cross-interference study demonstrated a strong binding preference to phosphate over the other nutrient salts tested for each formulation. The size of template molecule and length of the functional monomer side groups also determined that a short chain functional monomer in combination with a template containing large R-groups produced the optimal binding site conditions when synthesising a phosphate selective MIP.

Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample ( N  = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits’ PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder. The genetic underpinnings of alcohol use disorder and consumption are incompletely understood. Here, the authors perform GWAS for Alcohol Use Disorder (AUD) Identification Test-Consumption scores and AUD diagnosis from electronic health records of 274,424 individuals and identify a total of 18 associated loci.

AbstractObjectiveTo evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States.DesignObservational cohort study.SettingNationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system.ParticipantsAll 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation.Main outcome measuresThe main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion.ResultsOf 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses.ConclusionsEarly initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

Multi-beam scanning electron microscopy (mSEM) enables high-throughput, nano-resolution imaging of macroscopic tissue samples, providing an unprecedented means for structure-function characterization of biological tissues and their cellular inhabitants, seamlessly across multiple length scales. Here we describe computational methods to reconstruct and navigate a multitude of high-resolution mSEM images of the human hip. We calculated cross-correlation shift vectors between overlapping images and used a mass-spring-damper model for optimal global registration. We utilized the Google Maps API to create an interactive map and provide open access to our reconstructed mSEM datasets to both the public and scientific communities via our website www.mechbio.org. The nano- to macro-scale map reveals the tissue's biological and material constituents. Living inhabitants of the hip bone (e.g. osteocytes) are visible in their local extracellular matrix milieu (comprising collagen and mineral) and embedded in bone's structural tissue architecture, i.e. the osteonal structures in which layers of mineralized tissue are organized in lamellae around a central blood vessel. Multi-beam SEM and our presented methodology enable an unprecedented, comprehensive understanding of health and disease from the molecular to organ length scale.

The Global Fuel Exploitation Inventory (GFEI) is a global 0.1° x 0.1° resolution gridded inventory of methane emissions from oil, gas, and coal exploitation. Here, we present GFEI v3 with updated national emissions to 2020 using reports submitted to the United Nations Framework Convention on Climate Change (UNFCCC), leading to new global emissions of 23, 20, and 31 Tg a.sup.-1 for oil, gas, and coal, respectively. We also use new geospatial information from the Oil and Gas Infrastructure Mapping database (OGIM v1) for spatial distribution of global oil-gas methane emissions. We use coal mine locations from the Global Energy Monitor's Global Coal Mine Tracker (GCMT), combined with our own estimates for mine-level methane emissions, to distribute national emissions between coal mine locations. Our mine-level methane emission estimates use country specific emission factors for top producing countries supplemented with modeled emission factors based on coal mine depth and grade. We see the greatest change in the spatial distribution of emissions in GFEI v3 compared to v2 in China due to the use of GCMT for coal mine locations. Large point source plumes (super-emitters) observed by the NASA EMIT instrument are co-located with infrastructure identified in GFEI v3, but the magnitude of the measured emissions is poorly correlated with the gridded emissions in GFEI. This may reflect missing or misrepresented sources in GFEI v3 but also the sporadic nature of the super-emitter measurements used here. By aligning GFEI v3 with national UNFCCC reports and using state-of-the-science geospatial information, the inventory can be confronted with satellite observations of atmospheric methane through inverse modeling to evaluate and improve the UNFCCC reports. We plan to continue updating GFEI to align with reported national emissions and new geospatial information, including assessment of GFEI spatial accuracy through comparison to super-emitter detections. GFEI v3 emission grids by sector and subsector are available at

A complex conformational energy landscape determines G-protein-coupled receptor (GPCR) signalling via intracellular binding partners (IBPs), e.g., G s and β-arrestin. Using 13 C methyl methionine NMR for the β 1 -adrenergic receptor, we identify ligand efficacy-dependent equilibria between an inactive and pre-active state and, in complex with G s -mimetic nanobody, between more and less active ternary complexes. Formation of a basal activity complex through ligand-free nanobody–receptor interaction reveals structural differences on the cytoplasmic receptor side compared to the full agonist-bound nanobody-coupled form, suggesting that ligand-induced variations in G-protein interaction underpin partial agonism. Significant differences in receptor dynamics are observed ranging from rigid nanobody-coupled states to extensive μs-to-ms timescale dynamics when bound to a full agonist. We suggest that the mobility of the full agonist-bound form primes the GPCR to couple to IBPs. On formation of the ternary complex, ligand efficacy determines the quality of the interaction between the rigidified receptor and an IBP and consequently the signalling level. β 1 -adrenergic receptors are expressed in cardiac tissue and stimulated by the sympathetic nervous system. Here, the authors use NMR spectroscopy to unravel the conformational diversity upon β 1 -adrenergic receptor activation and provide structural insights into partial agonism and basal activity.

SPI1 was recently reported as a genetic risk factor for Alzheimer’s disease (AD) in large-scale genome-wide association studies. However, it is unknown whether SPI1 should be downregulated or increased to have therapeutic benefits. To investigate the effect of modulating SPI1 levels on AD pathogenesis, we performed extensive biochemical, histological, and transcriptomic analyses using both Spi1 -knockdown and Spi1 -overexpression mouse models. Here, we show that the knockdown of Spi1 expression significantly exacerbates insoluble amyloid-β (Aβ) levels, amyloid plaque deposition, and gliosis. Conversely, overexpression of Spi1 significantly ameliorates these phenotypes and dystrophic neurites. Further mechanistic studies using targeted and single-cell transcriptomics approaches demonstrate that altered Spi1 expression modulates several pathways, such as immune response pathways and complement system. Our data suggest that transcriptional reprogramming by targeting transcription factors, like Spi1 , might hold promise as a therapeutic strategy. This approach could potentially expand the current landscape of druggable targets for AD. Although SPI1 gene was identified as a risk factor for Alzheimer’s disease, its role in the disease remains unclear. Here, the authors show that decreasing SPI1 level exacerbates disease symptoms, whereas increasing its level ameliorates phenotypes.

A majority of children admitted to a single hospital in late 2021–early 2022 with acute hepatitis of unknown cause tested positive for adenovirus. This report describes the children’s illnesses and outcomes.

Substantial progress has been made in understanding the involvement of malondialdehyde-acetaldehyde (MAA) adducts in rheumatoid arthritis (RA) pathogenesis. This systematic review synthesizes current evidence on the role of MAA-modified macromolecules and anti-MAA antibodies in the development, manifestation, and progression of RA. MEDLINE, EMBASE, the Cochrane Library, Scopus, and SciFinder were searched through May 6, 2025. Studies were screened based on predefined inclusion/exclusion criteria. Study characteristics were extracted, and quality assessments were performed. MAA-modified proteins and MAA-specific autoreactive B cells are elevated in synovial and lung tissues of RA patients. Anti-MAA antibodies are enriched in RA-derived synovial fluids compared to serum. Serum levels of anti-MAA IgG and IgA are increased prior to RA onset, and though not RA-specific, were higher in RA patients than those with other conditions. Anti-MAA antibodies do not cross-react with other autoantibodies, such as anti-citrullinated protein autoantibodies, and can be detected in sera from seronegative RA patients. Elevated anti-MAA antibody levels correlate with progression of joint, lung, and cardiovascular complications, as well as biologic treatment responses. Human and animal studies have begun to elucidate mechanisms by which MAA and anti-MAA antibody might contribute to inflammatory and fibrotic changes in RA. This review provides a comprehensive overview of MAA and its involvement in RA pathogenesis. MAA adducts contribute to loss of immune tolerance and promote both inflammation and fibrosis in RA. Given associations of anti-MAA antibodies with RA disease activity and complications, MAA-related pathways hold promise as both biomarkers and treatment targets in RA. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD4202454490.