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Abstract Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance.

During swimming, many fishes use pectoral fins for propulsion and, in the process, move substantial amounts of water rearward. However, the effect that this upstream wake has on the caudal fin remains largely unexplored. By coordinating motions of the caudal fin with the pectoral fins, fishes have the potential to create constructive flow interactions which may act to partially recapture the upstream energy lost in the pectoral fin wake. Using experimentally derived velocity and pressure fields for the silver mojarra (Eucinostomus argenteus), we show that pectoral–caudal fin (PCF) coordination enables the circulation and interception of pectoral fin wake vortices by the caudal fin. This acts to transfer energy to the caudal fin and enhance its hydrodynamic efficiency at swimming speeds where this behaviour occurs. We also find that mojarras commonly use PCF coordination in nature. The results offer new insights into the evolutionary drivers and behavioural plasticity of fish swimming as well as for developing more capable bioinspired underwater vehicles.

Summary: Background: Steroidogenic factor 1 (SF-1/NR5A1) is essential for human sex development. Heterozygous NR5A1/SF-1 variants manifest with a broad range of phenotypes of differences of sex development (DSD), which remain unexplained. Methods: We conducted a retrospective analysis on the so far largest international cohort of individuals with NR5A1/SF-1 variants, identified through the I-DSD registry and a research network. Findings: Among 197 individuals with NR5A1/SF-1 variants, we confirmed diverse phenotypes. Over 70% of 46, XY individuals had a severe DSD phenotype, while 90% of 46, XX individuals had female-typical sex development. Close to 100 different novel and known NR5A1/SF-1 variants were identified, without specific hot spots. Additionally, likely disease-associated variants in other genes were reported in 32 individuals out of 128 tested (25%), particularly in those with severe or opposite sex DSD phenotypes. Interestingly, 48% of these variants were found in known DSD or SF-1 interacting genes, but no frequent gene-clusters were identified. Sex registration at birth varied, with

Abstract Mapped representations of species−habitat relationships often underlie approaches to prioritize area‐based conservation strategies to meet conservation goals for biodiversity. Generally a single surrogate species is used to inform conservation design, with the assumption that conservation actions for an appropriately selected species will confer benefits to a broader community of organisms. Emerging conservation frameworks across western North America are now relying on derived measures of intactness from remotely sensed vegetation data, wholly independent from species data. Understanding the efficacy of species‐agnostic planning approaches is a critical step to ensuring the robustness of emerging conservation designs. We developed an approach to quantify ‘strength of surrogacy’, by applying prioritization algorithms to previously developed species models, and measuring their coverage provided to a broader wildlife community. We used this inference to test the relative surrogacy among a suite of species models used for conservation targeting in the endangered grasslands of the Northern Sagebrush Steppe, where careful planning can help stem the loss of private grazing lands to cultivation. In this test, we also derived a simpler surrogate of intact rangelands without species data for conservation targeting, along with a measure of combined migration representative of key areas for connectivity. Our measure of intactness vastly outperformed any species model as a surrogate for conservation, followed by that of combined migration, highlighting the efficacy of strategies that target large and intact rangeland cores for wildlife conservation and restoration efforts.

Se dilucida el sfatus sistemát¡co de var¡os ejemplares pertenecientes a la familia CHIIVIAERIDAE colectados durante las campañas de pesca exploratoria realizadas en 1995 a bordo del B/P Orense, en las aguas de la Zona Económica Exclusiva (ZEE) del Pacíflco de América Central. La literatura revisada, permite citar a los individuos como Chimaera sp C y los mismos representarÍan un nuevo reg¡stro para la fauna de peces batipelágicos en la región estudiada. Los valores promedio de la longitud total y peso decrecen de Panamá hacia Guatemala. Se calcularon las curvas de regresión para la relación Longitud total/peso para las muestras de cada país.

AbstractCassia tora Linn. is a medicinal herb that has traditionally been used to prevent diseases. The study investigated the changes in bioactive compounds of Cassia tora seeds during 3-days of germination. The seeds were thoroughly cleaned, soaked in deionized water at 20 °C for 2 h, and germinated at 25 °C and 90% relative humidity in a seed germinator. Germinating C. tora seeds were picked up at 24 h intermissions over 3-day germination duration. The germinating C. tora was freeze-dried and pulverized through a 1 mm mesh screen. During the germination process, the crude ash, crude fat, and crude protein content of C. tora seeds increased slightly. The main carotenoid compounds identified in this study were lutein and β-carotenes, and the total carotenoid content increased up to 4.35 µg/g after 72-hours of germination, which was 1.73-times higher compared to that in raw C. tora seeds. The anthocyanin and vitamin C content also increased during the germination period, being 1.44-times and 1.72-times, respectively, higher after 72-hours of germination than that in the raw C. tora seeds. In addition, phenolics and flavonoids in C. tora seeds had a tendency to increase after germination, subsequently increasing in vitro antioxidant activities (ABTS and DPPH-radical scavenging activities). Proper germination of C. tora might be a convenient and efficient method to increase antioxidant bioactive compounds in our diet to exploit the related health benefits.

The Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). A key feature of CCv.4.0 is the more rigorous and expansive protocol that incorporates single wet swallows acquired in different positions (supine, upright) and provocative testing, including multiple rapid swallows and rapid drink challenge. Additionally, solid bolus swallows, solid test meal, and/or pharmacologic provocation can be used to identify clinically relevant motility disorders and other conditions (eg, rumination) that occur during and after meals. The acquisition and analysis for performing these tests and the evidence supporting their inclusion in the Chicago Classification protocol is detailed in this technical review. Provocative tests are designed to increase the diagnostic sensitivity and specificity of HRM studies for disorders of esophageal motility. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification, decrease the proportion of HRM studies that deliver inconclusive diagnoses and increase the number of patients with a clinically relevant diagnosis that can direct effective therapy. Another aim in establishing a standard manometry protocol for motility laboratories around the world is to facilitate procedural consistency, improve diagnostic reliability, and promote collaborative research.

Abstract Metabarcoding (high‐throughput sequencing of marker gene amplicons) has emerged as a promising and cost‐effective method for characterizing insect community samples. Yet, the methodology varies greatly among studies and its performance has not been systematically evaluated to date. In particular, it is unclear how accurately metabarcoding can resolve species communities in terms of presence‐absence, abundance and biomass. Here we use mock community experiments and a simple probabilistic model to evaluate the effect of different DNA extraction protocols on metabarcoding performance. Specifically, we ask four questions: (Q1) How consistent are the recovered community profiles across replicate mock communities?; (Q2) How does the choice of lysis buffer affect the recovery of the original community?; (Q3) How are community estimates affected by differing lysis times and homogenization? and (Q4) Is it possible to obtain adequate species abundance estimates through the use of biological spike‐ins? We show that estimates are quite variable across community replicates. In general, a mild lysis protocol is better at reconstructing species lists and approximate counts, while homogenization is better at retrieving biomass composition. Small insects are more likely to be detected in lysates, while some tough species require homogenization to be detected. Results are less consistent across biological replicates for lysates than for homogenates. Some species are associated with strong PCR amplification bias, which complicates the reconstruction of species counts. Yet, with adequate spike‐in data, species abundance can be determined with roughly 40% standard error for homogenates, and with roughly 50% standard error for lysates, under ideal conditions. In the latter case, however, this often requires species‐specific reference data, while spike‐in data generalize better across species for homogenates. We conclude that a non‐destructive, mild lysis approach shows the highest promise for the presence/absence description of the community, while also allowing future morphological or molecular work on the material. However, homogenization protocols perform better for characterizing community composition, in particular in terms of biomass.

Non-fullerene acceptors with large quadrupole moments strongly affect thin-film energetics. Here, the authors show a significant energetic shift (>200 meV) of Y6 upon changing its orientation from face-on to more edge-on using different solvents and its critical impact on organic photovoltaics.

Airborne imaging differential optical absorption spectroscopy (DOAS), ground-based stationary DOAS, and car DOAS measurements were conducted during the S5P-VAL-DE-Ruhr campaign in September 2020. The campaign area is located in the Rhine-Ruhr region of North Rhine-Westphalia, western Germany, which is a pollution hotspot in Europe comprising urban and large industrial sources. The DOAS measurements are used to validate spaceborne NO2 tropospheric vertical column density (VCD) data products from the Sentinel-5 Precursor (S5P) TROPOspheric Monitoring Instrument (TROPOMI). Seven flights were performed with the airborne imaging DOAS instrument for measurements of atmospheric pollution (AirMAP), providing measurements that were used to create continuous maps of NO2 in the layer below the aircraft. These flights cover many S5P ground pixels within an area of 30 km × 35 km and were accompanied by ground-based stationary measurements and three mobile car DOAS instruments. Stationary measurements were conducted by two Pandora, two Zenith-DOAS, and two MAX-DOAS instruments. Ground-based stationary and car DOAS measurements are used to evaluate the AirMAP tropospheric NO2 VCDs and show high Pearson correlation coefficients of 0.88 and 0.89 and slopes of 0.90 ± 0.09 and 0.89 ± 0.02 for the stationary and car DOAS, respectively. Having a spatial resolution of about 100 m × 30 m, the AirMAP tropospheric NO2 VCD data create a link between the ground-based and the TROPOMI measurements with a nadir resolution of 3.5 km × 5.5 km and are therefore well suited to validate the TROPOMI tropospheric NO2 VCD. The observations on the 7 flight days show strong NO2 variability, which is dependent on the three target areas, the day of the week, and the meteorological conditions. The AirMAP campaign data set is compared to the TROPOMI NO2 operational offline (OFFL) V01.03.02 data product, the reprocessed NO2 data using the V02.03.01 of the official level-2 processor provided by the Product Algorithm Laboratory (PAL), and several scientific TROPOMI NO2 data products. The AirMAP and TROPOMI OFFL V01.03.02 data are highly correlated (r=0.87) but show an underestimation of the TROPOMI data with a slope of 0.38 ± 0.02 and a median relative difference of −9 %. With the modifications in the NO2 retrieval implemented in the PAL V02.03.01 product, the slope and median relative difference increased to 0.83 ± 0.06 and +20 %. However, the modifications resulted in larger scatter and the correlation decreased significantly to r=0.72. The results can be improved by not applying a cloud correction for the TROPOMI data in conditions with high aerosol load and when cloud pressures are retrieved close to the surface. The influence of spatially more highly resolved a priori NO2 vertical profiles and surface reflectivity are investigated using scientific TROPOMI tropospheric NO2 VCD data products. The comparison of the AirMAP campaign data set to the scientific data products shows that the choice of surface reflectivity database has a minor impact on the tropospheric NO2 VCD retrieval in the campaign region and season. In comparison, the replacement of the a priori NO2 profile in combination with the improvements in the retrieval of the PAL V02.03.01 product regarding cloud heights can further increase the tropospheric NO2 VCDs. This study demonstrates that the underestimation of the TROPOMI tropospheric NO2 VCD product with respect to the validation data set has been and can be further significantly improved.

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.

Objectives: The aims of this study were: (a) to evaluate the performance of an artificial intelligence (AI) software package (Boneview Trauma, Gleamer) for the detection of post-traumatic bone fractures in radiography as a standalone; (b) used by two radiologists (osteoarticular senior and junior); and (c) to determine to whom AI would be most helpful. Materials and Methods: Within 14 days of a trauma, 101 consecutive patients underwent radiographic examination of the upper or lower limbs. The definite diagnosis for identifying fractures was: (a) radio-clinical consensus between the radiologist on-call who analyzed the images and the orthopedist (Group 1); (b) Cone Beam computed tomography (CBCT) exploration of the area of interest, in case of doubts or absence of consensus (Group 2). Independently of this diagnosis for both groups, the radiographic images were separately analyzed by two radiologists (osteoarticular senior: SR; junior: JR) prior without, and thereafter with the results of AI. Results: AI performed better than the radiologists in detecting common fractures (Group 1), but not subtle fractures (Group 2). In association with AI, both radiologists increased their overall performances in both groups, whereas this increase was significantly higher for the JR (p < 0.05). Conclusion: AI is reliable for common radiographic fracture identification and is a useful learning tool for radiologists in training. However, the software’s overall performance does not exceed that of an osteoarticular senior radiologist, particularly in case of subtle lesions.

Introduction Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal Salmonellae serovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containing S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.Method and analysis The Salmonella Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of S. Typhimurium and S. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.Ethics and dissemination Ethical approval for this study has been obtained from the South Central—Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.Trial registration number EudraCT Number: 2020-000510-14.

BackgroundHypertension is a major contributor to various adverse health outcomes. Although previous studies have shown the benefits of home blood pressure (BP) monitoring over office-based measurements, there is limited evidence comparing the effectiveness of whether a BP monitor integrated into the electronic health record is superior to a nonintegrated BP monitor. ObjectiveIn this paper, we describe the protocol for a pragmatic multisite implementation of a quality improvement initiative directly comparing integrated to nonintegrated BP monitors for hypertension improvement. MethodsWe will conduct a randomized, comparative effectiveness trial at 3 large academic health centers across California. The 3 sites will enroll a total of 660 participants (approximately n=220 per site), with 330 in the integrated BP monitor arm and 330 in the nonintegrated BP control arm. The primary outcome of this study will be the absolute difference in systolic BP in mm Hg from enrollment to 6 months. Secondary outcome measures include binary measures of hypertension (controlled vs uncontrolled), hypertension-related health complications, hospitalizations, and death. The list of possible participants will be generated from a central data warehouse. Randomization will occur after enrollment in the study. Participants will use their assigned BP monitor and join site-specific hypertension interventions. Cross-site learning will occur at regular all-site meetings facilitated by the University of California, Los Angeles Value-Based Care Research Consortium. A pre- and poststudy questionnaire will be conducted to further evaluate participants’ perspectives regarding their BP monitor. Linear mixed effects models will be used to compare the primary outcome measure between study arms. Mixed effects logistic regression models will be used to compare secondary outcome measures between study arms. ResultsThe study will start enrolling participants in the second quarter of 2023 and will be completed by the first half of 2024. Results will be published by the end of 2024. ConclusionsThis pragmatic trial will contribute to the growing field of chronic care management using remote monitoring by answering whether a hypertension intervention coupled with an electronic health record integrated home BP monitor improves patients’ hypertension better than a hypertension intervention with a nonintegrated BP monitor. The outcomes of this study may help health system decision makers determine whether to invest in integrated BP monitors for vulnerable patient populations. Trial RegistrationClinicalTrials.gov NCT05390502; clinicaltrials.gov/study/NCT05390502 International Registered Report Identifier (IRRID)PRR1-10.2196/45915

IntroductionDespite optimal treatment, patients with chronic coronary artery disease (CAD) and diabetes mellitus (DM) are at high risk of cardiovascular events, emphasizing the need for new treatment options. The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD. This analysis determines the efficacy of colchicine in patients with chronic CAD and DM as well as the effect of colchicine on the development of new-onset type 2 diabetes mellitus (T2DM).MethodsThe LoDoCo2 trial randomized 5,522 patients to placebo or colchicine 0.5 mg once daily, with a median follow-up of 28.6 months. The primary composite endpoint was cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven revascularization. The effect of its treatment in patients with and without DM was evaluated by including an interaction term in the model.ResultsA total of 1,007 participants (18.2%) had T2DM at baseline. The adjusted hazard ratio (HR) [(95% confidence interval (CI)] for the primary endpoint in the T2DM group was 1.52 (1.15–2.01, p

IntroductionDeclining hunter populations across North America present wildlife management agencies with the prospect of declining revenues for wildlife conservation and management and the need for new tools to evaluate management strategies and predict future status of game species and hunters.MethodsHere we present a modeling framework and potential decision support tool for managers to link future hunter population dynamics to regulatory restrictiveness, prey abundance, and harvest success. Our hunter model is parameterized based on the authors’ judgment and can be used for demonstration purposes. We simulated three scenarios of restricted harvest, moderate harvest and liberal harvest.ResultsOur simulations show that even though liberal harvest predicts higher cumulative license sales revenue, it corresponds with a slight decline in buck abundance over 10 years. In contrast, highly restrictive harvest corresponds with deer population growth, but a near collapse of hunter populations. Our model demonstrates that managers might face tradeoffs between managing for deer population abundance and hunting revenue and clarifies how these factors might affect decision making.DiscussionThe utility of our tool would be dependent on accessing data on hunter retention and recruitment, however, the strength of our paper is in highlighting a new way of thinking about and potentially addressing these potential tradeoffs. Further, these simulations demonstrate that these tools could be used to evaluate management strategies but also highlight uncertainties, establish research priorities, and potentially design an adaptive management framework.

When plants establish outside their native range, their ability to adapt to the new environment is influenced by both demography and dispersal. However, the relative importance of these two factors is poorly understood. To quantify the influence of demography and dispersal on patterns of genetic diversity underlying adaptation, we used data from a globally distributed demographic research network comprising 35 native and 18 nonnative populations of Plantago lanceolata Species-specific simulation experiments showed that dispersal would dilute demographic influences on genetic diversity at local scales. Populations in the native European range had strong spatial genetic structure associated with geographic distance and precipitation seasonality. In contrast, nonnative populations had weaker spatial genetic structure that was not associated with environmental gradients but with higher within-population genetic diversity. Our findings show that dispersal caused by repeated, long-distance, human-mediated introductions has allowed invasive plant populations to overcome environmental constraints on genetic diversity, even without strong demographic changes. The impact of invasive plants may, therefore, increase with repeated introductions, highlighting the need to constrain future introductions of species even if they already exist in an area.

Depression is a common and disabling disorder in later life, particularly among people with poor physical health. There are many screening tools available that can be used to examine depressive symptoms; however, not all of them may be appropriate or accurate for older adults with cancer. This pilot study was designed to test the diagnostic performance of two screening tools and their short versions in a cohort of vulnerable (G8 score ≤ 14/17) older patients with cancer undergoing comprehensive geriatric assessment (CGA). The prospective analysis covered 50 vulnerable patients with cancer aged ≥70 years. The diagnostic performance of the Geriatric Depression Scale (GDS)-15, GDS-4, Patient Health Questionnaire (PHQ)-9 and PHQ-2 was compared to the ‘gold standard’ Structured Clinical Interview for DSM-5 Disorders (SCID-5-S) depression module A. The sensitivity and specificity in detecting depressive symptoms were the highest in the case of PHQ-2, with an area under the receiver operating characteristic curve (AUROC) of 92.7%. The AUROC for the 9-item version, PHQ-9, was 90.2%. For the GDS-15 and GDS-4, the AUROC was only 56.2% and 62.0%, respectively. The SCREEN pilot study illustrates the potential benefit of using a shorter screening tool, PHQ-2, to identify older patients with cancer who would benefit from a more in-depth emotional evaluation as part of a CGA.

In radiography, an antiscatter grid is a well-known device for eliminating unexpected x-ray scatter. We investigate a new stationary grid artifact suppression method based on a nonsubsampled contourlet transform (NSCT) incorporated with Gaussian band-pass filtering. The proposed method has an advantage that extracts the Moiré components while minimizing the loss of image information and apply the prior information of Moiré component positions in multi-decomposition sub-band images. We implemented the proposed algorithm and performed a simulation and an experiment to demonstrate its viability. We did this experiment using an x-ray tube (M-113T, Varian, focal spot size: 0.1 mm), a flat-panel detector (ROSE-M Sensor, Aspenstate, pixel dimension: 3032 × 3800 pixels, pixel size: 0.076 mm), and carbon graphite-interspaced grids (JPI Healthcare, 18 cm × 24 cm, line density: 103 LP/inch and 150 LP/inch, ratio: 5:1, focal distance: 65 cm). Our results indicate that the proposed method successfully suppressed grid artifacts by reducing them without either reducing the spatial resolution or causing negative side effects. Consequently, we anticipate that the proposed method can improve image acquisition in a stationary grid x-ray system as well as in extended x-ray imaging.

We propose a novel double stripe structure for achieving a narrow far-field angle without significant output power loss in narrow-ridge high-power broad-area laser diodes. By introducing double SiO2 stripes on the top side of the laser diode, we effectively suppress high-order modes through mode weight engineering. Through self-consistent electro-thermal-optical simulations powered by LASTIP with the well-verified model from the reference, we comprehensively analyze and compare the characteristics of high-power broad-area laser diodes utilizing the loss tailoring technique that adopted the much simpler structure compared to prior study and our proposed structure. Our results demonstrate a significant reduction of approximately 36% in the far-field angle while maintaining slope efficiency. This approach shows promise for enhancing the performance of coupling efficiency between narrow-ridge high-power laser diodes and fibers.

The Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) is employed as an intercomparison tool for validating TROPOspheric Monitoring Instrument (TROPOMI) satellite NO2 retrievals against high-resolution Airborne Prism EXperiment (APEX) remote sensing observations performed in June 2019 in the region of Antwerp, a major hotspot of NO2 pollution in Europe. The model is first evaluated using meteorological and chemical observations in this area. Sensitivity simulations varying the model planetary layer boundary (PBL) parameterization were conducted for a 3 d period in June 2019, indicating a generally good performance of most parameterizations against meteorological data (namely ceilometer, surface meteorology, and balloon measurements), except for a moderate overestimation (∼ 1 m s−1) of near-surface wind speed. On average, all but one of the PBL schemes reproduce the surface NO2 measurements at stations of the Belgian Interregional Environmental Agency fairly well, although surface NO2 is generally underestimated during the day (between −4.3 % and −25.1 % on average) and overestimated at night (8.2 %–77.3 %). This discrepancy in the diurnal evolution arises despite (1) implementing a detailed representation of the diurnal cycle of emissions (Crippa et al., 2020) and (2) correcting the modeled concentrations to account for measurement interferences due to NOy reservoir species, which increases NO2 concentrations by about 20 % during the day. The model is further evaluated by comparing a 15 d simulation with surface NO2, NO, CO, and O3 data in the Antwerp region. The modeled daytime NO2 concentrations are more negatively biased during weekdays than during weekends, indicating a misrepresentation of the weekly temporal profile applied to the emissions obtained from Crippa et al. (2020). Using a mass balance approach, we determined a new weekly profile of NOx emissions, leading to a homogenization of the relative bias among the different weekdays. The ratio of weekend to weekday emissions is significantly lower in this updated profile (0.6) than in the profile based on Crippa et al. (2020; 0.84). Comparisons with remote sensing observations generally show a good reproduction of the spatial patterns of NO2 columns by the model. The model underestimated both APEX (by ca. −37 %) and TROPOMI columns (ca. −25 %) on 27 June, whereas no significant bias is found on 29 June. The two datasets are intercompared by using the model as an intermediate platform to account for differences in vertical sensitivity through the application of averaging kernels. The derived bias of TROPOMI v1.3.1 NO2 with respect to APEX is about −10 % for columns between (6–12) × 1015 molec. cm−2. The obtained bias for TROPOMI v1.3.1 increases with the NO2 column, following CAPEX=1.217Cv1.3-0.783 × 1015 molec. cm−2, in line with previous validation campaigns. The bias is slightly lower for the reprocessed TROPOMI v2.3.1, with CAPEX=1.055CPAL-0.437 × 1015 molec. cm−2 (PAL). Finally, a mass balance approach was used to perform a crude inversion of NOx emissions based on 15 d averaged TROPOMI columns. The emission correction is conducted only in regions with high columns and high sensitivity to emission changes in order to minimize the errors due to wind transport. The results suggest that emissions increase over Brussels–Antwerp (+20 %), the Ruhr Valley (13 %), and especially Paris (+39 %), and emissions decrease above a cluster of power plants in western Germany.

Abstract Background Pseudomonas putida has received increasing interest as a cell factory due to its remarkable features such as fast growth, a versatile and robust metabolism, an extensive genetic toolbox and its high tolerance to oxidative stress and toxic compounds. This interest is driven by the need to improve microbial performance to a level that enables biologically possible processes to become economically feasible, thereby fostering the transition from an oil-based economy to a more sustainable bio-based one. To this end, one of the current strategies is to maximize the product-substrate yield of an aerobic biocatalyst such as P. putida during growth on glycolytic carbon sources, such as glycerol and xylose. We demonstrate that this can be achieved by implementing the phosphoketolase shunt, through which pyruvate decarboxylation is prevented, and thus carbon loss is minimized. Results In this study, we introduced the phosphoketolase shunt in the metabolism of P. putida KT2440. To maximize the effect of this pathway, we first tested and selected a phosphoketolase (Xfpk) enzyme with high activity in P. putida. Results of the enzymatic assays revealed that the most efficient Xfpk was the one isolated from Bifidobacterium breve. Using this enzyme, we improved the P. putida growth rate on glycerol and xylose by 44 and 167%, respectively, as well as the biomass yield quantified by OD600 by 50 and 30%, respectively. Finally, we demonstrated the impact on product formation and achieved a 38.5% increase in mevalonate and a 25.9% increase in flaviolin yield from glycerol. A similar effect was observed on the mevalonate-xylose and flaviolin-xylose yields, which increased by 48.7 and 49.4%, respectively. Conclusions Pseudomonas putida with the implemented Xfpk shunt grew faster, reached a higher final OD600nm and provided better product-substrate yields than the wild type. By reducing the pyruvate decarboxylation flux, we significantly improved the performance of this important workhorse for industrial applications. This work encompasses the first steps towards full implementation of the non-oxidative glycolysis (NOG) or the glycolysis alternative high carbon yield cycle (GATCHYC), in which a substrate is converted into products without CO2 loss These enhanced properties of P. putida will be crucial for its subsequent use in a range of industrial processes.

Objective: Breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a sensitive imaging technique critical for breast cancer diagnosis. However, the administration of contrast agents poses a potential risk. This can be avoided if contrast-enhanced MRI can be obtained without using contrast agents. Thus, we aimed to generate T1-weighted contrast-enhanced MRI (ceT1) images from pre-contrast T1 weighted MRI (preT1) images in the breast. Methods: We proposed a generative adversarial network to synthesize ceT1 from preT1 breast images that adopted a local discriminator and segmentation task network to focus specifically on the tumor region in addition to the whole breast. The segmentation network performed a related task of segmentation of the tumor region, which allowed important tumor-related information to be enhanced. In addition, edge maps were included to provide explicit shape and structural information. Our approach was evaluated and compared with other methods in the local (n = 306) and external validation (n = 140) cohorts. Four evaluation metrics of normalized mean squared error (NRMSE), Pearson cross-correlation coefficients (CC), peak signal-to-noise ratio (PSNR), and structural similarity index map (SSIM) for the whole breast and tumor region were measured. An ablation study was performed to evaluate the incremental benefits of various components in our approach. Results: Our approach performed the best with an NRMSE 25.65, PSNR 54.80 dB, SSIM 0.91, and CC 0.88 on average, in the local test set. Conclusion: Performance gains were replicated in the validation cohort. Significance: We hope that our method will help patients avoid potentially harmful contrast agents. Clinical and Translational Impact Statement—Contrast agents are necessary to obtain DCE-MRI which is essential in breast cancer diagnosis. However, administration of contrast agents may cause side effects such as nephrogenic systemic fibrosis and risk of toxic residue deposits. Our approach can generate DCE-MRI without contrast agents using a generative deep neural network. Thus, our approach could help patients avoid potentially harmful contrast agents resulting in an improved diagnosis and treatment workflow for breast cancer.

Highlights Graphene (Gr)-bridge heterostructure, consisting of a laterally series-connected (cascade) ambipolar/Gr/n-type 2D van der Waals channel materials for ambipolar semiconductor-based high-end application devices was developed. Non-classical transfer characteristics (humped curve) in FET operation and negative differential transconductances were observed. Gr-bridge heterostructure device with PdSe2 (narrow bandgap) allows multi-value logic operation while WSe2 (wide bandgap) enables frequency tripler circuit operation.

Objectives. We aimed to assess the genetic differences between cases of early-stage tongue cancer that were positive or negative for lymph node metastasis. Methods. In total, 35 cases of tongue cancer with RNA sequencing data were enrolled in this study. The gene expression profile of the following two groups was compared: N0 group (T stage 1 or 2 with N0 stage) and N+ group (T stage 1 or 2 with N+ stage). Using the R and limma packages in the Bioconductor program, we extracted the differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) online tool. Immune cell infiltration was analyzed using the CIBERSORT online program. Immunochemical staining of the cancer tissue was evaluated and The Cancer Genome Atlas (TCGA) data were analyzed to validate the identified DEGs. Results. No significant differences were found in the infiltration of 22 types of immune cells. Among a total of 51 identified DEGs, 14 genes were significantly upregulated, while 37 genes were significantly downregulated (P2). Pathway analysis revealed significant associations with the arachidonic acid metabolism-related pathway, calcium signaling, and the muscle contraction pathway. The following DEGs were the most significantly different between the two groups: DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, and FAM25A. TCGA data showed that DEFB4A and DEFB103B were more highly expressed in the N0 group than in the N+ group, although the difference did not achieve statistical significance. Immunochemical staining of cancer tissue revealed significantly higher expression of defensin in the N0 group. Conclusions. Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer.

Abstract Background Surgeons are commonly evaluated by surgical skills and outcomes rather than their character traits. We sought to examine role model behaviours of senior surgeons through the lens of Aristotelian (virtue) ethics. Methods Semi-structured focus group interviews were undertaken of anaesthetic trainees at a large university hospital NHS Foundation Trust and transcripts were subjected to thematic analysis to yield themes and subthemes. Participation of the trainees was entirely voluntary and focus groups were conducted using Zoom™. Results The overarching themes identified were ‘Teamwork makes the dream work’, ‘Captain of the ship’ and ‘Strong foundations’. Conclusion We hope to take lessons learnt in conjunction with our previous work to help refocus surgical training towards a process of character reformation, rather than simply imparting technical skills to trainees.

Abstract Background We hypothesized that posterior osteotomy prior to ACR (Anterior column realignment) through P-A-P surgical sequence would permit a greater correction for deformity corrective surgery than the traditional A-P sequence without posterior osteotomy. This study aimed to determine the impact of the P-A-P sequence on the restoration of lumbar lordosis (LL) compared to the A-P sequence in deformity corrective surgery for adult spinal deformity (ASD) patients and to identify the characteristics of patients who require this sequence. Methods Between 2017 and 2019, 260 ASD patients who had undergone combined corrective surgery were reviewed retrospectively. This study included 178 patients who underwent posterior osteotomy before the ACR (P-A group) and 82 patients who underwent the A-P sequence (A-P group). Sagittal spinopelvic parameters were determined from pre- and postoperative whole-spine radiographs and compared between the groups. To find better indications for the P-A-P sequence, we conducted additional analysis on postoperative outcomes of patients in the A-P group. Results The P-A group showed a significantly higher change in LL (53.7° vs. 44.3°, p

Abstract A fundamental parameter-based quantification scheme for confocal XRF was applied to sub-micron synchrotron radiation X-ray fluorescence (SR-XRF) data obtained at the beamline P06 of the Deutsches Elektronen-Synchrotron (DESY, Hamburg, Germany) from two sections C0033-01 and C0033-04 that were wet cut from rock fragment C0033 collected from Cb-type asteroid (162173) Ryugu by JAXA’s Hayabusa2 mission. Trace-element quantifications show that C0033 bulk matrix is CI-like, whereas individual mineral grains (i.e., magnetite, pyrrhotite, dolomite, apatite and breunnerite) show, depending on the respective phase, minor to strong deviations. The non-destructive nature of SR-XRF coupled with a new PyMca (a Python toolkit for XRF data analysis)-based quantification approach, performed in parallel with the synchrotron experiments, proves to be an attractive tool for the initial analysis of samples from return missions, such as Hayabusa2 and OSIRIS-REx, the latter returning material from a B-type asteroid (101955) Bennu in 2023. Graphical Abstract

Abstract Introduction Macrolide‐resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and macrolide‐sensitive M. pneumoniae (MSMP) and identified factors associated with prolonged hospital admission in children. Methods A prospective multicenter study was conducted in 1063 children

Urolithiasis is a condition which is commonly encountered in practice, however retrograde migration of a calculus within the ureter has only recently been documented with few cases reported in the literature. We present the case of a 47-year-old woman presenting with symptomatic urolithiasis confirmed by CT who recovered from her symptoms only for it to be discovered that the calculus had undergone retrograde migration into the renal calyx on a follow up CT examination. We theorise that retrograde urolithiasis migration may be an innate safety mechanism that evolved to prevent complications and/or death from urolithiasis impaction by attempting to return a migrated lithiasis to the renal calyx.

In this data paper, we present a specimen-based occurrence dataset compiled in the framework of the Conservation of Endemic Central African Trees (ECAT) project with the aim of producing global conservation assessments for the IUCN Red List. The project targets all tree species endemic or sub-endemic to the Central African region comprising the Democratic Republic of the Congo (DR Congo), Rwanda, and Burundi. The dataset contains 6361 plant collection records with occurrences of 8910 specimens from 337 taxa belonging to 153 genera in 52 families. Many of these tree taxa have restricted geographic ranges and are only known from a small number of herbarium specimens. As assessments for such taxa can be compromised by inadequate data, we transcribed and geo-referenced specimen label information to obtain a more accurate and complete locality dataset. All specimen data were manually cleaned and verified by botanical experts, resulting in improved data quality and consistency.

The Korea Atomic Energy Research Institute (KAERI) is planning the construction of the KIJANG Research Reactor (KJRR) for stable supply of 99Mo. The Fission 99Mo Production Process (FMPP) of KJRR produces solid waste such as spent uranium cake and alumina cake, and liquid waste in the form of intermediate level liquid waste (ILLW) and low level liquid waste (LLLW). This study thus established the operating range and optimum operating conditions for the cementation of ILLW from FMPP. It also evaluated whether cement waste form samples produced under optimum operational conditions satisfy the waste acceptance criteria (WAC) of a disposal facility in Korea (Korea radioactive waste agency, KORAD). Considering economic feasibility and safety, optimum operational conditions were achieved at a w/c ratio of 0.55, and the corresponding salt content was 5.71 wt%. The cement waste form samples prepared under optimum operational conditions were found to satisfy KORAD's WAC when tested for structural stability and leachability. The results indicate that the proposed cementation conditions for the disposal of ILLW from FMMP can be effectively applied to KJRR's disposal facility.