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RAGE (receptor for advanced glycation end-products) represents a class of multi-ligand pattern recognition receptors highly expressed in the vertebrate lung. Our previous work demonstrated unique patterns of RAGE expression in the developing murine lung and regulation by key transcription factors including NKX2.1 and FoxA2. The current investigation employed conditional lung-specific upregulation via a TetOn transgenic mouse model (RAGE TG) and nontransgenic controls. RAGE expression was induced in RAGE TG mice throughout gestation (embryonic day, E0-E18.5) or from E15.5-E18.5 and compared to age-matched controls. High-resolution respirometry was used to assess mitochondrial respiration and context was provided by quantifying ATP and reactive oxygen species (ROS) generation. Lung lysates were also screened by immunoblotting for MAPK/PI3K signaling intermediates. RAGE upregulation increased mitochondrial oxygen consumption in the E0-E18.5 and E15.5-E18.5 groups compared to controls. RAGE TG mice also had increased ATP concentrations, which persisted even after controlling for oxygen consumption. In contrast, ROS generation was diminished in RAGE TG animals compared to controls. Lastly, in both RAGE TG groups, pERK and pp38 were significantly decreased, whereas pAKT was significantly elevated, suggesting that RAGE signaling is likely perpetuated via pAKT pathways. Together, these data demonstrate that despite lung hypoplasia in RAGE TG mice, the remaining tissue experiences a favorable shift in mitochondrial bioenergetics without excessive redox assault and a preference for AKT signaling over ERK or p38.

Introduction: Dermatological conditions affecting the nails can manifest differently in individuals with distinct skin tones. This often leads to difficulty in the recognition of nail diseases especially in people with skin of color (SoC), that result not well represented in the literature. Objectives: Our aim was to provide dermatologists with useful clues for prompt recognition and diagnosis of nail psoriasis (NPso) and nail lichen planus (NLP) in people with SoC. Methods: We described the ungual manifestations of NPso and NLP in a population of 30 patients with SoC. Diagnosis was primarily based on clinical examination; in cases of diagnostic uncertainty, a biopsy of the nail matrix was performed to obtain histological conclusive evidence. Results: Of the 30 people with SoC in the analysis, 24 patients had NPso with a median Fitzpatrick phototype of 4.77 and 6 patients had NLP with a median Fitzpatrick phototype of 5. Regarding the 24 patients with NPso, 10 presented with trachyonychia, 9 displayed nail pitting, 8 showed onycholysis, 12 had subungual hyperkeratosis, while splinter hemorrhages were visible in 2 patients and activation melanonychia was discernible on the nail plates of 8 patients. Over the 6 patients diagnosed with NLP, all of them had post-inflammatory pigmentation on the proximal nail, with 3 patients exhibiting trachyonychia and 3 others having longitudinal fissures; subungual hyperkeratosis was found in 5 patients, while 3 patients displayed activated melanonychia. Conclusion: People with SoC exhibit a peculiar clinical presentation of both NPso and NLP and a better understanding is essential for providing timely and effective care.

Abstract Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5’ untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN.

Summary: Background: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics. Methods: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein–protein interaction networks and drug repurposing analyses between high-risk groups. Findings: We examined two high-risk omics-defined groups in non-overlapping test sets (n = 1133 NHW COPDGene, n = 299 African American (AA) COPDGene, n = 468 ECLIPSE). We defined “high activity” (low PRS, high TRS) and “severe risk” (high PRS, high TRS) subgroups. Participants in both subgroups had lower body-mass index (BMI), lower lung function, and alterations in metabolic, growth, and immune signalling processes compared to a low-risk (low PRS, low TRS) subgroup. “High activity” but not “severe risk” participants had greater prospective FEV1 decline (COPDGene: −51 mL/year; ECLIPSE: −40 mL/year) and proteomic profiles were enriched in gene sets perturbed by treatment with 5-lipoxygenase inhibitors and angiotensin-converting enzyme (ACE) inhibitors. Interpretation: Concomitant use of polygenic and transcriptional risk scores identified clinical and molecular heterogeneity amongst high-risk individuals. Proteomic and drug repurposing analysis identified subtype-specific enrichment for therapies and suggest prior drug repurposing failures may be explained by patient selection. Funding: National Institutes of Health.

Abstract While studies show links between smartphone data and affective symptoms, we lack clarity on the temporal scale, specificity (e.g., to depression vs. anxiety), and person-specific (vs. group-level) nature of these associations. We conducted a large-scale (n = 1013) smartphone-based passive sensing study to identify within- and between-person digital markers of depression and anxiety symptoms over time. Participants (74.6% female; M age = 40.9) downloaded the LifeSense app, which facilitated continuous passive data collection (e.g., GPS, app and device use, communication) across 16 weeks. Hierarchical linear regression models tested the within- and between-person associations of 2-week windows of passively sensed data with depression (PHQ-8) or generalized anxiety (GAD-7). We used a shifting window to understand the time scale at which sensed features relate to mental health symptoms, predicting symptoms 2 weeks in the future (distal prediction), 1 week in the future (medial prediction), and 0 weeks in the future (proximal prediction). Spending more time at home relative to one’s average was an early signal of PHQ-8 severity (distal β = 0.219, p = 0.012) and continued to relate to PHQ-8 at medial (β = 0.198, p = 0.022) and proximal (β = 0.183, p = 0.045) windows. In contrast, circadian movement was proximally related to (β = −0.131, p = 0.035) but did not predict (distal β = 0.034, p = 0.577; medial β = −0.089, p = 0.138) PHQ-8. Distinct communication features (i.e., call/text or app-based messaging) related to PHQ-8 and GAD-7. Findings have implications for identifying novel treatment targets, personalizing digital mental health interventions, and enhancing traditional patient-provider interactions. Certain features (e.g., circadian movement) may represent correlates but not true prospective indicators of affective symptoms. Conversely, other features like home duration may be such early signals of intra-individual symptom change, indicating the potential utility of prophylactic intervention (e.g., behavioral activation) in response to person-specific increases in these signals.

Exposure to secondhand smoke (SHS) during fetal development results in negative postnatal effects, including altered organ development, changes in metabolism, and increased risk of respiratory illness. Previously, we found the induction of intrauterine growth restriction (IUGR) dependent on the expression of the receptor for advanced glycation end-products (RAGE) in mice treated with SHS. Furthermore, antenatal SHS exposure increases RAGE expression in the fetal lung. Our objective was to determine the postnatal effects of antenatal SHS treatment in 4- and 12-week-old offspring. Pregnant animals were treated with SHS via a nose-only delivery system (Scireq Scientific, Montreal, Canada) for 4 days (embryonic day 14.5 through 18.5), and offspring were evaluated at 4 or 12 weeks of age. Animal and organ weights were measured, and lungs were histologically characterized. Blood pressure and heart rates were obtained, and RAGE protein expression was determined in the lungs of control and treated animals. We observed the following: (1) significant decreases in animal, liver, and heart weights at 4 weeks of age; (2) increased blood pressure in 4-week-old animals; and (3) increased RAGE expression in the lungs of the 4-week-old animals. Our results suggest an improvement in these metrics by 12 weeks postnatally such that measures were not different regardless of RA or SHS exposure. Increased RAGE expression in lungs from 4-week-old mice antenatally treated with SHS suggests a possible role for this important smoke-mediated receptor in establishing adult disease following IUGR pregnancies.

A woman with recent personalized external aortic root support implant presented in cardiogenic shock with bilateral coronary ostial occlusion and aortic inflammation requiring emergency coronary angioplasty. Subsequent computed tomography with positron emission tomography scanning demonstrated aortitis with extensive inflammation adjacent to the personalized external aortic root support mesh, the first report of this important complication.

Abstract Background Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality. Methods In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles from plasma samples using liquid chromatography–mass spectrometry (Metabolon). We assessed the associations between metabolite levels and QIA using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use, at a Benjamini–Hochberg False Discovery Rate p-value of ≤ 0.05. Using multinomial regression models adjusted for these covariates, we assessed the associations between metabolite levels and the following CT phenotypes: QIA-predominant, emphysema-predominant, combined-predominant, and neither- predominant. Pathway enrichment analyses were performed using MetaboAnalyst. Results We found 85 metabolites significantly associated with QIA, with overrepresentation of the nicotinate and nicotinamide, histidine, starch and sucrose, pyrimidine, phosphatidylcholine, lysophospholipid, and sphingomyelin pathways. These included metabolites involved in inflammation and immune response, extracellular matrix remodeling, surfactant, and muscle cachexia. There were 75 metabolites significantly different between QIA-predominant and emphysema-predominant phenotypes, with overrepresentation of the phosphatidylethanolamine, nicotinate and nicotinamide, aminoacyl-tRNA, arginine, proline, alanine, aspartate, and glutamate pathways. Conclusions Metabolomic correlates may lend insight to the biologic perturbations and pathways that underlie clinically meaningful quantitative CT measurements like QIA in smokers.

Abstract The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed and obtained IRB approval for a process of returning HCV research results and an HCV Follow-Up Study questionnaire to capture information about previous HCV diagnosis and treatment information and participant reactions to return of HCV results. During phone calls following the initial HCV notification letter, 84 of 124 participants who could be contacted (67.7%) volunteered that they had been previously diagnosed with HCV infection. Thirty-one of these 124 COPDGene participants were enrolled in the HCV Follow-Up Study. Five of the 31 HCV Follow-Up Study participants did not report a previous diagnosis of HCV. For four of these participants, subsequent clinical HCV testing confirmed HCV infection. Thus, 30/31 Follow-Up Study participants had confirmed HCV diagnoses, supporting the accuracy of the HCV research test results. However, the limited number of participants in the Follow-Up Study precludes an accurate assessment of the false-positive and false-negative rates of the research RNA sequencing evidence for HCV. Most HCV Follow-Up Study participants (29/31) were supportive of returning HCV research results, and most participants found the process for returning HCV results to be informative and not upsetting. Newly diagnosed participants were more likely to be pleased to learn about a potentially curable infection (p = 0.027) and showed a trend toward being more frightened by the potential health risks of HCV (p = 0.11). We conclude that HCV results identified incidentally during transcriptomic research studies can be successfully returned to research study participants with a carefully designed process.

Previous studies involving workers at brick kilns in the Kathmandu Valley of Nepal have investigated chronic exposure to hazardous levels of fine particulate matter (PM2.5) common in ambient and occupational environments. Such exposures are known to cause and/or exacerbate chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma. However, there is a paucity of data regarding the status of systemic inflammation observed in exposed workers at brick manufacturing facilities within the country. In the current study, we sought to elucidate systemic inflammatory responses by quantifying the molecular cytokine/chemokine profiles in serum from the study participants. A sample of participants were screened from a kiln in Bhaktapur, Nepal (n = 32; 53% female; mean ± standard deviation: 28.42 ± 11.47 years old) and grouped according to job category. Blood was procured from participants on-site, allowed to clot at room temperature, and centrifuged to obtain total serum. A human cytokine antibody array was used to screen the inflammatory mediators in serum samples from each of the participants. For the current study, four job categories were evaluated with n = 8 for each. Comparisons were generated between a control group of administration workers vs. fire master workers, administration workers vs. green brick hand molders, and administration workers vs. top loaders. We discovered significantly increased concentrations of eotaxin-1, eotaxin-2, GCSF, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, TGF-β1, TNF-α, and TIMP-2 in serum samples from fire master workers vs. administration workers (p < 0.05). Each of these molecules was also significantly elevated in serum from green brick hand molders compared to administration workers (p < 0.05). Further, each molecule in the inflammatory screening with the exception of TIMP-2 was significantly elevated in serum from top loaders compared to administration workers (p < 0.05). With few exceptions, the fire master workers expressed significantly more systemic inflammatory molecular abundance when compared to all other job categories. These results reveal an association between pulmonary exposure to PM2.5 and systemic inflammatory responses likely mediated by cytokine/chemokine elaboration. The additional characterization of a broader array of inflammatory molecules may provide valuable insight into the susceptibility to lung diseases among this population.

Abstract Privacy protection is a core principle of genomic but not proteomic research. We identified independent single nucleotide polymorphism (SNP) quantitative trait loci (pQTL) from COPDGene and Jackson Heart Study (JHS), calculated continuous protein level genotype probabilities, and then applied a naïve Bayesian approach to link SomaScan 1.3K proteomes to genomes for 2812 independent subjects from COPDGene, JHS, SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) and Multi-Ethnic Study of Atherosclerosis (MESA). We correctly linked 90–95% of proteomes to their correct genome and for 95–99% we identify the 1% most likely links. The linking accuracy in subjects with African ancestry was lower (~ 60%) unless training included diverse subjects. With larger profiling (SomaScan 5K) in the Atherosclerosis Risk Communities (ARIC) correct identification was > 99% even in mixed ancestry populations. We also linked proteomes-to-proteomes and used the proteome only to determine features such as sex, ancestry, and first-degree relatives. When serial proteomes are available, the linking algorithm can be used to identify and correct mislabeled samples. This work also demonstrates the importance of including diverse populations in omics research and that large proteomic datasets (> 1000 proteins) can be accurately linked to a specific genome through pQTL knowledge and should not be considered unidentifiable.

Background: Prior literature links passively sensed information about a person's location, movement, and communication with social anxiety. These findings hold promise for identifying novel treatment targets, informing clinical care, and personalizing digital mental health interventions. However, social anxiety symptoms are heterogeneous; to identify more precise targets and tailor treatments, there is a need for personal sensing studies aimed at understanding differential predictors of the distinct subdomains of social anxiety. Our objective was to conduct a large-scale smartphone-based sensing study of fear, avoidance, and physiological symptoms in the context of trait social anxiety over time. Methods: Participants (n = 1013; 74.6 % female; M age = 40.9) downloaded the LifeSense app, which collected continuous passive data (e.g., GPS, communication, app and device use) over 16 weeks. We tested a series of multilevel linear regression models to understand within- and between-person associations of 2-week windows of passively sensed smartphone data with fear, avoidance, and physiological distress on the self-reported Social Phobia Inventory (SPIN). A shifting sensor lag was applied to examine how smartphone features related to SPIN subdomains 2 weeks in the future (distal prediction), 1 week in the future (medial prediction), and 0 weeks in the future (proximal prediction). Results: A decrease in time visiting novel places was a strong between-person predictor of social avoidance over time (distal β = −0.886, p = .002; medial β = −0.647, p = .029; proximal β = −0.818, p = .007). Reductions in call- and text-based communications were associated with social avoidance at both the between- (distal β = −0.882, p = .002; medial β = −0.932, p = .001; proximal β = −0.918, p = .001) and within- (distal β = −0.191, p = .046; medial β = −0.213, p = .028) person levels, as well as between-person fear of social situations (distal β = −0.860, p

Abstract Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV1) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV1 decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.

Abstract Pregnancy is a dynamic process associated with profound hormonally mediated haemodynamic changes which result in structural and functional adaptations in the cardiovascular system. An understanding of the myocardial adaptations is important for echocardiographers and clinicians undertaking or interpreting echocardiograms on pregnant and post-partum women. This guideline, on behalf of the British Society of Echocardiography and United Kingdom Maternal Cardiology Society, reviews the expected echocardiographic findings in normal pregnancy and in different cardiac disease states, as well as echocardiographic signs of decompensation. It aims to lay out a structure for echocardiographic scanning and surveillance during and after pregnancy as well as suggesting practical advice on scanning pregnant women.

Background: Effective therapeutics for severe acute respiratory syndrome CoronaVirus-2 (SARS-CoV-2) infection are evolving. Under Emergency Use Authorization, COVID-19 convalescent plasma (CCP) was widely used in individuals hospitalized for COVID-19, but few randomized controlled trials supported its efficacy to limit respiratory failure or death. Methods: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1) was a double-blind, multi-site, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of CCP with conventional therapy in hospitalized Veterans with SARS-CoV-2 infection and early respiratory compromise (requirement for oxygen). Participants (planned sample size 702) were randomized 1:1 to receive CCP with high titer neutralizing activity or 0.9% saline, stratified by site and age (≥65 versus

Abstract Background Airway macrophages (AM), crucial for the immune response in chronic obstructive pulmonary disease (COPD), are exposed to environmental particulate matter (PM), which they retain in their cytoplasm as black carbon (BC). However, whether AM BC accurately reflects environmental PM2.5 exposure, and can serve as a biomarker of COPD outcomes, is unknown. Methods We analyzed induced sputum from participants at 7 of 12 sites SPIROMICS sites for AM BC content, which we related to exposures and to lung function and respiratory outcomes. Models were adjusted for batch (first vs. second), age, race (white vs. non-white), income (

Hyper-secretion and/or hyper-concentration of mucus is a defining feature of multiple obstructive lung diseases, including chronic obstructive pulmonary disease (COPD). Mucus itself is composed of a mixture of water, ions, salt and proteins, of which the gel-forming mucins, MUC5AC and MUC5B, are the most abundant. Recent studies have linked the concentrations of these proteins in sputum to COPD phenotypes, including chronic bronchitis (CB) and acute exacerbations (AE). We sought to determine whether common genetic variants influence sputum mucin concentrations and whether these variants are also associated with COPD phenotypes, specifically CB and AE. We performed a GWAS to identify quantitative trait loci for sputum mucin protein concentration (pQTL) in the Sub-Populations and InteRmediate Outcome Measures in COPD Study (SPIROMICS, n = 708 for total mucin, n = 215 for MUC5AC, MUC5B). Subsequently, we tested for associations of mucin pQTL with CB and AE using regression modeling (n = 822-1300). Replication analysis was conducted using data from COPDGene (n = 5740) and by examining results from the UK Biobank. We identified one genome-wide significant pQTL for MUC5AC (rs75401036) and two for MUC5B (rs140324259, rs10001928). The strongest association for MUC5B, with rs140324259 on chromosome 11, explained 14% of variation in sputum MUC5B. Despite being associated with lower MUC5B, the C allele of rs140324259 conferred increased risk of CB (odds ratio (OR) = 1.42; 95% confidence interval (CI): 1.10-1.80) as well as AE ascertained over three years of follow up (OR = 1.41; 95% CI: 1.02-1.94). Associations between rs140324259 and CB or AE did not replicate in COPDGene. However, in the UK Biobank, rs140324259 was associated with phenotypes that define CB, namely chronic mucus production and cough, again with the C allele conferring increased risk. We conclude that sputum MUC5AC and MUC5B concentrations are associated with common genetic variants, and the top locus for MUC5B may influence COPD phenotypes, in particular CB.

We report here a pilot trial that mainly aimed to assess the endogenous secretion of oxytocin (OXT) in patients with Borderline personality disorder (BPD) and healthy controls. It is the first trial with BPD using salivary OXT and studying its reactivity in a natural setting and an experimental stress task. Compared to controls, patients with BPD showed lower variation of OXT in the natural setting and lower OXT reactivity during the stress task, contrasting to higher perceived stress and anger states. We confirm the feasibility of the protocol. Our results encourage the implementation of a larger trial to address specific hypotheses.

The application of clustering algorithms to the Gaia astrometric catalog has revolutionized our census of stellar populations in the milky Way, including the discovery of many new dispersed structures. We focus on one such structure, Theia 456 (COIN-Gaia-13), a loosely bound collection of ∼320 stars spanning ∼120 pc that has previously been shown to exhibit kinematic, chemical, and gyrochronal coherency, indicating a common origin. We obtain follow-up radial velocities and supplement these with Gaia astrometry to perform an in-depth dynamical analysis of Theia 456. By integrating stellar orbits through a Milky Way potential, we find the currently dispersed structure coalesced into a small cluster in the past. Via Bayesian modeling, we derive a kinematic age of 245 ± 3 Myr (statistical), a half-mass–radius of 9 ± 2 pc, and an initial one-dimensional velocity dispersion of 0.14 ± 0.02 km s ^−1 . Our results are entirely independent of model isochrones, details of stellar evolution, and internal cluster dynamics, and the statistical precision in our age derivation rivals that of the most precise age-dating techniques known today, though our imperfect knowledge of the Milky Way potential and simple spherical model for Theia 456 at birth add additional uncertainties. Using posterior predictive checking, we confirm these results are robust under reasonable variations to the Milky Way potential. Such low-density structures that are disrupted by the Galactic tides before virializing may be ubiquitous, signifying that Theia 456 is a valuable benchmark for studying the dynamical history of stellar populations in the Milky Way.

Recently Gagné et al. suggested that young moving groups with similar kinematic properties could be part of larger dissolving structures. One example was IC 2602 as the core of a group of associations, including its corona (CIC 2602), Tucana-Horologium (THA), and parts of Theia 92. We explore this hypothesis by measuring the rotation periods of 953 objects selected using Gaia DR3 kinematics from IC 2602, CIC 2602, Theia 92, and a newly identified group of stars that bridge IC 2602 and THA. We use Transiting Exoplanet Survey Satellite (TESS) full frame images to measure new rotation periods and combine these with the rotation periods for THA from Popinchalk et al. to compare their rotation period distributions and other youth indicators where available to examine if the groups could be coeval. We find strong agreement between the rotation distributions of IC 2602, CIC 2602, and THA, suggesting a shared age of ∼40 Myr, and which in combination could serve as an example of a typical distribution at this age. Theia 92 does not agree at the same level, and we explore the potential kinematic reasons it does not match the rotation period distribution of the larger groups. Additionally, in our light curve analysis we identify ∼50 potential binaries, as well as four new M dwarf complex rotators that show major morphological changes between TESS cycles. Finally, using the amplitudes of the rotation periods we measured, we find strong agreement with the amplitude–age relation presented in Morris for our 40 Myr groups.

Low-mass (≲1.2 M _⊙ ) main-sequence stars lose angular momentum over time, leading to a decrease in their magnetic activity. The details of this rotation–activity relation remain poorly understood, however. Using observations of members of the ≈700 Myr old Praesepe and Hyades open clusters, we aim to characterize the rotation–activity relation for different tracers of activity at this age. To complement published data, we obtained new optical spectra for 250 Praesepe stars, new X-ray detections for 10, and new rotation periods for 28. These numbers for Hyads are 131, 23, and 137, respectively. The latter increases the number of Hyads with periods by 50%. We used these data to measure the fractional H α and X-ray luminosities, L _H _α / L _bol and L _X / L _bol , and to calculate Rossby numbers R _o . We found that at ≈700 Myr almost all M dwarfs exhibit H α emission, with binaries having the same overall color–H α equivalent width distribution as single stars. In the R _o – L _H _α / L _bol plane, unsaturated single stars follow a power law with index β = −5.9 ± 0.8 for R _o > 0.3. In the R _o – L _X / L _bol plane, we see evidence for supersaturation for single stars with R _o ≲ 0.01, following a power law with index ${\beta }_{\sup }={0.5}_{-0.1}^{+0.2}$ , supporting the hypothesis that the coronae of these stars are being centrifugally stripped. We found that the critical R _o value at which activity saturates is smaller for L _X / L _bol than for L _H _α / L _bol . Finally, we observed an almost 1:1 relation between L _H _α / L _bol and L _X / L _bol , suggesting that both the corona and the chromosphere experience similar magnetic heating.

Purpose: The purpose of this study was to train and validate machine learning models for predicting rapid decline of forced expiratory volume in 1 s (FEV1) in individuals with a smoking history at-risk-for chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease (GOLD 0), or with mild-to-moderate (GOLD 1–2) COPD. We trained multiple models to predict rapid FEV1 decline using demographic, clinical and radiologic biomarker data. Training and internal validation data were obtained from the COPDGene study and prediction models were validated against the SPIROMICS cohort.Methods: We used GOLD 0–2 participants (n = 3,821) from COPDGene (60.0 ± 8.8 years, 49.9% male) for variable selection and model training. Accelerated lung function decline was defined as a mean drop in FEV1% predicted of > 1.5%/year at 5-year follow-up. We built logistic regression models predicting accelerated decline based on 22 chest CT imaging biomarker, pulmonary function, symptom, and demographic features. Models were validated using n = 885 SPIROMICS subjects (63.6 ± 8.6 years, 47.8% male).Results: The most important variables for predicting FEV1 decline in GOLD 0 participants were bronchodilator responsiveness (BDR), post bronchodilator FEV1% predicted (FEV1.pp.post), and CT-derived expiratory lung volume; among GOLD 1 and 2 subjects, they were BDR, age, and PRMlower lobes fSAD. In the validation cohort, GOLD 0 and GOLD 1–2 full variable models had significant predictive performance with AUCs of 0.620 ± 0.081 (p = 0.041) and 0.640 ± 0.059 (p < 0.001). Subjects with higher model-derived risk scores had significantly greater odds of FEV1 decline than those with lower scores.Conclusion: Predicting FEV1 decline in at-risk patients remains challenging but a combination of clinical, physiologic and imaging variables provided the best performance across two COPD cohorts.

Abstract Background Smoke exposure culminates as a progressive lung complication involving airway inflammation and remodeling. While primary smoke poses the greatest risk, nearly half of the US population is also at risk due to exposure to secondhand smoke (SHS). Methods We used WT, RAGE−/− (KO), and Tet-inducible lung-specific RAGE overexpressing transgenic (TG) mice to study the role of RAGE during short-term responses to SHS. We evaluated SHS effects in mice with and without semi-synthetic glycosaminoglycan ethers (SAGEs), which are anionic, partially lipophilic sulfated polysaccharide derivatives known to inhibit RAGE signaling. TG Mice were weaned and fed doxycycline to induce RAGE at postnatal day (PN) 30. At PN40, mice from each line were exposed to room air (RA) or SHS from three Kentucky 3R4F research cigarettes via a nose-only delivery system (Scireq Scientific, Montreal, Canada) five days a week and i.p. injections of PBS or SAGE (30 mg/kg body weight) occurred three times per week from PN40-70 before mice were sacrificed on PN70. Results RAGE mRNA and protein expression was elevated following SHS exposure of control and TG mice and not detected in RAGE KO mice. Bronchoalveolar lavage fluid (BALF) analysis revealed RAGE-mediated influence on inflammatory cell diapedesis, total protein, and pro-inflammatory mediators following exposure. Lung histological assessment revealed indistinguishable morphology following exposure, yet parenchymal apoptosis was increased. Inflammatory signaling intermediates such as Ras and NF-κB, as well as downstream responses were influenced by the availability of RAGE, as evidenced by RAGE KO and SAGE treatment. Conclusions These data provide fascinating insight suggesting therapeutic potential for the use of RAGE inhibitors in lungs exposed to SHS smoke.

Abstract Background The COVID-19 pandemic has placed exceptional demand on Intensive Care Units, necessitating the critical care transfer of patients on a regional and national scale. Performing these transfers required specialist expertise and involved moving patients over significant distances. Air Ambulance Kent Surrey Sussex created a designated critical care transfer team and was one of the first civilian air ambulances in the United Kingdom to move ventilated COVID-19 patients by air. We describe the practical set up of such a service and the key lessons learned from the first 50 transfers. Methods Retrospective review of air critical care transfer service set up and case review of first 50 transfers. Results We describe key elements of the critical care transfer service, including coordination and activation; case interrogation; workforce; training; equipment; aircraft modifications; human factors and clinical governance. A total of 50 missions are described between 18 December 2020 and 1 February 2021. 94% of the transfer missions were conducted by road. The mean age of these patients was 58 years (29–83). 30 (60%) were male and 20 (40%) were female. The mean total mission cycle (time of referral until the time team declared free at receiving hospital) was 264 min (range 149–440 min). The mean time spent at the referring hospital prior to leaving for the receiving unit was 72 min (31–158). The mean transfer transit time between referring and receiving units was 72 min (9–182). Conclusion Critically ill COVID-19 patients have highly complex medical needs during transport. Critical care transfer of COVID-19-positive patients by civilian HEMS services, including air transfer, can be achieved safely with specific planning, protocols and precautions. Regional planning of COVID-19 critical care transfers is required to optimise the time available of critical care transfer teams.

Background. Time to treatment initiation (TTI) is a quality metric in cancer care. The purpose of this study is to determine the accuracy of TTI data from a single cancer center registry that reports to the National Cancer Database (NCDB) for sarcoma diagnoses. Methods. A retrospective analysis of a single Commission on Cancer (CoC)-accredited cancer center’s tumor registry between 2006 and 2016 identified 402 patients who underwent treatment of a musculoskeletal soft tissue sarcoma and had TTI data available. Registry-reported TTI was extracted from the tumor registry. Effective TTI was manually calculated by medical record review as the number of days from the date of tissue diagnosis to initiation of first effective treatment. Effective treatment was defined as oncologic surgical excision or initiation of radiation therapy or chemotherapy. Registry-reported TTI and effective TTI values were compared for concordance in all patients. Results. In the entire cohort, 25% (99/402) of patients had TTI data discordance, all related to surgical treatment definition. For patients with a registry-reported value of TTI = 0 days, 74% (87/118) had a diagnostic surgical procedure coded as their first treatment event, with 73 unplanned incomplete excision procedures and 14 incisional biopsies. In these patients, effective TTI was on average 59 days (P0 days, only 4% (12/284) had discordant TTI values. Conclusions. Nearly three-fourths of patients with a registry-reported value of TTI = 0 days in a large, CoC-accredited cancer center registry had a diagnostic procedure coded as their first treatment event, though their effective treatment had not yet started. These data suggest that TTI is likely longer than what is reported to the NCDB. Redefinition of what constitutes surgical treatment should be considered to improve the accuracy of data used in measuring TTI in sarcoma.

California sea cucumbers (Apostichopus californicus) are often abundant at oyster farms in British Columbia, Canada both on the suspended gear as juveniles and on the seafloor beneath them as a mixture of juveniles and adults. Their natural abundance, high value, and potential to mitigate benthic organic loading has led to an interest in their coculture with oysters. Whether farmed sea cucumbers ought to be contained to physically separate them from wild stocks is debated. The present three-year field study examined the movement of wild California sea cucumbers on/off an operational oyster farm (~3000 m2) to help inform future sea cucumber aquaculture development. Sea cucumber effects on organic loading, immigration to/emigration from the farm, and the efficacy of various containment-material mesh types and sizes were examined. Juvenile and adult sea cucumber densities on the farm steadily increased from the end of winter through the end of summer, likely due in large part to juveniles falling off the suspended oyster gear, which occurred at an average rate of ~780 ind d−1 (for the whole farm) in the summer months. The largest increase in abundance on the farm was observed between January and March/April, when the population increased by 100–350 ind d−1. Between late summer and early winter, sea cucumbers emigrated from the farm at a rate of 50–90 ind d−1, neither juvenile nor adult densities on the farm changing appreciably over the winter. The sea cucumber density showed a progressive decrease in the first 20 m from the farm, after which the animals were scarcely noticed. Apostichopus californicus did not significantly decrease sediment organics beneath the farm compared to a nearby control site, but such an effect may have been lost due to their seasonal feeding cycles and/or the presence of other benthic grazers that were not part of our exclusion trial. Overall, our findings suggest that the separation of farmed and wild California sea cucumbers on a shellfish farm can only be guaranteed through containment, given the dynamic immigration and emigration patterns of wild stocks. Through laboratory trials, we found that individuals of A. californicus were able to squeeze through mesh as small as 32% of their contracted width and could escape fenced areas (90 ± 4% escape from nylon fencing and 40 ± 8% escape from VexarTM fencing) unless the fencing extended above the water surface (where there was no escape from either type).

Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors of the immunoglobin superfamily prominently expressed by lung epithelium. Previous experiments demonstrated that over-expression of RAGE by murine alveolar epithelium throughout embryonic development causes neonatal lethality coincident with significant lung hypoplasia. In the current study, we evaluated the expression of NKX2.1 (also referred to as TTF-1), a homeodomain-containing transcription factor critical for branching morphogenesis, in mice that differentially expressed RAGE. We also contextualized NKX2.1 expression with the abundance of FoxA2, a winged double helix DNA binding protein that influences respiratory epithelial cell differentiation and surfactant protein expression. Conditional RAGE over-expression was induced in mouse lung throughout gestation (embryonic day E0–18.5), as well as during the critical saccular period of development (E15.5–18.5), and analyses were conducted at E18.5. Histology revealed markedly less lung parenchyma beginning in the canalicular stage of lung development and continuing throughout the saccular period. We discovered consistently decreased expression of both NKX2.1 and FoxA2 in lungs from transgenic (TG) mice compared to littermate controls. We also observed diminished surfactant protein C in TG mice, suggesting possible hindered differentiation and/or proliferation of alveolar epithelial cells under the genetic control of these two critical transcription factors. These results demonstrate that RAGE must be specifically regulated during lung formation. Perturbation of epithelial cell differentiation culminating in respiratory distress and perinatal lethality may coincide with elevated RAGE expression in the lung parenchyma.

Abstract This study aims to investigate the characteristics of the phenotype and management of chronic obstructive pulmonary disease (COPD) patients in the general population in China. We analyzed spirometry-confirmed COPD patients who were identified from a population-based, nationally representative sample in China. All participants were measured with airflow limitation severity based on post-bronchodilator FEV1 percent predicted, bronchodilator responsiveness, exacerbation history, and respiratory symptoms. Among a total of 9134 COPD patients, 90.3% were non-exacerbators, 2.9% were frequent exacerbators without chronic bronchitis, 2.0% were frequent exacerbators with chronic bronchitis, and 4.8% were asthma-COPD overlap. Less than 5% of non-exacerbators ever had pulmonary function testing performed. The utilization rate of inhaled medication in non-exacerbators, exacerbators without chronic bronchitis, exacerbators with chronic bronchitis, and asthma-COPD overlap was 1.4, 23.5, 29.5, and 19.4%, respectively. A comprehensive strategy for the management of COPD patients based on phenotype in primary care is urgently needed.

The Anaphase Promoting Complex (APC/C), a large cullin-RING E3-type ubiquitin ligase, constitutes the ultimate target of the Spindle Assembly Checkpoint (SAC), an intricate regulatory circuit that ensures the high fidelity of chromosome segregation in eukaryotic organisms by delaying the onset of anaphase until each chromosome is properly bi-oriented on the mitotic spindle. Cell-division cycle protein 20 homologue (CDC20) is a key regulator of APC/C function in mitosis. The formation of the APC/CCDC20 complex is required for the ubiquitination and degradation of select substrates, which is necessary to maintain the mitotic state. In contrast to the roles of CDC20 in animal species, little is known about CDC20 roles in the regulation of chromosome segregation in plants. Here we address this gap in knowledge and report the expression in insect cells; the biochemical and biophysical characterisation of Arabidopsis thaliana (AtCDC20) WD40 domain; and the nuclear and cytoplasmic distribution of full-length AtCDC20 when transiently expressed in tobacco plants. We also show that most AtCDC20 degrons share a high sequence similarity to other eukaryotes, arguing in favour of conserved degron functions in AtCDC20. However, important exceptions were noted such as the lack of a canonical MAD1 binding motif; a fully conserved RRY-box in all six AtCDC20 isoforms instead of a CRY-box motif, and low conservation of key residues known to be phosphorylated by BUB1 and PLK1 in other species to ensure a robust SAC response. Taken together, our studies provide insights into AtCDC20 structure and function and the evolution of SAC signalling in plants.

Courses are the main source of data analysis training for students. The statistical software training taught in those courses can affect student career readiness. However, lack of information about statistical software use in horticulture leads students and mentors to select statistics courses based on course availability and/or anecdotal evaluations. This research aimed to describe statistical software use trends in horticulture research to inform student course selection. We surveyed ≈50% of all articles published in HortScience, HortTechnology, and the Journal of the American Society for Horticultural Science (JASHS) between 2005 and 2020. We found that SAS, SPSS, and R were the most frequently used software packages in this period. SAS use frequency decreased in HortScience and JASHS, but not in HortTechnology. SPSS use increased in JASHS and R use increased in all journals. Results from this retrospective survey suggest that training in SAS, SPSS, and R can help align students with horticulture research practices.

Abstract Background The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression. Methods We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with and without chronic obstructive pulmonary disease (COPD) and replicated these associations in two asthma cohorts, SARP and MAST. To identify airway biology beyond ACE2 binding that may contribute to increased susceptibility, we used gene set enrichment analyses to determine if gene expression changes indicative of a suppressed airway immune response observed early in SARS-CoV-2 infection are also observed in association with host factors. To identify host genetic variants affecting COVID-19 susceptibility in SPIROMICS, we performed expression quantitative trait (eQTL) mapping and investigated the phenotypic associations of the eQTL variants. Results We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections. Conclusions These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.

Abstract Background Soluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publications have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema. No cohorts have examined the association between sRAGE and progressive decline of lung function. There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population. This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction. A meta-analysis is used to quantify sRAGE associations with clinical phenotypes. Methods sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399). We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV1) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity). Results Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P

Abstract Background There is a lack of mechanism-driven, clinically relevant biomarkers in chronic obstructive pulmonary disease (COPD). Mitochondrial dysfunction, a proposed disease mechanism in COPD, is associated with the release of mitochondrial DNA (mtDNA), but plasma cell-free mtDNA has not been previously examined prospectively for associations with clinical COPD measures. Methods P-mtDNA, defined as copy number of mitochondrially-encoded NADH dehydrogenase-1 (MT-ND1) gene, was measured by real-time quantitative PCR in 700 plasma samples from participants enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Associations between p-mtDNA and clinical disease parameters were examined, adjusting for age, sex, smoking status, and for informative loss to follow-up. Results P-mtDNA levels were higher in participants with mild or moderate COPD, compared to smokers without airflow obstruction, and to participants with severe COPD. Baseline increased p-mtDNA levels were associated with better CAT scores in female smokers without airflow obstruction and female participants with mild or moderate COPD on 1-year follow-up, but worse 6MWD in females with severe COPD. Higher p-mtDNA levels were associated with better 6MWD in male participants with severe COPD. These associations were no longer significant after adjusting for informative loss to follow-up. Conclusion In this study, p-mtDNA levels associated with baseline COPD status but not future changes in clinical COPD measures after accounting for informative loss to follow-up. To better characterize mitochondrial dysfunction as a potential COPD endotype, these results should be confirmed and validated in future studies. Trial Registration: ClinicalTrials.gov NCT01969344 (SPIROMICS)

Sweet corn is one of the most important vegetables in North America and has undergone different selection pressures than non-sweet cultivars. Here, the authors report its genome assembly and reveal the evolutionary history of modern sweet corn through population genomic analyses.

Abstract Chronic obstructive pulmonary disease (COPD) is heterogeneous in development, progression, and phenotypes. Little is known about the lung microbiome, sampled by bronchoscopy, in milder COPD and its relationships to clinical features that reflect disease heterogeneity (lung function, symptom burden, and functional impairment). Using bronchoalveolar lavage fluid collected from 181 never-smokers and ever-smokers with or without COPD (GOLD 0-2) enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS), we find that lung bacterial composition associates with several clinical features, in particular bronchodilator responsiveness, peak expiratory flow rate, and forced expiratory flow rate between 25 and 75% of FVC (FEF25–75). Measures of symptom burden (COPD Assessment Test) and functional impairment (six-minute walk distance) also associate with disparate lung microbiota composition. Drivers of these relationships include members of the Streptococcus, Prevotella, Veillonella, Staphylococcus, and Pseudomonas genera. Thus, lung microbiota differences may contribute to airway dysfunction and airway disease in milder COPD.

Abstract Introduction Pre-hospital enhanced care teams like Helicopter Emergency Medical Services (HEMS) are often dispatched to major trauma patients, including patients with traumatic brain injuries and those with major haemorrhage. For these patients, minimizing the time to definitive care is vital. The aim of this study was to determine whether increased awareness of elapsed on scene time produces a relevant time performance improvement for major trauma patients attended by HEMS, and weather introducing such a timer was feasible and acceptable to clinicians. Methods We performed a prospective cohort study of all single casualty traumatic incidents attended by Air Ambulance Kent Surrey Sussex (AAKSS) between 15 October 2016 and 23 May 2017 to test if introduction of a prompting scene timer within the service resulted in a reduction in pre-hospital scene times. Results The majority of the patients attended were male (74%) and sustained blunt trauma (92%). Overall, median scene time was 25.5 [IQR16.3] minutes before introduction of the scene timer and 23.0 [11.0] minutes after introduction, p = 0.13). Scene times for patients with a GCS

Abstract Just-in-time adaptive interventions (JITAIs), typically smartphone apps, learn to deliver therapeutic content when users need it. The challenge is to “push” content at algorithmically chosen moments without making users trigger it with effortful input. We trained a randomForest algorithm to predict heroin craving, cocaine craving, or stress (reported via smartphone app 3x/day) 90 min into the future, using 16 weeks of field data from 189 outpatients being treated for opioid-use disorder. We used only one form of continuous input (along with person-level demographic data), collected passively: an indicator of environmental exposures along the past 5 h of movement, as assessed by GPS. Our models achieved excellent overall accuracy—as high as 0.93 by the end of 16 weeks of tailoring—but this was driven mostly by correct predictions of absence. For predictions of presence, “believability” (positive predictive value, PPV) usually peaked in the high 0.70s toward the end of the 16 weeks. When the prediction target was more rare, PPV was lower. Our findings complement those of other investigators who use machine learning with more broadly based “digital phenotyping” inputs to predict or detect mental and behavioral events. When target events are comparatively subtle, like stress or drug craving, accurate detection or prediction probably needs effortful input from users, not passive monitoring alone. We discuss ways in which accuracy is difficult to achieve or even assess, and warn that high overall accuracy (including high specificity) can mask the abundance of false alarms that low PPV reveals.

In maize, starch mutants have facilitated characterization of key genes involved in endosperm starch biosynthesis such as large subunit of AGPase Shrunken2 (Sh2) and isoamylase type DBE Sugary1 (Su1). While many starch biosynthesis enzymes have been characterized, the mechanisms of certain genes (including Sugary enhancer1) are yet undefined, and very little is understood about the regulation of starch biosynthesis. As a model, we utilize commercially important sweet corn mutations, sh2 and su1, to genetically perturb starch production in the endosperm. To characterize the transcriptomic response to starch mutations and identify potential regulators of this pathway, differential expression and coexpression network analysis was performed on near-isogenic lines (NILs) (wildtype, sh2, and su1) in six genetic backgrounds. Lines were grown in field conditions and kernels were sampled in consecutive developmental stages (blister stage at 14 days after pollination (DAP), milk stage at 21 DAP, and dent stage at 28 DAP). Kernels were dissected to separate embryo and pericarp from the endosperm tissue and 3′ RNA-seq libraries were prepared. Mutation of the Su1 gene led to minimal changes in the endosperm transcriptome. Responses to loss of sh2 function include increased expression of sugar (SWEET) transporters and of genes for ABA signaling. Key regulators of starch biosynthesis and grain filling were identified. Notably, this includes Class II trehalose 6-phosphate synthases, Hexokinase1, and Apetala2 transcription factor-like (AP2/ERF) transcription factors. Additionally, our results provide insight into the mechanism of Sugary enhancer1, suggesting a potential role in regulating GA signaling via GRAS transcription factor Scarecrow-like1.

BackgroundVentriculo-arterial (VA) coupling in bicuspid aortic valve (BAV) patients can be affected by the global aortopathy characterizing BAV disease and the presence of concomitant congenital lesions such as aortic coarctation (COA). This study aimed to isolate the COA variable and use cardiovascular magnetic resonance (CMR) imaging to perform wave intensity analysis non-invasively to shed light on VA coupling changes in BAV. The primary hypothesis was that BAV patients with COA exhibit unfavorable VA coupling, and the secondary hypothesis was that BAV patients with COA exhibit increased wave speed as a marker of reduced aortic distensibility despite successful surgical correction.MethodsPatients were retrospectively identified from a CMR database and divided into two groups: isolated BAV and BAV associated with repaired COA. Aortic and ventricular dimensions, global longitudinal strain (GLS), and ascending aortic flow data and area were collected and used to derive wave intensity from CMR data. The main variables for the analysis included all wave magnitudes (forward compression/expansion waves, FCW and FEW, respectively, and reflected backward compression wave, BCW) and wave speed.ResultsIn the comparison of patients with isolated BAV and those with BAV associated with repaired COA (n = 25 in each group), no differences were observed in left ventricular ejection fraction, GLS, or ventricular volumes, whilst significant increases in FCW and FEW magnitude were noted in the BAV and repaired COA group. The FCW inversely correlated with age and aortic size. Whilst the BCW was not significantly different compared with that in patients with/without COA, its magnitude tends to increase with a lower COA index. Patients with repaired COA exhibited higher wave speed velocity. Aortic wave speed (inversely related to distensibility) was not significantly different between the two groups.ConclusionIn the absence of a significant restenosis, VA coupling in patients with BAV and COA is not negatively affected compared to patients with isolated BAV. A reduction in the magnitude of the early systolic FCW was observed in patients who were older and with larger aortic diameters.

ObjectiveBangladesh achieved the fourth Millennium Development Goal well ahead of schedule, with a significant reduction in under-5 mortality between 1990 and 2015. However, the reduction in neonatal mortality has been stagnant in recent years. The purpose of this study is to explore the association between place of delivery and newborn care with early neonatal mortality (ENNM), which represents more than 80% of total neonatal mortality in Bangladesh.MethodsIn this study, 2014 Bangladesh Demographic and Health Survey data were used to assess early neonatal survival in children born in the three years preceding the survey. The roles of place of the delivery and newborn care in ENNM were examined using multivariable logistic regression models adjusted for clustering and relevant socio-economic, pregnancy, and newborn characteristics.ResultsBetween 2012 and 2014, there were 4,624 deliveries in 17,863 sampled households, 39% of which were delivered at health facilities. The estimated early neonatal mortality rate during this period was 15 deaths per 1,000 live births. We found that newborns who had received at least 3 components of essential newborn care (ENC) were 56% less likely to die during the first seven days of their lives compared to their counterparts who received 0-2 components of ENC (aOR: 0.44; 95% CI: 0.24-0.81). In addition, newborns who had received any postnatal care (PNC) were 68% less likely to die in the early neonatal period than those who had not received any PNC (aOR: 0.32; 95% CI: 0.16-0.64). Facility delivery was not significantly associated with the risk of early newborn death in any of the models.ConclusionOur study findings highlight the importance of newborn and postnatal care in preventing early neonatal deaths. Further, findings suggest that increasing the proportion of women who give birth in a healthcare facility is not sufficient to reduce ENNM by itself; to realize the theoretical potential of facility delivery to avert neonatal deaths, we must also ensure quality of care during delivery, guarantee all components of ENC, and provide high-quality early PNC. Therefore, sustained efforts to expand access to high-quality ENC and PNC are needed in health facilities, particularly in facilities serving low-income populations.

Recent space-based missions have ushered in a new era of observational astronomy, where high-cadence photometric light curves for thousands to millions of stars in the solar neighborhood can be used to test and apply stellar age-dating methods, including gyrochronology. Combined with precise kinematics, these data allow for powerful new insights into our understanding of the Milky Way’s dynamical history. Using TESS data, we build a series of rotation period measurement and confirmation pipelines and test them on 1560 stars across five benchmark samples: the Pleiades, Pisces–Eridanus, Praesepe, the Hyades, and field stars from the MEarth Project. Our pipelines’ recovery rates across these groups are, on average, 89%. We then apply these pipelines to 4085 likely single stars with TESS light curves in two interesting regions of Galactic action space. We identify 141 unique, rapidly rotating stars in highly eccentric orbits in the disk, some of which appear as rotationally young as the 120 Myr old Pleiades. Pending spectroscopic analysis to confirm their youth, this indicates that these stars were subject to fast-acting dynamical phenomena, the origin of which will be investigated in later papers in this series.

The demographics of young exoplanets can shed light on their formation and evolution processes. Exoplanet properties are derived from the properties of their host stars. As such, it is important to accurately characterize the host stars since any systematic biases in their derivation can negatively impact the derivation of planetary properties. Here we present a uniform catalog of photometrically derived stellar effective temperatures, luminosities, radii, and masses for 4865 young (

The Tucana–Horologium association (Tuc-Hor) is a 40 Myr old moving group in the southern sky. In this work, we measure the rotation periods of 313 Tuc-Hor objects with TESS light curves derived from TESS full-frame images and membership lists driven by Gaia EDR3 kinematics and known youth indicators. We recover a period for 81.4% of the sample and report 255 rotation periods for Tuc-Hor objects. From these objects we identify 11 candidate binaries based on multiple periodic signals or outlier Gaia DR2 and EDR3 renormalized unit weight error values. We also identify three new complex rotators (rapidly rotating M dwarf objects with intricate light-curve morphology) within our sample. Along with the six previously known complex rotators that belong to Tuc-Hor, we compare their light-curve morphology between TESS Cycle 1 and Cycle 3 and find that they change substantially. Furthermore, we provide context for the entire Tuc-Hor rotation sample by describing the rotation period distributions alongside other youth indicators such as H α and Li equivalent width, as well as near-ultraviolet and X-ray flux. We find that measuring rotation periods with TESS is a fast and effective means to confirm members in young moving groups.