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The assessment of creativity as an individual difference has historically focused on divergent thinking, which is increasingly viewed as involving the associative processes that are also understood to be a key component of creative potential. Research on associative processes has proliferated in many sub-fields, often using Compound Remote Associates (CRA) tasks with an open response format and relatively small participant samples. In the present work, we introduce a new format that is more amenable to large-scale data collection in survey designs, and present evidence for the reliability and validity of CRA measures in general using multiple large samples. Study 1 uses a large, representative dataset (N = 1,323,480) to demonstrate strong unidimensionality and internal consistency (α = .97; ωt = .87), as well as links to individual differences in temperament, cognitive ability, occupation, and job characteristics. Study 2 uses an undergraduate sample (N = 685) to validate the use of a multiple-choice format relative to the traditional approach. Study 3 uses a crowdsourced sample (N = 357) to demonstrate high test-retest reliability of the items (r =.74). Finally, Study 4 uses a sample that overlaps with Study 1 (N = 1,502,922) to provide item response theory (IRT) parameters for a large set of high-quality CRA items that use a multiple-choice response mode, thus facilitating their use in future research on creativity, insight, and related topics.
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Creatividad , Humanos , Femenino , Reproducibilidad de los Resultados , Masculino , Adulto Joven , Adulto , Psicometría/métodos , Psicometría/instrumentación , Conducta de Elección/fisiología , Adolescente , Individualidad , Persona de Mediana EdadRESUMEN
There are notable parallels between processes leading to person-environment fit (PE-fit) and processes of selection and acculturation among U.S. immigrants. Thus, a natural question is: Do immigrants benefit from fitting their new environments? PE-fit appears to have uniformly positive effects in the education, career, and personality literatures, but it is unclear whether this would be the case for immigrants. The present study evaluated the PE-fit of U.S. immigrants (N = 39,195) to their new host communities (9,925 Zip Code Tabulation Areas [ZCTAs]). PE-fit varied across immigrants. On average, immigrant PE-fit was lower (b = 0.23 and b = 0.35) than the PE-fit of U.S. natives (b = 0.47; N = 122,339 from 2,374 ZCTAs). Immigrants more closely matched their community's profile when they were older, more educated, from Western countries, or from countries with French or German as the official language. PE-fit was positively associated with immigrant traits of Honesty, Introspection, Creativity, and Industry. Immigrants experienced better PE-fit when they resided in communities with more educated residents, with residents born abroad-particularly in the same world region-or with residents with a similar ethnic background. Finally, immigrant PE-fit was associated with well-being and self-reported health. We discuss the implications for the study of U.S. immigrants and the field of acculturation and propose future directions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Aculturación , Emigrantes e Inmigrantes , Humanos , Emigrantes e Inmigrantes/psicología , Estados Unidos/etnología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Medio Social , Adolescente , Anciano , Personalidad , Publicación de PreinscripciónRESUMEN
OBJECTIVE: To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association with incident CVD. RESULTS: Among 49,230 participants with T2D, 8,956 had incident CVD events (event rate 18.2%). We identified three novel genetic loci for incident CVD: rs147138607 (near CACNA1E/ZNF648, hazard ratio [HR] 1.23, P = 3.6 × 10-9), rs77142250 (near HS3ST1, HR 1.89, P = 9.9 × 10-9), and rs335407 (near TFB1M/NOX3, HR 1.25, P = 1.5 × 10-8). Among 204 known CAD loci, 5 were associated with incident CVD in T2D (multiple comparison-adjusted P < 0.00024, 0.05/204). A standardized polygenic score of these 204 variants was associated with incident CVD with HR 1.14 (P = 1.0 × 10-16). CONCLUSIONS: The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Estudio de Asociación del Genoma Completo , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Polimorfismo de Nucleótido SimpleRESUMEN
Despite their known influence in science, technology, engineering, and mathematics (STEM) fields, spatial abilities remain an underassessed aspect of cognition, particularly in educational settings. One explanation could be a lack of affordable, valid instruments for measuring various aspects of spatial ability. We evaluate the validity of a set of public-domain, algorithmically generated two-dimensional rotation items using a sample from the Synthetic Aperture Personality Assessment (SAPA) Project (N = 1,020,195). We examine the psychometric properties of the items and their relationship with various other cognitive abilities and personality traits. In addition, we identify the highest performing college majors and occupations on the 2D rotation items and on a set of 3D rotation items. Findings suggest strong unidimensionality for the 2D rotation items and the presence of lower-order factors which reflect differences across items in mental rotation demands. The highest scoring majors and occupations were similar-but not identical-across the 2D and 3D rotation measures and point to potentially meaningful differences across areas of expertise.
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BACKGROUND: Type 2 diabetes mellitus (T2D) confers a two- to three-fold increased risk of cardiovascular disease (CVD). However, the mechanisms underlying increased CVD risk among people with T2D are only partially understood. We hypothesized that a genetic association study among people with T2D at risk for developing incident cardiovascular complications could provide insights into molecular genetic aspects underlying CVD. METHODS: From 16 studies of the Cohorts for Heart & Aging Research in Genomic Epidemiology (CHARGE) Consortium, we conducted a multi-ancestry time-to-event genome-wide association study (GWAS) for incident CVD among people with T2D using Cox proportional hazards models. Incident CVD was defined based on a composite of coronary artery disease (CAD), stroke, and cardiovascular death that occurred at least one year after the diagnosis of T2D. Cohort-level estimated effect sizes were combined using inverse variance weighted fixed effects meta-analysis. We also tested 204 known CAD variants for association with incident CVD among patients with T2D. RESULTS: A total of 49,230 participants with T2D were included in the analyses (31,118 European ancestries and 18,112 non-European ancestries) which consisted of 8,956 incident CVD cases over a range of mean follow-up duration between 3.2 and 33.7 years (event rate 18.2%). We identified three novel, distinct genetic loci for incident CVD among individuals with T2D that reached the threshold for genome-wide significance (P<5.0×10-8): rs147138607 (intergenic variant between CACNA1E and ZNF648) with a hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.15 - 1.32, P=3.6×10-9, rs11444867 (intergenic variant near HS3ST1) with HR 1.89, 95% CI 1.52 - 2.35, P=9.9×10-9, and rs335407 (intergenic variant between TFB1M and NOX3) HR 1.25, 95% CI 1.16 - 1.35, P=1.5×10-8. Among 204 known CAD loci, 32 were associated with incident CVD in people with T2D with P<0.05, and 5 were significant after Bonferroni correction (P<0.00024, 0.05/204). A polygenic score of these 204 variants was significantly associated with incident CVD with HR 1.14 (95% CI 1.12 - 1.16) per 1 standard deviation increase (P=1.0×10-16). CONCLUSIONS: The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.
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Some people use health care services more than others. Identifying factors associated with health care use has the potential to improve the effectiveness, efficiency, and equity of health care. In line with the Andersen behavioral model of health care utilization and initial empirical findings, personality traits may be key predisposing factors associated with health care use. Across 15 samples, the present study examined cross-sectional and prospective associations between Big Five personality traits and the likelihood of dental visits, general medical practitioner visits, and hospitalizations. Using coordinated data analysis, we estimated models within each of 15 samples individually (sample Ns ranged from 516 to 305,762), and then calculated weighted mean effect sizes using random-effects meta-analysis across samples (total N = 358,803). According to the synthesized results, people higher in conscientiousness, agreeableness, extraversion, and openness, and lower in neuroticism were more likely to visit the dentist; people higher in neuroticism were more likely to visit general medical practitioners; and people lower in conscientiousness and agreeableness and higher in neuroticism were more likely to be hospitalized. Associations tended to be small with odds ratios around 1.20 (rs ≈ .05). These findings provide evidence across 15 international samples for small but consistent associations between personality traits and health care use and demonstrate that personality-health care associations differ by type of care. We discuss directions for future research, including examining more specific personality facets (e.g., productiveness vs. responsibility) as well as important dimensions of health care (e.g., preventative vs. reactive care; acute vs. chronic care). (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Trastornos de la Personalidad , Personalidad , Humanos , Estudios Transversales , Neuroticismo , Atención a la SaludRESUMEN
INTRODUCTION: Pulmonary arterial hypertension (PAH) is characterised by loss of microvessels. The Wnt pathways control pulmonary angiogenesis but their role in PAH is incompletely understood. We hypothesised that Wnt activation in pulmonary microvascular endothelial cells (PMVECs) is required for pulmonary angiogenesis, and its loss contributes to PAH. METHODS: Lung tissue and PMVECs from healthy and PAH patients were screened for Wnt production. Global and endothelial-specific Wnt7a -/- mice were generated and exposed to chronic hypoxia and Sugen-hypoxia (SuHx). RESULTS: Healthy PMVECs demonstrated >6-fold Wnt7a expression during angiogenesis that was absent in PAH PMVECs and lungs. Wnt7a expression correlated with the formation of tip cells, a migratory endothelial phenotype critical for angiogenesis. PAH PMVECs demonstrated reduced vascular endothelial growth factor (VEGF)-induced tip cell formation as evidenced by reduced filopodia formation and motility, which was partially rescued by recombinant Wnt7a. We discovered that Wnt7a promotes VEGF signalling by facilitating Y1175 tyrosine phosphorylation in vascular endothelial growth factor receptor 2 (VEGFR2) through receptor tyrosine kinase-like orphan receptor 2 (ROR2), a Wnt-specific receptor. We found that ROR2 knockdown mimics Wnt7a insufficiency and prevents recovery of tip cell formation with Wnt7a stimulation. While there was no difference between wild-type and endothelial-specific Wnt7a -/- mice under either chronic hypoxia or SuHx, global Wnt7a +/- mice in hypoxia demonstrated higher pulmonary pressures and severe right ventricular and lung vascular remodelling. Similar to PAH, Wnt7a +/- PMVECs exhibited an insufficient angiogenic response to VEGF-A that improved with Wnt7a. CONCLUSIONS: Wnt7a promotes VEGF signalling in lung PMVECs and its loss is associated with an insufficient VEGF-A angiogenic response. We propose that Wnt7a deficiency contributes to progressive small vessel loss in PAH.
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Hipertensión Arterial Pulmonar , Ratones , Animales , Hipertensión Arterial Pulmonar/complicaciones , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Endoteliales/metabolismo , Hipertensión Pulmonar Primaria Familiar/metabolismo , Hipoxia/metabolismoRESUMEN
Recent advances in natural language processing (NLP) have produced general models that can perform complex tasks such as summarizing long passages and translating across languages. Here, we introduce a method to extract adjective similarities from language models as done with survey-based ratings in traditional psycholexical studies but using millions of times more text in a natural setting. The correlational structure produced through this method is highly similar to that of self- and other-ratings of 435 English terms reported by Saucier and Goldberg (1996a). The first three unrotated factors produced using NLP are congruent with those in survey data, with coefficients of 0.89, 0.79, and 0.79. This structure is robust to many modeling decisions: adjective set, including those with 1,710 (Goldberg, 1982) and 18,000 English terms (Allport & Odbert, 1936); the query used to extract correlations; and language model. Notably, Neuroticism and Openness are only weakly and inconsistently recovered. This is a new source of signal that is closer to the original (semantic) vision of the lexical hypothesis. The method can be applied where surveys cannot: in dozens of languages simultaneously, with tens of thousands of items, on historical text, and at extremely large scale for little cost. The code is made public to facilitate reproduction and fast iteration in new directions of research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Lenguaje , Semántica , Humanos , Personalidad , Trastornos de la Personalidad , NeuroticismoRESUMEN
BACKGROUND: Clinical use of genotype data requires high positive predictive value (PPV) and thorough understanding of the genotyping platform characteristics. BeadChip arrays, such as the Global Screening Array (GSA), potentially offer a high-throughput, low-cost clinical screen for known variants. We hypothesize that quality assessment and comparison to whole-genome sequence and benchmark data establish the analytical validity of GSA genotyping. METHODS: To test this hypothesis, we selected 263 samples from Coriell, generated GSA genotypes in triplicate, generated whole genome sequence (rWGS) genotypes, assessed the quality of each set of genotypes, and compared each set of genotypes to each other and to the 1000 Genomes Phase 3 (1KG) genotypes, a performance benchmark. For 59 genes (MAP59), we also performed theoretical and empirical evaluation of variants deemed medically actionable predispositions. RESULTS: Quality analyses detected sample contamination and increased assay failure along the chip margins. Comparison to benchmark data demonstrated that > 82% of the GSA assays had a PPV of 1. GSA assays targeting transitions, genomic regions of high complexity, and common variants performed better than those targeting transversions, regions of low complexity, and rare variants. Comparison of GSA data to rWGS and 1KG data showed > 99% performance across all measured parameters. Consistent with predictions from prior studies, the GSA detection of variation within the MAP59 genes was 3/261. CONCLUSION: We establish the analytical validity of GSA assays using quality analytics and comparison to benchmark and rWGS data. GSA assays meet the standards of a clinical screen although assays interrogating rare variants, transversions, and variants within low-complexity regions require careful evaluation.
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Benchmarking , Secuenciación de Nucleótidos de Alto Rendimiento , Genoma , Genotipo , Polimorfismo de Nucleótido SimpleRESUMEN
The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirically and quantitatively derived dimensional classification system designed to describe the features of psychopathology and, ultimately, to replace categorical nosologies. Among the constructs that HiTOP organizes are "symptom components" and "maladaptive traits," but past HiTOP publications have not fully explicated the distinction between symptoms and traits. We propose working definitions of symptoms and traits and explore challenges, exceptions, and remaining questions. Specifically, we propose that the only systematic difference between symptoms and traits in HiTOP is one of time frame. Maladaptive traits are dispositional constructs that describe persistent tendencies to manifest features of psychopathology, whereas symptoms are features of psychopathology as they are manifest during any specific time period (from moments to days to months). This has the consequence that almost every HiTOP dimension, at any level of the hierarchy, can be assessed as either a trait or a symptom dimension, by adjusting the framing of the assessment. We discuss the implications of these definitions for causal models of the relations between symptoms and traits and for distinctions between psychopathology, normal personality variation, and dysfunction.
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Trastornos de la Personalidad , Psicopatología , Humanos , Personalidad , Trastornos de la Personalidad/diagnóstico , Inventario de PersonalidadRESUMEN
Pulmonary arterial hypertension (PAH) is a rare disease associated with abnormally elevated pulmonary pressures and right heart failure resulting in high morbidity and mortality. Although the prognosis for patients with PAH has improved with the introduction of pulmonary vasodilators, disease progression remains a major problem. Given that available therapies are inadequate for preventing small-vessel loss and obstruction, there is active interest in identifying drugs capable of targeting angiogenesis and mechanisms involved in the regulation of cell growth and fibrosis. Among the mechanisms linked to PAH pathogenesis, preclinical studies have identified promising compounds that are currently being tested in clinical trials. These drugs target seven of the major mechanisms associated with PAH pathogenesis: bone morphogenetic protein signaling, tyrosine kinase receptors, estrogen metabolism, extracellular matrix, angiogenesis, epigenetics, and serotonin metabolism. In this review, we discuss the preclinical studies that led to prioritization of these mechanisms, and discuss completed and ongoing phase 2/3 trials using novel interventions such as sotatercept, anastrozole, rodatristat ethyl, tyrosine kinase inhibitors, and endothelial progenitor cells, among others. We anticipate that the next generation of compounds will build on the success of the current standard of care and improve clinical outcomes and quality of life for patients with PAH.
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Insuficiencia Cardíaca , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Hipertensión Pulmonar Primaria Familiar/complicaciones , Insuficiencia Cardíaca/complicaciones , Humanos , Calidad de VidaRESUMEN
BACKGROUND: Identifying the factors that predict non-adherence to recommended preventive pediatric care is necessary for the development of successful interventions to improve compliance. PURPOSE: Given the substantial decline in well-child visits and influenza vaccinations, we sought to examine sociodemographic (i.e., parent age, education, employment status, child age, insurance coverage, household size, race and ethnicity, income, COVID-19 incidence in state) and psychosocial (i.e., child temperament, parent mental health, parent personality traits) factors associated with preventative pediatric care (well-child visits, influenza vaccines) during the COVID-19 pandemic. METHODS: As part of a larger, ongoing study, 1875 parents (96% mothers, 65% age 35 or younger, 58% with a college degree) reported whether they had missed any recommended or scheduled well-child visits since the pandemic and whether they had vaccinated their child against the flu. Using data collected during fall 2020, we examine differences in these health outcomes across social/demographic factors and psychological profiles. In addition, we use lasso logistic regression models to (1) estimate the accuracy with which we can predict adherence from these characteristics and (2) identify factors most strongly, independently associated with adherence. RESULTS: Parent psychological factors were associated with outcomes above and beyond known demographic and social factors. For example, parent industriousness and orderliness were associated with greater likelihoods of attending well-child visits and vaccinating children, while parent conservatism and creativity were associated with lower rates. We also replicate prior work documenting that health insurance, income, and household size are major factors in receiving adequate pediatric care. CONCLUSIONS: Adherence to preventive pediatric care varies as a function of psychological factors, suggesting that the current system of pediatric care favors some psychological profiles over others. However, the specific traits associated with non-adherence point to potentially fruitful interventions, specifically around increasing functional proximity.
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COVID-19 , Pandemias , Adulto , Niño , Femenino , Humanos , Seguro de Salud , Madres , Pandemias/prevención & control , SARS-CoV-2RESUMEN
Pericytes are mesenchymal-derived mural cells localized within the basement membrane of pulmonary and systemic capillaries. Besides structural support, pericytes control vascular tone, produce extracellular matrix components, and cytokines responsible for promoting vascular homeostasis and angiogenesis. However, pericytes can also contribute to vascular pathology through the production of pro-inflammatory and pro-fibrotic cytokines, differentiation into myofibroblast-like cells, destruction of the extracellular matrix, and dissociation from the vessel wall. In the lung, pericytes are responsible for maintaining the integrity of the alveolar-capillary membrane and coordinating vascular repair in response to injury. Loss of pericyte communication with alveolar capillaries and a switch to a pro-inflammatory/pro-fibrotic phenotype are common features of lung disorders associated with vascular remodeling, inflammation, and fibrosis. In this article, we will address how to differentiate pericytes from other cells, discuss the molecular mechanisms that regulate the interactions of pericytes and endothelial cells in the pulmonary circulation, and the experimental tools currently used to study pericyte biology both in vivo and in vitro. We will also discuss evidence that links pericytes to the pathogenesis of clinically relevant lung disorders such as pulmonary hypertension, idiopathic lung fibrosis, sepsis, and SARS-COVID. Future studies dissecting the complex interactions of pericytes with other pulmonary cell populations will likely reveal critical insights into the origin of pulmonary diseases and offer opportunities to develop novel therapeutics to treat patients afflicted with these devastating disorders. © 2021 American Physiological Society. Compr Physiol 11:2227-2247, 2021.
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COVID-19 , Pericitos , Células Endoteliales , Humanos , Pulmón , SARS-CoV-2RESUMEN
Background: Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary vascular remodeling and right heart failure. Specific genetic variants increase the incidence of PAH in carriers with a family history of PAH, those who suffer from certain medical conditions, and even those with no apparent risk factors. Inflammation and immune dysregulation are related to vascular remodeling in PAH, but whether genetic susceptibility modifies the PAH immune response is unclear. TNIP2 and TRAF2 encode for immunomodulatory proteins that regulate NF-κB activation, a transcription factor complex associated with inflammation and vascular remodeling in PAH. Methods: Two unrelated families with PAH cases underwent whole-exome sequencing (WES). A custom pipeline for variant prioritization was carried out to obtain candidate variants. To determine the impact of TNIP2 and TRAF2 in cell proliferation, we performed an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay on healthy lung pericytes transfected with siRNA specific for each gene. To measure the effect of loss of TNIP2 and TRAF2 on NF-kappa-beta (NF-κB) activity, we measured levels of Phospho-p65-NF-κB in siRNA-transfected pericytes using western immunoblotting. Results: We discovered a novel missense variant in the TNIP2 gene in two affected individuals from the same family. The two patients had a complex form of PAH with interatrial communication and scleroderma. In the second family, WES of the proband with PAH and primary biliary cirrhosis revealed a de novo protein-truncating variant in the TRAF2. The knockdown of TNIP2 and TRAF2 increased NF-κB activity in healthy lung pericytes, which correlated with a significant increase in proliferation over 24 h. Conclusions: We have identified two rare novel variants in TNIP2 and TRAF2 using WES. We speculate that loss of function in these genes promotes pulmonary vascular remodeling by allowing overactivation of the NF-κB signaling activity. Our findings support a role for WES in helping identify novel genetic variants associated with dysfunctional immune response in PAH.
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Personality traits are important predictors of health behaviors, healthcare utilization, and health outcomes. However, we know little about the role of personality traits for emergency department outcomes. The present study used data from 200 patients (effective Ns range from 84 to 191), who were being discharged from the emergency department at an urban hospital, to investigate whether the Big Five personality traits were associated with post-discharge outcomes (i.e., filling prescriptions, following up with primary care physician, making an unscheduled return to the emergency department). Using logistic regression, we found few associations among the broad Big Five domains and post-discharge outcomes. However, results showed statistically significant associations between specific Big Five items (e.g., "responsible") and the three post-discharge outcomes. This study demonstrates the feasibility of assessing personality traits in an emergency medicine setting and highlights the utility of having information about patients' personality tendencies for predicting post-discharge compliance.
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Personality is not the most popular subfield of psychology. But, in one way or another, personality psychologists have played an outsized role in the ongoing "credibility revolution" in psychology. Not only have individual personality psychologists taken on visible roles in the movement, but our field's practices and norms have now become models for other fields to emulate (or, for those who share Baumeister's (2016, https://doi.org/10.1016/j.jesp.2016.02.003) skeptical view of the consequences of increasing rigor, a model for what to avoid). In this article we discuss some unique features of our field that may have placed us in an ideal position to be leaders in this movement. We do so from a subjective perspective, describing our impressions and opinions about possible explanations for personality psychology's disproportionate role in the credibility revolution. We also discuss some ways in which personality psychology remains less-than-optimal, and how we can address these flaws.
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The delicate structure of murine lungs poses many challenges for acquiring high-quality images that truly represent the living lung. Here, we describe several optimized procedures for obtaining and imaging murine lung tissue. Compared to traditional paraffin cross-section and optimal cutting temperature (OCT), agarose-inflated vibratome sections (aka precision-cut lung slices), combines comparable structural preservation with experimental flexibility. In particular, we discuss an optimized procedure to precision-cut lung slices that can be used to visualize three-dimensional cell-cell interactions beyond the limitations of two-dimensional imaging. Super-resolution microscopy can then be used to reveal the fine structure of lung tissue's cellular bodies and processes that regular confocal cannot. Lastly, we evaluate the entire lung vasculature with clearing technology that allows imaging of the entire volume of the lung without sectioning. In this manuscript, we combine the above procedures to create a novel and evolutionary method to study cell behavior ex vivo, trace and reconstruct pulmonary vasculature, address fundamental questions relevant to a wide variety of vascular disorders, and perceive implications to better imaging clinical tissue.
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CONTEXT: Gestational diabetes (GDM) has profound effects on the intrauterine metabolic milieu and is linked to obesity and diabetes in offspring, but the mechanisms driving these effects remain largely unknown. Alterations in DNA methylation and gene expression in amniocytes exposed to GDM in utero represent a potential mechanism leading to metabolic dysfunction later in life. OBJECTIVE: To profile changes in genome-wide DNA methylation and expression in human amniocytes exposed to GDM. DESIGN: A nested case-control study (n = 14 pairs) was performed in amniocytes matched for offspring sex, maternal race/ethnicity, maternal age, gestational age at amniocentesis, and gestational age at birth. Sex-specific genome-wide DNA methylation analysis and RNA-sequencing were completed and differentially methylated regions (DMRs) and gene expression changes were identified. Ingenuity pathway analysis identified biologically relevant pathways enriched after GDM exposure. In silico high-throughput chromosome conformation capture (Hi-C) analysis identified potential chromatin interactions with DMRs. RESULTS: Expression of interferon-stimulated genes was increased in GDM amniocytes, accounting for 6 of the top 10 altered genes (q < 0.05). Enriched biological pathways in GDM amniocytes included pathways involving inflammation, the interferon response, fatty liver disease, monogenic diabetes, and atherosclerosis. Forty-two DMRs were identified in male GDM-exposed amniocytes and 20 in female amniocyte analysis (q < 0.05). Hi-C analysis identified interactions between DMRs and 11 genes with significant expression changes in male amniocytes and 9 in female amniocytes (P < .05). CONCLUSION: In a unique repository of human amniocytes exposed to GDM in utero, transcriptome analysis identified enrichment of inflammation and interferon-related pathways and novel DMRs with potential distal regulatory functions.