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1.
Magn Reson Med ; 91(5): 1978-1993, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38102776

RESUMO

PURPOSE: To propose a new reconstruction method for multidimensional MR fingerprinting (mdMRF) to address shading artifacts caused by physiological motion-induced measurement errors without navigating or gating. METHODS: The proposed method comprises two procedures: self-calibration and subspace reconstruction. The first procedure (self-calibration) applies temporally local matrix completion to reconstruct low-resolution images from a subset of under-sampled data extracted from the k-space center. The second procedure (subspace reconstruction) utilizes temporally global subspace reconstruction with pre-estimated temporal subspace from low-resolution images to reconstruct aliasing-free, high-resolution, and time-resolved images. After reconstruction, a customized outlier detection algorithm was employed to automatically detect and remove images corrupted by measurement errors. Feasibility, robustness, and scan efficiency were evaluated through in vivo human brain imaging experiments. RESULTS: The proposed method successfully reconstructed aliasing-free, high-resolution, and time-resolved images, where the measurement errors were accurately represented. The corrupted images were automatically and robustly detected and removed. Artifact-free T1, T2, and ADC maps were generated simultaneously. The proposed reconstruction method demonstrated robustness across different scanners, parameter settings, and subjects. A high scan efficiency of less than 20 s per slice has been achieved. CONCLUSION: The proposed reconstruction method can effectively alleviate shading artifacts caused by physiological motion-induced measurement errors. It enables simultaneous and artifact-free quantification of T1, T2, and ADC using mdMRF scans without prospective gating, with robustness and high scan efficiency.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Algoritmos , Imagens de Fantasmas , Artefatos
2.
Magn Reson Med ; 91(5): 2074-2088, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38192239

RESUMO

PURPOSE: Quantitative MRI techniques such as MR fingerprinting (MRF) promise more objective and comparable measurements of tissue properties at the point-of-care than weighted imaging. However, few direct cross-modal comparisons of MRF's repeatability and reproducibility versus weighted acquisitions have been performed. This work proposes a novel fully automated pipeline for quantitatively comparing cross-modal imaging performance in vivo via atlas-based sampling. METHODS: We acquire whole-brain 3D-MRF, turbo spin echo, and MPRAGE sequences three times each on two scanners across 10 subjects, for a total of 60 multimodal datasets. The proposed automated registration and analysis pipeline uses linear and nonlinear registration to align all qualitative and quantitative DICOM stacks to Montreal Neurological Institute (MNI) 152 space, then samples each dataset's native space through transformation inversion to compare performance within atlas regions across subjects, scanners, and repetitions. RESULTS: Voxel values within MRF-derived maps were found to be more repeatable (σT1 = 1.90, σT2 = 3.20) across sessions than vendor-reconstructed MPRAGE (σT1w = 6.04) or turbo spin echo (σT2w = 5.66) images. Additionally, MRF was found to be more reproducible across scanners (σT1 = 2.21, σT2 = 3.89) than either qualitative modality (σT1w = 7.84, σT2w = 7.76). Notably, differences between repeatability and reproducibility of in vivo MRF were insignificant, unlike the weighted images. CONCLUSION: MRF data from many sessions and scanners can potentially be treated as a single dataset for harmonized analysis or longitudinal comparisons without the additional regularization steps needed for qualitative modalities.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Humanos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Imagens de Fantasmas , Processamento de Imagem Assistida por Computador/métodos
3.
J Magn Reson Imaging ; 59(5): 1758-1768, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37515516

RESUMO

PURPOSE: To explore whether MR fingerprinting (MRF) scans provide motion-robust and quantitative brain tissue measurements for non-sedated infants with prenatal opioid exposure (POE). STUDY TYPE: Prospective. POPULATION: 13 infants with POE (3 male; 12 newborns (age 7-65 days) and 1 infant aged 9-months). FIELD STRENGTH/SEQUENCE: 3T, 3D T1-weighted MPRAGE, 3D T2-weighted TSE and MRF sequences. ASSESSMENT: The image quality of MRF and MRI was assessed in a fully crossed, multiple-reader, multiple-case study. Sixteen image quality features in three types-image artifacts, structure and myelination visualization-were ranked by four neuroradiologists (8, 7, 5, and 8 years of experience respectively), using a 3-point scale. MRF T1 and T2 values in 8 white matter brain regions were compared between babies younger than 1 month and babies between 1 and 2 months. STATISTICAL TESTS: Generalized estimating equations model to test the significance of differences of regional T1 and T2 values of babies under 1 month and those older. MRI and MRF image quality was assessed using Gwet's second order auto-correlation coefficient (AC2) with confidence levels. The Cochran-Mantel-Haenszel test was used to assess the difference in proportions between MRF and MRI for all features and stratified by the type of features. A P value <0.05 was considered statistically significant. RESULTS: The MRF of two infants were excluded in T1 and T2 value analysis due to severe motion artifact but were included in the image quality assessment. In infants under 1 month of age (N = 6), the T1 and T2 values were significantly higher compared to those between 1 and 2 months of age (N = 4). MRF images showed significantly higher image quality ratings in all three feature types compared to MRI images. CONCLUSIONS: MR Fingerprinting scans have potential to be a motion-robust and efficient method for nonsedated infants. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.


Assuntos
Analgésicos Opioides , Processamento de Imagem Assistida por Computador , Recém-Nascido , Humanos , Masculino , Processamento de Imagem Assistida por Computador/métodos , Estudos Prospectivos , Imagens de Fantasmas , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
4.
MAGMA ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39414686

RESUMO

Standard quantitative abdominal MRI techniques are time consuming, require breath-holds, and are susceptible to patient motion artifacts. Magnetic resonance fingerprinting (MRF) is naturally multi-parametric and quantifies multiple tissue properties, including T1 and T2. This work includes T2* and off-resonance mapping into a free-breathing MRF framework utilizing a pilot tone navigator. The new acquisition and reconstruction are compared to current clinical standards. Prospective. Ten volunteers. 3 T scanner, Quadratic-RF MRF, Balanced SSFP, Inversion recovery spin-echo, LiverLab. MRI ROIs were evaluated in the liver, spleen, pancreas, kidney (cortex and medulla), and paravertebral muscle by two abdominal imaging investigators for ten healthy adult volunteers for clinical standard, breath-Hold (BH) qRF-MRF, and free-breathing qRF-MRF with pilot-tone (PT) acquisitions. Bland-Altman analysis as well as Student's T tests were used to evaluate and compare the respective ROI analyses. Quantitative values between breath-Hold (BH) and free-breathing qRF-MRF with pilot-tone (PT) results show good agreement with clinical standard T1 and T2 quantitative mapping, and Dixon q-VIBE (acquired using the Siemens LiverLAB). In this work, we show free-breathing abdominal MRF (T1, T2) with T2* results that are quantitatively comparable to current breath-hold MRF and clinical techniques.

5.
J Pers ; 92(3): 653-665, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38450583

RESUMO

People vary in how they perceive, think about, and respond to moral issues. Clearly, we cannot fully understand the psychology of morality without accounting for individual differences in moral functioning. But decades of neglect of and explicit skepticism toward such individual differences has resulted in a lack of integration between moral psychology and personality psychology-the study of psychological differences between people. In recent years, these barriers to progress have started to break down. This special issue aims to celebrate and further increase the visibility of the personality psychology of morality. Here, we introduce the articles in this special issue by highlighting some important contributions a personality-based perspective has to offer moral psychology-particularly in comparison to the currently prominent social psychological approach. We show that personality psychology is well-placed to (a) contribute toward a rigorous empirical foundation for moral psychology, (b) tackle the conceptualization and assessment of stable moral tendencies, (c) assess the predictive validity of moral traits in relation to consequential outcomes, (d) uncover the mechanisms underlying individual differences in moral judgments and behavior, and (e) provide insights into moral development. For these reasons, we believe that moral psychology needs personality psychology to reach its full scholarly potential.


Assuntos
Princípios Morais , Personalidade , Humanos , Individualidade , Julgamento
6.
J Pers ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38014735

RESUMO

OBJECTIVE: The psychological profile of the moral person might depend on whose perspective is being used. Here, we decompose moral impressions into three components: (a) Shared Moral Character (shared variance across self- and informant reports), (b) Moral Identity (how a person uniquely views their morality), and (c) Moral Reputation (how others uniquely view that person's morality). METHOD: In two samples (total N = 458), we used an extended version of the Trait-Reputation-Identity model to examine the extent to which each perspective accounts for the overall variance in moral impressions and the degree to which social and personal outcomes were associated with each perspective, controlling for method variance (i.e., positivity and acquiescence bias). RESULTS: Results suggest that moral character impressions are strongly influenced by positivity and largely idiosyncratic. All components were related to higher levels of agreeableness. For the most part, however, the three components had unique correlates: people higher in Shared Moral Character tended to have higher standings on conscientiousness and honesty-humility, were more respected, and donated more during an in-lab game; people higher in Moral Identity endorsed various moral foundations to a greater extent; and people higher in Moral Reputation valued the loyalty foundation less. CONCLUSION: These results demonstrate the value of considering multiple perspectives when measuring moral character.

7.
J Pers ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652292

RESUMO

OBJECTIVE: What types of moral improvements do people wish to make? Do they hope to become more good, or less bad? Do they wish to be more caring? More honest? More loyal? And why exactly do they want to become more moral? Presumably, most people want to improve their morality because this would benefit others, but is this in fact their primary motivation? Here, we begin to investigate these questions. METHOD: Across two large, preregistered studies (N = 1818), participants provided open-ended descriptions of one change they could make in order to become more moral; they then reported their beliefs about and motives for this change. RESULTS: In both studies, people most frequently expressed desires to improve their compassion and more often framed their moral improvement goals in terms of amplifying good behaviors than curbing bad ones. The strongest predictor of moral motivation was the extent to which people believed that making the change would have positive consequences for their own well-being. CONCLUSIONS: Together, these studies provide rich descriptive insights into how ordinary people want to be more moral, and show that they are particularly motivated to do so for their own sake.

8.
Psychol Sci ; 31(3): 243-257, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32045329

RESUMO

Most people want to change some aspects of their personality, but does this phenomenon extend to moral character and to close others? Targets (n = 800) rated their personality traits and reported how much they wanted to change on each trait; well-acquainted informants (n = 958) rated targets' personality traits and how much they wanted the targets to change on those same traits. Targets and informants reported a lower desire to change more morally relevant traits (e.g., honesty, compassion, fairness) compared with less morally relevant traits (e.g., anxiety, sociability, productiveness)-even after we controlled for current trait levels. Moreover, although targets generally wanted to improve more on traits that they had less desirable levels of, and informants wanted their targets to improve more on those traits as well, targets' moral change goals were less calibrated to their current trait levels. Finally, informants wanted targets to change in similar ways, but to a lesser extent, than targets themselves did. These findings suggest that moral considerations take a back seat when it comes to self-improvement.


Assuntos
Caráter , Princípios Morais , Autoimagem , Percepção Social , Adolescente , Adulto , Família/psicologia , Feminino , Amigos/psicologia , Humanos , Julgamento , Masculino , Inquéritos e Questionários , Adulto Jovem
9.
Psychol Sci ; 30(3): 405-414, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30653411

RESUMO

Knowing yourself requires knowing not only what you are like in general (trait self-knowledge) but also how your personality fluctuates from moment to moment (state self-knowledge). We examined this latter form of self-knowledge. Participants (248 people; 2,938 observations) wore the Electronically Activated Recorder (EAR), an unobtrusive audio recorder, and completed experience-sampling self-reports of their personality states four times each day for 1 week. We estimated state self-knowledge by comparing self-reported personality states with consensual observer ratings of personality states coded from the EAR files, which formed the criterion for what participants were "actually" like in the moment. People had self-insight into their momentary extraversion, conscientiousness, and likely neuroticism, suggesting that people can accurately detect fluctuations in some aspects of their personality. However, the evidence for self-insight was weaker for agreeableness. This apparent self-ignorance may be partly responsible for interpersonal problems and for blind spots in trait self-knowledge.


Assuntos
Avaliação Momentânea Ecológica/estatística & dados numéricos , Emoções/fisiologia , Neuroticismo/fisiologia , Personalidade/fisiologia , Adolescente , Adulto , Extroversão Psicológica , Feminino , Humanos , Relações Interpessoais , Conhecimento , Masculino , Autoimagem , Autorrelato , Comportamento Social , Estudantes/psicologia , Adulto Jovem
10.
J Pers ; 86(2): 158-172, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28035671

RESUMO

OBJECTIVE: Personality traits are associated with well-being, but the precise correlates vary across well-being dimensions and within each Big Five domain. This study is the first to examine the unique associations between the Big Five aspects (rather than facets) and multiple well-being dimensions. METHOD: Two samples of U.S. participants (total N = 706; Mage = 36.17; 54% female) recruited via Amazon's Mechanical Turk completed measures of the Big Five aspects and subjective, psychological, and PERMA well-being. RESULTS: One aspect within each domain was more strongly associated with well-being variables. Enthusiasm and Withdrawal were strongly associated with a broad range of well-being variables, but other aspects of personality also had idiosyncratic associations with distinct forms of positive functioning (e.g., Compassion with positive relationships, Industriousness with accomplishment, and Intellect with personal growth). CONCLUSIONS: An aspect-level analysis provides an optimal (i.e., parsimonious yet sufficiently comprehensive) framework for describing the relation between personality traits and multiple ways of thriving in life.


Assuntos
Satisfação Pessoal , Personalidade , Adolescente , Adulto , Idoso , Emoções , Empatia , Feminino , Felicidade , Humanos , Masculino , Pessoa de Meia-Idade , Isolamento Social , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
11.
J Am Chem Soc ; 139(9): 3312-3315, 2017 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-28121424

RESUMO

Covalent conjugation of water-soluble polymers to proteins is critical for evading immune surveillance in the field of biopharmaceuticals. The most common and long-standing polymer modification is the attachment of methoxypoly(ethylene glycol) (mPEG), termed PEGylation, which has led to several clinically approved pharmaceuticals. Recent data indicate that brush-type polymers significantly enhance in vitro and in vivo properties. Herein, the polymer conformation of poly(ethylene glycol) is detailed and compared with those of water-soluble polyacrylate and polynorbornene (PNB) when attached to icosahedral virus-like particles. Small-angle neutron scattering reveals vastly different polymer conformations of the multivalent conjugates. Immune recognition of conjugated particles was evaluated versus PEGylated particles, and PNB conjugation demonstrated the most effective shielding from antibody recognition.


Assuntos
Acrilatos/química , Plásticos/química , Polietilenoglicóis/química , Vacinas de Partículas Semelhantes a Vírus/química , Animais , Camundongos , Modelos Moleculares , Estrutura Molecular , Difração de Nêutrons , Espalhamento a Baixo Ângulo
12.
ChemSusChem ; 17(18): e202400238, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-38609332

RESUMO

The hydrogenolysis of polymers is emerging as a promising approach to deconstruct plastic waste into valuable chemicals. Yet, the complexity of plastic waste, including multilayer packaging, is a significant barrier to handling realistic waste streams. Herein, we reveal fundamental insights into a new chemical route for transforming a previously unaddressed fraction of plastic waste - poly(ethylene-co-vinyl alcohol) (EVOH) and related polymer blends - into alkane products. We report that Ru/ZrO2 is active for the concurrent hydrogenolysis, hydrogenation, and hydrodeoxygenation of EVOH and its thermal degradation products into alkanes (C1-C35) and water. Detailed reaction data, product analysis, and catalyst characterization reveal that the in-situ thermal degradation of EVOH forms aromatic intermediates that are detrimental to catalytic activity. Increased hydrogen pressure promotes hydrogenation of these aromatics, preventing catalyst deactivation and improving alkane product yields. Calculated apparent rates of C-C scission reveal that the hydrogenolysis of EVOH is slower than low-density polyethylene. We apply these findings to achieve hydrogenolysis of EVOH/polyethylene blends and elucidate the sensitivity of hydrogenolysis catalysts to such blends. Overall, we demonstrate progress towards efficient catalytic processes for the hydroconversion of waste multilayer film plastic packaging into valuable products.

13.
AJNR Am J Neuroradiol ; 45(9): 1299-1307, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-38684319

RESUMO

BACKGROUND AND PURPOSE: Understanding sex-based differences in patients with glioblastoma is necessary for accurate personalized treatment planning to improve patient outcomes. Our purpose was to investigate sex-specific differences in molecular, clinical, and radiologic tumor parameters, as well as survival outcomes in patients with glioblastoma, isocitrate dehydrogenase-1 wild-type (IDH1-WT), grade 4. MATERIALS AND METHODS: Retrospective data of 1832 patients with glioblastoma, IDH1-WT with comprehensive information on tumor parameters was acquired from the Radiomics Signatures for Precision Oncology in Glioblastoma consortium. Data imputation was performed for missing values. Sex-based differences in tumor parameters, such as age, molecular parameters, preoperative Karnofsky performance score (KPS), tumor volumes, epicenter, and laterality were assessed through nonparametric tests. Spatial atlases were generated by using preoperative MRI maps to visualize tumor characteristics. Survival time analysis was performed through log-rank tests and Cox proportional hazard analyses. RESULTS: Glioblastoma was diagnosed at a median age of 64 years in women compared with 61.9 years in men (false discovery rate [FDR] = 0.003). Men had a higher KPS (above 80) as compared with women (60.4% women versus 69.7% men, FDR = 0.044). Women had lower tumor volumes in enhancing (16.7 cm3 versus 20.6 cm3 in men, FDR = 0.001), necrotic core (6.18 cm3 versus 7.76 cm3 in men, FDR = 0.001), and edema regions (46.9 cm3 versus 59.2 cm3 in men, FDR = 0.0001). The right temporal region was the most common tumor epicenter in the overall population. Right as well as left temporal lobes were more frequently involved in men. There were no sex-specific differences in survival outcomes and mortality ratios. Higher age, unmethylated O6-methylguanine-DNA-methyltransferase promoter and undergoing subtotal resection increased the mortality risk in both men and women. CONCLUSIONS: Our study demonstrates significant sex-based differences in clinical and radiologic tumor parameters of patients with glioblastoma. Sex is not an independent prognostic factor for survival outcomes and the tumor parameters influencing patient outcomes are identical for men and women.


Assuntos
Neoplasias Encefálicas , Isocitrato Desidrogenase , Humanos , Masculino , Feminino , Isocitrato Desidrogenase/genética , Pessoa de Meia-Idade , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Estudos Retrospectivos , Idoso , Fatores Sexuais , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioblastoma/mortalidade , Glioblastoma/patologia , Imageamento por Ressonância Magnética , Adulto , Gradação de Tumores , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/patologia , Glioma/mortalidade , Taxa de Sobrevida
14.
ArXiv ; 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37426455

RESUMO

BACKGROUND: A noninvasive and sensitive imaging tool is needed to assess the fast-evolving baby brain. However, using MRI to study non-sedated babies faces roadblocks, including high scan failure rates due to subjects motion and the lack of quantitative measures for assessing potential developmental delays. This feasibility study explores whether MR Fingerprinting scans can provide motion-robust and quantitative brain tissue measurements for non-sedated infants with prenatal opioid exposure, presenting a viable alternative to clinical MR scans. ASSESSMENT: MRF image quality was compared to pediatric MRI scans using a fully crossed, multiple reader multiple case study. The quantitative T1 and T2 values were used to assess brain tissue changes between babies younger than one month and babies between one and two months. STATISTICAL TESTS: Generalized estimating equations (GEE) model was performed to test the significant difference of the T1 and T2 values from eight white matter regions of babies under one month and those are older. MRI and MRF image quality were assessed using Gwets second order auto-correlation coefficient (AC2) with its confidence levels. We used the Cochran-Mantel-Haenszel test to assess the difference in proportions between MRF and MRI for all features and stratified by the type of features. RESULTS: In infants under one month of age, the T1 and T2 values are significantly higher (p<0.005) compared to those between one and two months. A multiple-reader and multiple-case study showed superior image quality ratings in anatomical features from the MRF images than the MRI images. CONCLUSIONS: This study suggested that the MR Fingerprinting scans offer a motion-robust and efficient method for non-sedated infants, delivering superior image quality than clinical MRI scans and additionally providing quantitative measures to assess brain development.

15.
J Pers Soc Psychol ; 122(4): 731-748, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35254856

RESUMO

What do people think their best and worst personality traits are? Do their friends agree? Across three samples, 463 college students ("targets") and their friends freely described two traits they most liked and two traits they most disliked about the target. Coders categorized these open-ended trait descriptors into high or low poles of six trait domains (extraversion, agreeableness, conscientiousness, emotional stability, openness, and honesty-humility) and judged whether targets and friends reported the same specific best and worst traits. Best traits almost exclusively reflected high levels of the major trait domains (especially high agreeableness and extraversion). In contrast, although worst traits typically reflected low levels of these traits (especially low emotional stability), they sometimes also revealed the downsides of having high levels of these traits (e.g., high extraversion: "loud"; high agreeableness: "people-pleaser"). Overall, targets and friends mentioned similar kinds of best traits; however, targets emphasized low emotional stability worst traits more than friends did, whereas friends emphasized low prosociality worst traits more than targets did. Targets and friends also showed a moderate amount of self-other agreement on what the targets' best and worst traits were. These results (a) shed light on the traits that people consider to be most important in themselves and their friends, (b) suggest that the desirability of some traits may be in the eye of the beholder, (c) reveal the mixed blessings of different traits, and, ultimately, (d) provide a nuanced perspective on what it means for a trait to be "good" or "bad." (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Extroversão Psicológica , Amigos , Emoções , Amigos/psicologia , Humanos , Personalidade , Transtornos da Personalidade
16.
Clin Transl Sci ; 15(11): 2720-2731, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36045613

RESUMO

The cytochrome P450 3As (CYP3As) are abundantly expressed in the liver and metabolize many commonly prescribed medications. Their expression is highly variable between individuals with little known genetic cause. Despite extensive investigation, cis-acting genetic elements that control the expression of the CYP3As remain uncharacterized. Using chromatin conformation capture (4C assays), we detected reciprocal interaction between a distal regulatory region (DRR) and the CYP3A4 promoter. The DRR colocalizes with a variety of enhancer marks and was found to promote transcription in reporter assays. CRISPR-mediated deletion of the DRR decreased expression of CYP3A4, CYP3A5, and CYP3A7, supporting its role as a shared enhancer regulating the expression of three CYP3A genes. Using reporter gene assays, we identified two single-nucleotide polymorphisms (rs115025140 and rs776744/rs776742) that increased DRR-driven luciferase reporter expression. In a liver cohort (n = 246), rs115025140 was associated with increased expression of CYP3A4 mRNA (1.8-fold) and protein (1.6-fold) and rs776744/rs776742 was associated with 1.39-fold increased expression of CYP3A5 mRNA. The rs115025140 is unique to the African population and in a clinical cohort of African Americans taking statins for lipid control rs115025140 carriers showed a trend toward reduced statin-mediated lipid reduction. In addition, using a published cohort of Chinese patients who underwent renal transplantation taking tacrolimus, rs776744/rs776742 carriers were associated with reduced tacrolimus concentration after adjusting for CYP3A5*3. Our results elucidate a complex regulatory network controlling expression of three CYP3A genes and identify two novel regulatory variants with potential clinical relevance for predicting CYP3A4 and CYP3A5 expression.


Assuntos
Citocromo P-450 CYP3A , Tacrolimo , Humanos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Tacrolimo/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Sequências Reguladoras de Ácido Nucleico , RNA Mensageiro/genética , Lipídeos
17.
Pers Soc Psychol Bull ; 47(11): 1535-1549, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33342369

RESUMO

Participants in experience sampling method (ESM) studies are "beeped" several times per day to report on their momentary experiences-but participants do not always answer the beep. Knowing whether there are systematic predictors of missing a report is critical for understanding the extent to which missing data threatens the validity of inferences from ESM studies. Here, 228 university students completed up to four ESM reports per day while wearing the Electronically Activated Recorder (EAR)-an unobtrusive audio recording device-for a week. These audio recordings provided an alternative source of information about what participants were doing when they missed or completed reports (3,678 observations). We predicted missing ESM reports from 46 variables coded from the EAR recordings, and found very little evidence that missing an ESM report was correlated with constructs typically of interest to ESM researchers. These findings provide reassuring evidence for the validity of ESM research among relatively healthy university student samples.


Assuntos
Avaliação Momentânea Ecológica , Universidades , Humanos , Estudantes
18.
J Control Release ; 329: 1162-1171, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33127451

RESUMO

Nanoparticles must recognize, adhere to, and/or traverse multiple barriers in sequence to achieve cytosolic drug delivery. New nanoparticles often exhibit a unique ability to cross a single barrier (i.e. the vasculature, cell membrane, or endosomal compartment), but fail to deliver an adequate dose to intracellular sites of action because they cannot traverse other biological barriers for which they were not optimized. Here, we developed poly(acrylamide-co-methacrylic acid) nanogels that were modified in a modular manner with bioactive peptides. This nanogel does not recognize target cells or disrupt endosomal vesicles in its unmodified state, but can incorporate peptides with molecular recognition or environmentally responsive properties. Nanogels were modified with up to 15 wt% peptide without significantly altering their size, surface charge, or stability in aqueous buffer. Nanogels modified with a colon cancer-targeting oligopeptide exhibited up to a 324% enhancement in co-localization with SW-48 colon cancer cells in vitro, while influencing nanogel uptake by fibroblasts and macrophages to a lesser extent. Nanogels modified with an endosome disrupting peptide failed to retain its native endosomolytic activity, when coupled either individually or in combination with the targeting peptide. Our results offer a proof-of-concept for modifying synthetic nanogels with a combination of peptides that address barriers to cytosolic delivery individually and in tandem. Our data further motivate the need to identify endosome disrupting moieties which retain their activity within poly(acidic) networks.


Assuntos
Nanopartículas , Acrilamidas , Endossomos , Metacrilatos , Nanogéis , Peptídeos
19.
Artigo em Inglês | MEDLINE | ID: mdl-35434719

RESUMO

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.

20.
J Pers Soc Psychol ; 119(6): 1478-1496, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31647273

RESUMO

Social relationships are often touted as critical for well-being. However, the vast majority of studies on social relationships have relied on self-report measures of both social interactions and well-being, which makes it difficult to disentangle true associations from shared method variance. To address this gap, we assessed the quantity and quality of social interactions using both self-report and observer-based measures in everyday life. Participants (N = 256; 3,206 observations) wore the Electronically Activated Recorder (EAR), an unobtrusive audio recorder, and completed experience sampling method self-reports of their momentary social interactions, happiness, and feelings of social connectedness, 4 times each day for 1 week. Observers rated the quantity and quality of participants' social interactions based on the EAR recordings from the same time points. Quantity of social interactions was robustly associated with greater well-being in the moment and on average, whether they were measured with self-reports or observer reports. Conversational (conversational depth and self-disclosure) and relational (knowing and liking one's interaction partners) aspects of social interaction quality were also generally associated with greater well-being, but the effects were larger and more consistent for self-reported (vs. observer-reported) quality variables, within-person (vs. between-person) associations, and for predicting social connectedness (vs. happiness). Finally, although most associations were similar for introverts and extraverts, our exploratory results suggest that introverts may experience greater boosts in social connectedness, relative to extraverts, when engaging in deeper conversations. This study provides compelling multimethod evidence supporting the link between more frequent and deeper social interactions and well-being. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Emoções , Satisfação Pessoal , Personalidade , Interação Social , Adulto , Avaliação Momentânea Ecológica , Feminino , Humanos , Masculino , Autorrelato
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