Sex-specific Differences in IDH1-Wildtype Glioblastoma patients in the ReSPOND Consortium.

BACKGROUND: Understanding sex-based differences in glioblastoma patients is necessary for accurate personalized treatment planning to improve patient outcomes. PURPOSE: To investigate sex-specific differences in molecular, clinical and radiological tumor parameters, as well as survival outcomes in glioblastoma, isocitrate dehydrogenase-1 wildtype (IDH1-WT), grade 4 patients. METHODS: Retrospective data of 1832 glioblastoma, IDH1-WT patients with comprehensive information on tumor parameters was acquired from the Radiomics Signatures for Precision Oncology in Glioblastoma (ReSPOND) consortium. Data imputation was performed for missing values. Sex-based differences in tumor parameters, such as, age, molecular parameters, pre-operative KPS score, tumor volumes, epicenter and laterality were assessed through non-parametric tests. Spatial atlases were generated using pre-operative MRI maps to visualize tumor characteristics. Survival time analysis was performed through log-rank tests and Cox proportional hazard analyses. RESULTS: GBM was diagnosed at a median age of 64 years in females compared to 61.9 years in males (FDR = 0.003). Males had a higher Karnofsky Performance Score (above 80) as compared to females (60.4% females Vs 69.7% males, FDR = 0.044). Females had lower tumor volumes in enhancing (16.7 cm3 Vs. 20.6 cm3 in males, FDR = 0.001), necrotic core (6.18 cm3 Vs. 7.76 cm3 in males, FDR = 0.001) and edema regions (46.9 cm3 Vs. 59.2 cm3 in males, FDR = 0.0001). 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 males. There were no significant differences in survival outcomes and mortality ratios. Higher age, unmethylated O6-methylguanine-DNAmethyltransferase (MGMT) promoter and undergoing subtotal resection increased the mortality risk in both males and females. CONCLUSIONS: Our study demonstrates significant sex-based differences in clinical and radiological tumor parameters of glioblastoma, IDH1-WT, grade 4 patients. Sex is not an independent prognostic factor for survival outcomes and the tumor parameters influencing patient outcomes are identical for males and females. ABBREVIATIONS: IDH1-WT = isocitrate dehydrogenase-1 wildtype; MGMTp = O6-methylguanine-DNA-methyltransferase promoter; KPS = Karnofsky performance score; EOR = extent of resection; WHO = world health organization; FDR = false discovery rate.

Hydrogenolysis of Poly(Ethylene-co-Vinyl Alcohol) and Related Polymer Blends over Ruthenium Heterogeneous Catalysts.

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.

Why moral psychology needs personality psychology.

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.

Quantifying 3D MR fingerprinting (3D-MRF) reproducibility across subjects, sessions, and scanners automatically using MNI atlases.

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.

Motion Robust MR Fingerprinting Scan to Image Neonates With Prenatal Opioid Exposure.

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.

Self-calibrated subspace reconstruction for multidimensional MR fingerprinting for simultaneous relaxation and diffusion quantification.

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.

What is the moral person like? An examination of the shared and unique perspectives on moral character.

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.

Motion robust MR fingerprinting scan to image neonates with prenatal opioid exposure.

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.

How and why people want to be more moral.

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.

Regulatory variants in a novel distal enhancer regulate the expression of CYP3A4 and CYP3A5.

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.

Personality evaluated: What do people most like and dislike about themselves and their friends?

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).

Why Has Personality Psychology Played an Outsized Role in the Credibility Revolution?

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.

Peptide conjugation enhances the cellular co-localization, but not endosomal escape, of modular poly(acrylamide-co-methacrylic acid) nanogels.

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.

Eavesdropping on Missing Data: What Are University Students Doing When They Miss Experience Sampling Reports?

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.

Do People Want to Be More Moral?

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.

The language of well-being: Tracking fluctuations in emotion experience through everyday speech.

The words that people use have been found to reflect stable psychological traits, but less is known about the extent to which everyday fluctuations in spoken language reflect transient psychological states. We explored within-person associations between spoken words and self-reported state emotion among 185 participants who wore the Electronically Activated Recorder (EAR; an unobtrusive audio recording device) and completed experience sampling reports of their positive and negative emotions 4 times per day for 7 days (1,579 observations). We examined language using the Linguistic Inquiry and Word Count program (LIWC; theoretically created dictionaries) and open-vocabulary themes (clusters of data-driven semantically-related words). Although some studies give the impression that LIWC's positive and negative emotion dictionaries can be used as indicators of emotion experience, we found that when computed on spoken language, LIWC emotion scores were not significantly associated with self-reports of state emotion experience. Exploration of other categories of language variables suggests a number of hypotheses about substantive everyday correlates of momentary positive and negative emotion that can be tested in future studies. These findings (a) suggest that LIWC positive and negative emotion dictionaries may not capture self-reported subjective emotion experience when applied to everyday speech, (b) emphasize the importance of establishing the validity of language-based measures within one's target domain, (c) demonstrate the potential for developing new hypotheses about personality processes from the open-ended words that are used in everyday speech, and (d) extend perspectives on intraindividual variability to the domain of spoken language. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

(Not) hearing happiness: Predicting fluctuations in happy mood from acoustic cues using machine learning.

Recent popular claims surrounding virtual assistants suggest that computers will soon be able to hear our emotions. Supporting this possibility, promising work has harnessed big data and emergent technologies to automatically predict stable levels of one specific emotion, happiness, at the community (e.g., counties) and trait (i.e., people) levels. Furthermore, research in affective science has shown that nonverbal vocal bursts (e.g., sighs, gasps) and specific acoustic features (e.g., pitch, energy) can differentiate between distinct emotions (e.g., anger, happiness) and that machine-learning algorithms can detect these differences. Yet, to our knowledge, no work has tested whether computers can automatically detect normal, everyday, within-person fluctuations in one emotional state from acoustic analysis. To address this issue in the context of happy mood, across 3 studies (total N = 20,197), we asked participants to repeatedly report their state happy mood and to provide audio recordings-including both direct speech and ambient sounds-from which we extracted acoustic features. Using three different machine learning algorithms (neural networks, random forests, and support vector machines) and two sets of acoustic features, we found that acoustic features yielded minimal predictive insight into happy mood above chance. Neither multilevel modeling analyses nor human coders provided additional insight into state happy mood. These findings suggest that it is not yet possible to automatically assess fluctuations in one emotional state (i.e., happy mood) from acoustic analysis, pointing to a critical future direction for affective scientists interested in acoustic analysis of emotion and automated emotion detection. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Is well-being associated with the quantity and quality of social interactions?

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).

A comparison of genetic sampling methodologies for candidate-gene analyses.

Much of the recent gains in knowledge regarding the influence of patient genetics on medication pharmacokinetics (drug absorption, distribution, metabolism and elimination) how patients process medications) and pharmacodynamics (drug response) have been attributed to the technologic advances in genetic testing methodologies and the involvement of large clinical data sets and biobanks. Indeed, Genome Wide Association Studies (GWAS) and Phenome Wide Association Studies (PWAS) along with ever-evolving biomedical informatics techniques and the expansion of the -omics sciences (e.g., transcriptomics, metabolomics, proteomics) have brought about unprecedented advances in precision medicine. Although the simpler candidate-gene analysis technique is not considered cutting-edge, it is reliable and important to the translation of pharmacogenomic research and the advancement of precision medicine. Leveraging the knowledge of biological plausibility (i.e., genetic mutation → altered function of protein product → altered drug pharmacokinetics/dynamics) to appropriately select genes for inclusion, the candidate-gene analysis technique does not necessitate large patient cohorts nor extensive multi-gene genetic analysis arrays. It is often the ideal method for clinicians to begin evaluating whether genetic information might improve their pharmacologic treatment strategies for their patients. Having access to specific patient populations and expertise regarding their medical subspecialty, physician scientists can implement a candidate-gene analysis in small cohorts. Even with less than 100 patients, results can often be used to determine whether further investigation is warranted and to inform future studies. Herein, we present a comparison of select contemporary methodologies regarding collection, processing and genotype testing applicable to the efficient implementation of candidate-gene studies.

Association of Genetic Polymorphisms in the Beta-1 Adrenergic Receptor with Recovery of Left Ventricular Ejection Fraction in Patients with Heart Failure.

Two common genetic polymorphisms in the beta-1 adrenergic receptor (ADRB1 Ser49Gly [rs1801252] and Arg389Gly [rs1801253]) significantly affect receptor function in vitro. The objective of this study was to determine whether ADRB1 Ser49Gly and Arg389Gly are associated with recovery of left ventricular ejection fraction (LVEF) in patients with heart failure. Patients with heart failure and baseline LVEF ≤ 40% were genotyped (n = 98), and retrospective chart review assessed the primary outcome of LVEF recovery to ≥ 40%. Un/adjusted logistic regression models revealed that Ser49Gly, but not Arg389Gly, was significantly associated with LVEF recovery in a dominant genetic model. The adjusted odds ratio for Ser49 was 8.2 (95% CI = 2.1-32.9; p = 0.003), and it was the strongest predictor of LVEF recovery among multiple clinical variables. In conclusion, patients with heart failure and reduced ejection fraction that are homozygous for ADRB1 Ser49 were significantly more likely to experience LVEF recovery than Gly49 carriers.