Technical and biological sources of noise confound multiplexed enhancer AAV screening.

-acting regulatory enhancer elements are valuable tools for gaining cell type-specific genetic access. Leveraging large chromatin accessibility atlases, putative enhancer sequences can be identified and deployed in adeno-associated virus (AAV) delivery platforms. However, a significant bottleneck in enhancer AAV discovery is charting their detailed expression patterns , a process that currently requires gold-standard one-by-one testing.

COVID-19 Prevention Practices and Vaccine Acceptability Among Hispanic and Non-Hispanic Households in an Agricultural Community-Washington, 2020.

Objective: To investigate COVID-19 disparities between Hispanic/Latino persons (H/L) and non-H/L persons in an agricultural community by examining behavioral and demographic differences.

Methods: In September 2020, we conducted Community Assessments for Public Health Emergency Response in Wenatchee and East Wenatchee, Washington, to evaluate differences between H/L and non-H/L populations in COVID-19 risk beliefs, prevention practices, household needs, and vaccine acceptability. We produced weighted sample frequencies.

Distinctive physiology of molecularly identified medium spiny neurons in the macaque putamen.

The distinctive physiology of striatal medium spiny neurons (MSNs) underlies their ability to integrate sensory and motor input. In rodents, MSNs have a hyperpolarized resting potential and low input resistance. When activated, they have a delayed onset of spiking and regular spike rate.

Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits.

We present an enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Best-in-class vectors were curated for accessing major striatal neuron populations including medium spiny neurons (MSNs), direct and indirect pathway MSNs, as well as Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes of virus delivery, and with diverse transgene cargos.

Areal specializations in the morpho-electric and transcriptomic properties of primate layer 5 extratelencephalic projection neurons.

Large-scale analysis of single-cell gene expression has revealed transcriptomically defined cell subclasses present throughout the primate neocortex with gene expression profiles that differ depending upon neocortical region. Here, we test whether the interareal differences in gene expression translate to regional specializations in the physiology and morphology of infragranular glutamatergic neurons by performing Patch-seq experiments in brain slices from the temporal cortex (TCx) and motor cortex (MCx) of the macaque. We confirm that transcriptomically defined extratelencephalically projecting neurons of layer 5 (L5 ET neurons) include retrogradely labeled corticospinal neurons in the MCx and find multiple physiological properties and ion channel genes that distinguish L5 ET from non-ET neurons in both areas.

Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species.

Proper brain function requires the assembly and function of diverse populations of neurons and glia. Single cell gene expression studies have mostly focused on characterization of neuronal cell diversity; however, recent studies have revealed substantial diversity of glial cells, particularly astrocytes. To better understand glial cell types and their roles in neurobiology, we built a new suite of adeno-associated viral (AAV)-based genetic tools to enable genetic access to astrocytes and oligodendrocytes.

Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain.

Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates.

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species.

Intravenous functional gene transfer throughout the brain of non-human primates using AAV.

Adeno-associated viruses (AAVs) promise robust gene delivery to the brain through non-invasive, intravenous delivery. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates (NHPs). Here we describe AAV.

Minnesota Multiphasic Personality Inventory-Adolescent-Restructured Form (MMPI-A-RF) characteristics of ADHD in a Korean psychiatric sample.

Global rates of attention-deficit/hyperactivity disorder (ADHD) have risen. In Korea, ADHD is associated with functional impairments and comorbidity with other psychological disorders. This study examined the correlates of ADHD in a psychiatric sample of Korean adolescents on the Minnesota Multiphasic Personality Inventory-Adolescent-Restructured Form (MMPI-A-RF).

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex.

Viral genetic tools that target specific brain cell types could transform basic neuroscience and targeted gene therapy. Here, we use comparative open chromatin analysis to identify thousands of human-neocortical-subclass-specific putative enhancers from across the genome to control gene expression in adeno-associated virus (AAV) vectors. The cellular specificity of reporter expression from enhancer-AAVs is established by molecular profiling after systemic AAV delivery in mouse.

Assessment of prescription stimulant misuse among college students using the MMPI-2-RF.

Prescription stimulant misuse (PSM) is a growing concern on college campuses and more research is needed to validate clinical measures commonly used for the assessment of risk for PSM among college students. The present study examined correlations between scores on the Minnesota Multiphasic Personality Inventory-Second Edition-Restructured Form (MMPI-2-RF) and self- and peer-reported misuse of prescription stimulants and other drugs in a sample of 96 pairs (included within a total N = 212) of undergraduate students. Nearly half of the participants (48%) reported that they had been offered prescription stimulants and one quarter (26%) reported trying someone else's prescription stimulant medications, often to perform better academically.

Evaluating the Measurement Invariance of MMPI-2-RF Restructured Clinical Scale 4 (Antisocial Behavior) between American and Korean Clinical Samples: Exploring Cultural and Translation Issues Affecting Item Responding.

Establishing the cross-cultural measurement invariance of psychometric scales is considered an essential step before scale means are compared across cultures. Although the MMPI instruments have been extensively researched, few studies have examined the measurement equivalence of MMPI scales in cross-cultural research. This study examined the measurement invariance of MMPI-2-RF Restructured Clinical Scale 4 (RC4; Antisocial Behavior) using multi-group confirmatory factor analysis with American and Korean clinical samples by (a) comparing a rationally-derived four-factor model (School Problems, Substance Abuse, Family Problems, and Violation of Social Norms) with a one-factor model, and (b) examining the measurement invariance of the RC4 four-factor model.

Bi-allelic Loss-of-Function Variants in NUP188 Cause a Recognizable Syndrome Characterized by Neurologic, Ocular, and Cardiac Abnormalities.

Nucleoporins (NUPs) are an essential component of the nuclear-pore complex, which regulates nucleocytoplasmic transport of macromolecules. Pathogenic variants in NUP genes have been linked to several inherited human diseases, including a number with progressive neurological degeneration. We present six affected individuals with bi-allelic truncating variants in NUP188 and strikingly similar phenotypes and clinical courses, representing a recognizable genetic syndrome; the individuals are from four unrelated families.

Methodological and statistical advances in the consideration of cultural diversity in assessment: A critical review of group classification and measurement invariance testing.

One of the most important considerations in psychological and educational assessment is the extent to which a test is free of bias and fair for groups with diverse backgrounds. Establishing measurement invariance (MI) of a test or items is a prerequisite for meaningful comparisons across groups as it ensures that test items do not function differently across groups. Demonstration of MI is particularly important in assessment settings where test scores are used in decision making.

Identification of genetic markers for cortical areas using a Random Forest classification routine and the Allen Mouse Brain Atlas.

The mammalian neocortex is subdivided into a series of cortical areas that are functionally and anatomically distinct and are often distinguished in brain sections using histochemical stains and other markers of protein expression. We searched the Allen Mouse Brain Atlas, a database of gene expression, for novel markers of cortical areas. To screen for genes that change expression at area borders, we employed a random forest algorithm and binary region classification.

A comparative evaluation of Korean MMPI-A and MMPI-A-RF Substance Abuse Scales.

Objective: The purpose of the present study was to compare psychometric properties of the Substance Abuse (SUB) Scale on the Korean Minnesota Multiphasic Personality Inventory-Adolescent-Restructured Form (MMPI-A-RF) with those on the Korean MMPI-A (the Alcohol/Drug Problem Acknowledgment Scale [ACK]), the Alcohol/Drug Problem Proneness Scale [PRO], and the MacAndrew Alcoholism Scale-Revised Scale [MAC-R]).

Method: Participants consisted of 237 Korean adolescent psychiatric patients whose scores on these measures were compared in terms of internal consistency and predictive validity.

Results: Scores on SUB exhibited superior internal consistency to that of the MMPI-A substance abuse scales.

The role of common method variance in MMPI-2-RF response option augmentation.

Several studies have shown that response option augmentation (ROA), or increasing the number of response options of the Minnesota Multiphasic Personality Inventory (MMPI)-2-RF, improves the reliability of scale scores but does not improve convergent validity. However, these studies have not taken into account the response format of criterion measures, which may represent a form of common method variance (CMV). This study examined ROA with the MMPI-2-RF to determine whether number of response options is a source of CMV that may have affected previous estimates of convergent validity.

A Comparison of the Descriptive Information from the MMPI-2 and MMPI-2-RF.

Do MMPI-2 or MMPI-2-RF profiles differ in how accurately they depict examinees? To explore this question, we examined differences in clinical descriptions of equivalent profiles from the two instruments. Fourteen valid MMPI-2 protocols from an archival private practice sample were scored as both the MMPI-2 and the MMPI-2-RF. The resulting 28 profiles were coded separately by four raters using the Midwestern Q-Sort.

Interpretive Reliability of Six Computer-Based Test Interpretation Programs for the Minnesota Multiphasic Personality Inventory-2.

The reliability of six Minnesota Multiphasic Personality Inventory-Second edition (MMPI-2) computer-based test interpretation (CBTI) programs was evaluated across a set of 20 commonly appearing MMPI-2 profile codetypes in clinical settings. Evaluation of CBTI reliability comprised examination of (a) interrater reliability, the degree to which raters arrive at similar inferences based on the same CBTI profile and (b) interprogram reliability, the level of agreement across different CBTI systems. Profile inferences drawn by four raters were operationalized using q-sort methodology.

Diagnostic reliability of MMPI-2 computer-based test interpretations.

Reflecting the common use of the MMPI-2 to provide diagnostic considerations, computer-based test interpretations (CBTIs) also typically offer diagnostic suggestions. However, these diagnostic suggestions can sometimes be shown to vary widely across different CBTI programs even for identical MMPI-2 profiles. The present study evaluated the diagnostic reliability of 6 commercially available CBTIs using a 20-item Q-sort task developed for this study.

Gender differences on the MMPI across American and Korean adult and adolescent normative samples.

The purpose of this study was to examine whether gender differences on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) and Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A; Butcher et al., 1992) items are comparable across 2 distinctive cultural samples: Americans and Koreans. Using large, representative adult and adolescent samples from both cultures, we found that the American samples were associated with a higher proportion of items with gender differences than the Korean samples.