Diagnostic evaluation of deep learning accelerated lumbar spine MRI.

BACKGROUND AND PURPOSE: Deep learning (DL) accelerated MR techniques have emerged as a promising approach to accelerate routine MR exams. While prior studies explored DL acceleration for specific lumbar MRI sequences, a gap remains in comprehending the impact of a fully DL-based MRI protocol on scan time and diagnostic quality for routine lumbar spine MRI. To address this, we assessed the image quality and diagnostic performance of a DL-accelerated lumbar spine MRI protocol in comparison to a conventional protocol. METHODS: We prospectively evaluated 36 consecutive outpatients undergoing non-contrast enhanced lumbar spine MRIs. Both protocols included sagittal T1, T2, STIR, and axial T2-weighted images. Two blinded neuroradiologists independently reviewed images for foraminal stenosis, spinal canal stenosis, nerve root compression, and facet arthropathy. Grading comparison employed the Wilcoxon signed rank test. For the head-to-head comparison, a 5-point Likert scale to assess image quality, considering artifacts, signal-to-noise ratio (SNR), anatomical structure visualization, and overall diagnostic quality. We applied a 15% noninferiority margin to determine whether the DL-accelerated protocol was noninferior. RESULTS: No significant differences existed between protocols when evaluating foraminal and spinal canal stenosis, nerve compression, or facet arthropathy (all p > .05). The DL-spine protocol was noninferior for overall diagnostic quality and visualization of the cord, CSF, intervertebral disc, and nerve roots. However, it exhibited reduced SNR and increased artifact perception. Interobserver reproducibility ranged from moderate to substantial (κ = 0.50-0.76). CONCLUSION: Our study indicates that DL reconstruction in spine imaging effectively reduces acquisition times while maintaining comparable diagnostic quality to conventional MRI.

A KRAS-responsive long non-coding RNA controls microRNA processing.

Wild-type KRAS (KRASWT) amplification has been shown to be a secondary means of KRAS activation in cancer and associated with poor survival. Nevertheless, the precise role of KRASWT overexpression in lung cancer progression is largely unexplored. Here, we identify and characterize a KRAS-responsive lncRNA, KIMAT1 (ENSG00000228709) and show that it correlates with KRAS levels both in cell lines and in lung cancer specimens. Mechanistically, KIMAT1 is a MYC target and drives lung tumorigenesis by promoting the processing of oncogenic microRNAs (miRNAs) through DHX9 and NPM1 stabilization while halting the biogenesis of miRNAs with tumor suppressor function via MYC-dependent silencing of p21, a component of the Microprocessor Complex. KIMAT1 knockdown suppresses not only KRAS expression but also KRAS downstream signaling, thereby arresting lung cancer growth in vitro and in vivo. Taken together, this study uncovers a role for KIMAT1 in maintaining a positive feedback loop that sustains KRAS signaling during lung cancer progression and provides a proof of principle that interfering with KIMAT1 could be a strategy to hamper KRAS-induced tumorigenesis.

CKAP2L Promotes Non-Small Cell Lung Cancer Progression through Regulation of Transcription Elongation.

Chromosomal instability (CIN) is a driver of clonal diversification and intratumor heterogeneity, providing genetic diversity that contributes to tumor progression. It is estimated that approximately 80% of solid cancers, including non-small cell lung cancer (NSCLC), exhibit features of CIN, which affects tumor growth and response to therapy. However, the molecular mechanisms connecting CIN to tumor progression are still poorly understood. Through an RNAi screen performed on genes involved in CIN and overexpressed in human lung adenocarcinoma samples, we identified the cytoskeleton-associated protein 2-like (CKAP2L) as a potential oncogene that promotes lung cancer proliferation and growth in vitro and in vivo. Mechanistically, CKAP2L directly interacted with RNA Pol II and regulated transcription elongation of key genes involved in spindle assembly checkpoint, chromosome segregation, cell cycle, and E2F signaling. Furthermore, depletion of CKAP2L increased the sensitivity of NSCLC cells to alvocidib, a pan-CDK inhibitor, leading to a significant reduction of cell proliferation and an increase in cell death. Altogether, these findings shed light on the molecular mechanisms through which CKAP2L, a protein involved in CIN, promotes cancer progression and suggest that its inhibition represents a novel therapeutic strategy in NSCLC. SIGNIFICANCE: These findings demonstrate the oncogenic function of CKAP2L through regulation of transcription elongation and suggest that targeting CKAP2L could enhance therapeutic response in patients with NSCLC.

Ancestry of the AUTS2 family-A novel group of polycomb-complex proteins involved in human neurological disease.

Autism susceptibility candidate 2 (AUTS2) is a neurodevelopmental regulator associated with an autosomal dominant intellectual disability syndrome, AUTS2 syndrome, and is implicated as an important gene in human-specific evolution. AUTS2 exists as part of a tripartite gene family, the AUTS2 family, which includes two relatively undefined proteins, Fibrosin (FBRS) and Fibrosin-like protein 1 (FBRSL1). Evolutionary ancestors of AUTS2 have not been formally identified outside of the Animalia clade. A Drosophila melanogaster protein, Tay bridge, with a role in neurodevelopment, has been shown to display limited similarity to the C-terminal of AUTS2, suggesting that evolutionary ancestors of the AUTS2 family may exist within other Protostome lineages. Here we present an evolutionary analysis of the AUTS2 family, which highlights ancestral homologs of AUTS2 in multiple Protostome species, implicates AUTS2 as the closest human relative to the progenitor of the AUTS2 family, and demonstrates that Tay bridge is a divergent ortholog of the ancestral AUTS2 progenitor gene. We also define regions of high relative sequence identity, with potential functional significance, shared by the extended AUTS2 protein family. Using structural predictions coupled with sequence conservation and human variant data from 15,708 individuals, a putative domain structure for AUTS2 was produced that can be used to aid interpretation of the consequences of nucleotide variation on protein structure and function in human disease. To assess the role of AUTS2 in human-specific evolution, we recalculated allele frequencies at previously identified human derived sites using large population genome data, and show a high prevalence of ancestral alleles, suggesting that AUTS2 may not be a rapidly evolving gene, as previously thought.

A Daily Examination of African American Adolescents' Racial Discrimination, Parental Racial Socialization, and Psychological Affect.

This study examined 164 African American adolescents' (Mage  = 15) daily reports of racial discrimination and parental racial socialization over 21 days. The study examined same-day and previous-day associations of adolescents' discrimination and socialization experiences with their positive and negative psychological affect. It further explored whether racial socialization messages buffered discrimination's effects on affect when messages were received during the same day and on the day prior to discrimination. Findings indicated the deleterious effect of racial discrimination (associated with more negative affect) and highlighted the importance of examining youth's short-term coping in critical developmental years. Findings also showed how messages promote positive youth emotions. However, daily moderating associations differed from prior survey studies, suggesting the importance of examining short-term processes.

Correction: A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome.

PURPOSE: To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1). METHODS: Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode a highly conserved region of 54 amino acids flanked by Val3527 and Lys3583, were identified and phenotyped. Functional tests were performed to study their pathogenicity and understand the disease mechanism. RESULTS: The consistent clinical features of the affected individuals, from seven unrelated families, included choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability. The frequency of clinical features, objective software-based facial analysis metrics, and genome-wide peripheral blood DNA methylation patterns in these patients were significantly different from that of KS1. Circular dichroism spectroscopy indicated that these MVs perturb KMT2D secondary structure through an increased disordered to ɑ-helical transition. CONCLUSION: KMT2D MVs located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from KS1. Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism.

Academic Identity: A Longitudinal Investigation of African American Adolescents' cademic Persistence.

Adolescence is a vulnerable period for the development of academic identification and academic persistence, particularly among African American adolescents. The present study investigated how cultural assets (i.e., private regard and racial centrality) and academic assets (i.e., academic curiosity and academic self-esteem) influence African American adolescent boys' (n = 109) and girls' (n = 153) academic persistence over time. Additionally, we explored whether oppositional academic identity mediated the relationships between academic and cultural assets and academic persistence. Data were drawn from a cross-sectional longitudinal study. Results indicated significant direct effects of academic assets on academic persistence at Times 1 and 2 for boys and at Times 1, 2, and 3 for girls. Furthermore, oppositional academic identity mediated the relationship between boys', but not girls', cultural assets and academic persistence at Time 1. These findings have implications for understanding the role of assets in the lives of African American youth.

The Role of Racial Identity and Implicit Racial Bias in Self-Reported Racial Discrimination: Implications for Depression Among African American Men.

Racial discrimination is conceptualized as a psychosocial stressor that has negative implications for mental health. However, factors related to racial identity may influence whether negative experiences are interpreted as instances of racial discrimination and subsequently reported as such in survey instruments, particularly given the ambiguous nature of contemporary racism. Along these lines, dimensions of racial identity may moderate associations between racial discrimination and mental health outcomes. This study examined relationships between racial discrimination, racial identity, implicit racial bias, and depressive symptoms among African American men between 30 and 50 years of age (n = 95). Higher racial centrality was associated with greater reports of racial discrimination, while greater implicit anti-Black bias was associated with lower reports of racial discrimination. In models predicting elevated depressive symptoms, holding greater implicit anti-Black bias in tandem with reporting lower racial discrimination was associated with the highest risk. Results suggest that unconscious as well as conscious processes related to racial identity are important to consider in measuring racial discrimination, and should be integrated in studies of racial discrimination and mental health.

Capturing the cardiac effects of racial discrimination: Do the effects "keep going"?

Racial discrimination negatively impacts cardiac functioning, but few studies examine the more distal cardiac effects of racial discrimination experiences. The present study examined the momentary and prolonged impact of lab-based intergroup and intragroup racial discrimination on heart rate variability (HRV) and heart rate (HR) in a sample (N = 42) of African American (AA) women across two days. On day one, the women were exposed to simulated racial discrimination from either a European American (EA) or AA confederate in the lab. On day two, the women returned to the lab for additional physiological recording and debriefing. Women insulted by the EA confederate exhibited lower HRV on day one and marginally lower HRV on day two. These women also exhibited marginally higher HR on day two. The HRV and HR effects on day two were not mediated by differences in perseveration about the stressor. The findings indicate that racial discrimination - particularly intergroup racial discrimination - may have both momentary and prolonged effects on cardiac activity in AAs.

The lagged effects of racial discrimination on depressive symptomology and interactions with racial identity.

Scholars agree on the negative impacts of racial discrimination on the mental health of African Americans (Brondolo et al., 2008). Yet research is needed to explore the impacts of everyday discrimination over time, especially compared to nonracial daily hassles, in an ecologically valid manner. It is also widely accepted that racial identity can moderate the impact of racial hassles (Sellers, Copeland-Linder, Martin, & Lewis 2006), but few studies have examined this moderating effect over time. The current study addresses gaps in the current literature by analyzing the relationship between reported racial and nonracial stressors over the course of four days. Participants were 225 college students at three institutions who participated in a 20-day daily diary study. Each day, participants reported whether they had experienced a stressful event and their depressive symptoms. We compared reports of depressive symptoms the day an event occurred and two days after for racial and nonracial stressors and examined whether racial identity served as a moderator. The results showed that individuals experienced similar increases for racial and nonracial stressors when events occur and similar decreases in the following two days. Additionally, symptom trajectories varied by racial identity. Implications for the understanding of racial discrimination's role in the well-being of African Americans are discussed.

Black adolescents' relationships with natural mentors: associations with academic engagement via social and emotional development.

This study aimed to identify types of natural mentoring relationships that Black adolescents may experience and to connect these relationship types to academic outcomes via social and emotional development. Data were collected from 259 adolescents attending 3 middle schools in a Midwestern metropolitan area. Adolescents reported on whether or not they had a relationship with a natural mentor and answered several questions about characteristics of the relationship, as well as reporting on a number of indicators of positive development. Cluster analyses suggested two different types of natural mentoring relationships among study youth: less connected and more connected. We found that in comparison with youth without a natural mentor, youth who had a more connected natural mentoring relationship had greater student-reported academic engagement via higher social skills and psychological well-being and greater teacher-reported academic engagement via elevated social skills. We found that youth with less connected natural mentoring relationships did not differ from their counterparts without natural mentors on social skills, psychological well-being, or student- or teacher-reported academic engagement. Findings from the current study suggest that characteristics of the mentoring relationship may determine whether these relationships contribute to more positive outcomes among Black youth. Further, findings suggest that social and emotional development may transmit the positive effects of more connected natural mentoring relationships on Black youths' academic engagement.

Racial identity and depressive symptoms among Black emerging adults: the moderating effects of neighborhood racial composition.

In the current study, we explored patterns of change in Black emerging adults' racial identity beliefs during the transition to adulthood, assessed neighborhood racial composition effects on Black emerging adults' racial identity beliefs, and tested the moderating effects of neighborhood racial composition on the associations between Black emerging adults' racial identity beliefs and depressive symptoms over time. Participants in the current study included 570 Black adolescents (52% female) who were transitioning into adulthood (senior year of high school through 5 years post- high school). We did not find average patterns of change in Black emerging adults' racial identity beliefs over time. Further, neighborhood racial composition did not predict participants' beginning status or growth in racial identity beliefs over time. We, however, found evidence that neighborhood racial composition may moderate the associations between Black emerging adults' racial identity beliefs and symptoms of depression over time. Findings from the current study underscore the importance of considering how the larger social context may interact with individuals' racial identity beliefs to influence Black emerging adults' psychological health.

Caregiver experiences of discrimination and african american adolescents' psychological health over time.

The present study examined the effect of caregivers' experiences of racial discrimination on their adolescent children's psychological functioning among a sample of 264 African American dyads. Potential relations between caregiver discrimination experiences and a number of indicators of adolescents' (aged 12-17) psychological functioning over time were examined. It was found that caregiver discrimination experiences were positively related to adolescents' symptoms of depression and negatively related to their psychological well-being. Additional analysis revealed interactions between the effects of caregiver discrimination experiences and family income on all 3 outcomes. Greater caregiver discrimination experiences and lower family income were risk factors for the youth in the sample. These findings underscore the deleterious consequence of caregivers' discrimination experiences on African American youth's psychological health.

Progress towards the synthesis of Urukthapelstatin A and two analogues.

We report our progress towards the synthesis of Urukthapelstatin A (Ustat A) and two analogues. Our retrosynthetic strategy involved the synthesis of three fragments: a tri-heteroaromatic moiety, a phenyl oxazole fragment, and a dipeptide. Described are the syntheses of three unique tri-heteroaromatic moieties. In addition, the corresponding linear precursors of Ustat A and two analogues are presented.

Comparison of African American college students' coping with racially and nonracially stressful events.

Racial discrimination, a common experience for many African Americans, has been conceptualized within a stress and coping framework. However, few have examined whether racially stressful events are appraised and coped with differently from nonracially stressful events. The present study uses a daily diary method to examine African American college students' appraisals and coping behaviors in racially and nonracially stressful situations. The study examines the following 3 questions: 1) Do African Americans appraise racially stressful events differently from nonracially stressful events? 2) Do they cope with racially stressful events differently from nonracially stressful events? and 3) Do they cope with racially stressful events differently from nonracially stressful events, even after controlling for differences in cognitive appraisals of the events? The present sample consists of 35 participants who reported experiencing at least one racially stressful event and at least one nonracially stressful event during a 20-day diary study. Overall, no differences were found in students' appraisals in the racially stressful versus nonracially stressful events. Participants used less planful problem solving and more confrontive, ruminative, and avoidance coping strategies in the racially stressful events as compared with the nonracially stressful events. These findings suggest a need for race-specific models for coping with racial discrimination. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Racial discrimination and racial socialization as predictors of African American adolescents' racial identity development using latent transition analysis.

The present study examined perceptions of racial discrimination and racial socialization on racial identity development among 566 African American adolescents over 3 years. Latent class analyses were used to estimate identity statuses (Diffuse, Foreclosed, Moratorium, and Achieved). The probabilities of transitioning from one stage to another were examined with latent transition analyses to determine the likelihood of youth progressing, regressing, or remaining constant. Racial socialization and perceptions of racial discrimination were examined as covariates to assess the association with changes in racial identity status. The results indicated that perceptions of racial discrimination were not linked to any changes in racial identity. Youth who reported higher levels of racial socialization were less likely to be in Diffuse or Foreclosed compared with the Achieved group.

The moderating capacity of racial identity between perceived discrimination and psychological well-being over time among African American youth.

This study examined the influence of racial identity in the longitudinal relation between perceptions of racial discrimination and psychological well-being for approximately 560 African American youth. Latent curve modeling (LCM) and parallel process multiple-indicator LCMs with latent moderators were used to assess whether perceptions of racial discrimination predicted the intercept (initial levels) and the slope (rate of change) of psychological well-being over time, and whether racial identity moderates these relations. The results indicated that African American adolescents who reported higher psychological responses to discrimination frequency levels at the first time point had lower initial levels of well-being. Regressing the slope factor for psychological well-being on the frequency of discrimination also revealed a nonsignificant result for subsequent well-being levels.

Interracial and intraracial contact, school-level diversity, and change in racial identity status among African American adolescents.

Among 224 African American adolescents (mean age=14), the associations between interracial and intraracial contact and school-level diversity on changes in racial identity over a 3-year period were examined. Youths were determined to be diffused, foreclosed, moratorium, or achieved, and change or stability in identity status was examined. Contact with Black students, Black friends, and White friends predicted change in identity status. Furthermore, in racially diverse schools, having more Black friends was associated with identity stability. Students reporting low contact with Black students in racially diverse schools were more likely to report identity change if they had few Black friends. In students reporting high contact with Blacks in predominantly White schools, their identity was less likely to change for students with fewer White friends.

An intersectional approach for understanding perceived discrimination and psychological well-being among African American and Caribbean Black youth.

The present study examined whether combinations of ethnicity, gender, and age moderated the association between perceived discrimination and psychological well-being indicators (depressive symptoms, self-esteem, and life satisfaction) in a nationally representative sample of Black youth. The data were from the National Survey of American Life, which includes 810 African American and 360 Caribbean Black adolescents. The results indicated main effects such that perceived discrimination was linked to increased depressive symptoms and decreased self-esteem and life satisfaction. Additionally, there were significant interactions for ethnicity, gender, and race. Specifically, older Caribbean Black female adolescents exhibited higher depressive symptoms and lower life satisfaction in the context of high levels of perceived discrimination compared with older African American male adolescents.