Publications by authors named "Amy Y Zhao"

6 Publications

  • Page 1 of 1

The association between neighborhood quality, youth physical fitness, and modifiable cardiovascular disease risk factors.

Ann Epidemiol 2021 05 14;57:30-39. Epub 2021 Feb 14.

Department of Population Health Sciences, Duke University School of Medicine, Durham, NC; Department of Family Medicine & Community Health, Duke University School of Medicine, Durham, NC. Electronic address:

Purpose: Striking disparities persist in cardiovascular disease risk factors among minority youth. We examined the association between multiple indicators of neighborhood quality and minority youth fitness.

Methods: The primary exposure was the Child Opportunity Index (COI), a measure comprised of indicators that facilitate healthy child development. Outcome data were drawn from the 2018-2019 Fit2Play Study (Miami-Dade County, FL). Hotspot analysis evaluated COI spatial clustering. Generalized linear mixed models examined cross-sectional COI-fitness associations.

Results: The sample included 725 youth (53% Black, 43% Hispanic; 5-17 years). Significant neighborhood quality spatial clusters were identified (Gi* = -4.85 to 5.36). Adjusting for sociodemographics, walkability was associated with lower percentiles in body mass index (BMI) and diastolic blood pressure percentiles (DBP) (β = -5.25, 95% CI: -8.88, -1.62 and β = -3.95, 95% CI: -7.02, -0.89, respectively) for all, lower skinfold thickness (β = -4.83, 95% CI: -9.97, 0.31 and higher sit-ups (β = 1.67, 95% CI: -0.17, 3.50) among girls, and lower systolic blood pressure percentiles (SBP) (β = -4.75, 95% CI: -8.99, -0.52) among boys. Greenspace was associated with higher BMI (β = 6.17, 95% CI: 2.47, 9.87), SBP (β = 3.47, 95% CI: -0.05, 6.99), and DBP (β = 4.11, 95% CI: 1.08, 7.13).

Conclusions: COI indicators were positively associated with youth fitness. Disparities in youth cardiovascular disease risk may be modifiable through community interventions and built environment initiatives targeting select neighborhood factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.annepidem.2021.02.004DOI Listing
May 2021

Clinical and genomic factors associated with seizures in meningiomas.

J Neurosurg 2020 Dec 4:1-10. Epub 2020 Dec 4.

Departments of1Neurosurgery.

Objective: The association of seizures with meningiomas is poorly understood. Moreover, any relationship between seizures and the underlying meningioma genomic subgroup has not been studied. Herein, the authors report on their experience with identifying clinical and genomic factors associated with preoperative and postoperative seizure presentation in meningioma patients.

Methods: Clinical and genomic sequencing data on 394 patients surgically treated for meningioma at Yale New Haven Hospital were reviewed. Correlations between clinical, histological, or genomic variables and the occurrence of preoperative and postoperative seizures were analyzed. Logistic regression models were developed for assessing multiple risk factors for pre- and postoperative seizures. Mediation analyses were also conducted to investigate the causal pathways between genomic subgroups and seizures.

Results: Seventeen percent of the cohort had presented with preoperative seizures. In a univariate analysis, patients with preoperative seizures were more likely to have tumors with a somatic NF2 mutation (p = 0.020), WHO grade II or III tumor (p = 0.029), atypical histology (p = 0.004), edema (p < 0.001), brain invasion (p = 0.009), and worse progression-free survival (HR 2.68, 95% CI 1.30-5.50). In a multivariate analysis, edema (OR 3.11, 95% CI 1.46-6.65, p = 0.003) and atypical histology (OR 2.00, 95% CI 1.03-3.90, p = 0.041) were positive predictors of preoperative seizures, while genomic subgroup was not, such that the effect of an NF2 mutation was indirectly mediated through atypical histology and edema (p = 0.012). Seizure freedom was achieved in 83.3% of the cohort, and only 20.8% of the seizure-free patients, who were more likely to have undergone gross-total resection (p = 0.031), were able to discontinue antiepileptic drug use postoperatively. Preoperative seizures (OR 3.54, 95% CI 1.37-9.12, p = 0.009), recurrent tumors (OR 2.89, 95% CI 1.08-7.74, p = 0.035), and tumors requiring postoperative radiation (OR 2.82, 95% CI 1.09-7.33, p = 0.033) were significant predictors of postoperative seizures in a multivariate analysis.

Conclusions: Seizures are relatively common at meningioma presentation. While NF2-mutated tumors are significantly associated with preoperative seizures, the association appears to be mediated through edema and atypical histology. Patients who undergo radiation and/or have a recurrence are at risk for postoperative seizures, regardless of the extent of resection. Preoperative seizures may indeed portend a more potentially aggressive molecular entity and challenging clinical course with a higher risk of recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.7.JNS201042DOI Listing
December 2020

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

J Neurosurg 2019 Oct 25:1-10. Epub 2019 Oct 25.

19Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Objective: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts.

Methods: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features.

Results: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation.

Conclusions: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2019.8.JNS191266DOI Listing
October 2019

Bee pathogen transmission dynamics: deposition, persistence and acquisition on flowers.

Proc Biol Sci 2019 05 29;286(1903):20190603. Epub 2019 May 29.

2 Department of Biology, University of Massachusetts , Amherst, MA 01003 , USA.

Infectious diseases are a primary driver of bee decline worldwide, but limited understanding of how pathogens are transmitted hampers effective management. Flowers have been implicated as hubs of bee disease transmission, but we know little about how interspecific floral variation affects transmission dynamics. Using bumblebees ( Bombus impatiens), a trypanosomatid pathogen ( Crithidia bombi) and three plant species varying in floral morphology, we assessed how host infection and plant species affect pathogen deposition on flowers, and plant species and flower parts impact pathogen survival and acquisition at flowers. We found that host infection with Crithidia increased defaecation rates on flowers, and that bees deposited faeces onto bracts of Lobelia siphilitica and Lythrum salicaria more frequently than onto Monarda didyma bracts . Among flower parts, bracts were associated with the lowest pathogen survival but highest resulting infection intensity in bee hosts. Additionally, we found that Crithidia survival across flower parts was reduced with sun exposure. These results suggest that efficiency of pathogen transmission depends on where deposition occurs and the timing and place of acquisition, which varies among plant species and environmental conditions. This information could be used for development of wildflower mixes that maximize forage while minimizing disease spread.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rspb.2019.0603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545085PMC
May 2019

Trio Haploinsufficiency Causes Neurodevelopmental Disease-Associated Deficits.

Cell Rep 2019 03;26(10):2805-2817.e9

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA; Department of Neuroscience, Yale University, New Haven, CT 06510, USA. Electronic address:

Heterozygous coding mutations in TRIO are associated with neurodevelopmental disorders, including autism, schizophrenia, bipolar disorder, and epilepsy, and impair TRIO's biochemical activities. To model mutant alleles, we ablated one or both Trio alleles from excitatory neurons in the cortex and hippocampus of mice. Trio haploinsufficiency increases anxiety and impairs social preference and motor coordination. Trio loss reduces forebrain size and dendritic arborization but increases dendritic spine densities. Cortical synapses in Trio haploinsufficient mice are small, exhibit pre- and postsynaptic deficits, and cannot undergo long-term potentiation. Similar phenotypes are observed in Trio knockout mice. Overall, Trio haploinsufficiency causes severe disease-relevant deficits in behavior and neuronal structure and function. Interestingly, phosphodiesterase 4A5 (PDE4A5) levels are reduced and protein kinase A (PKA) signaling is increased when TRIO levels are reduced. Elevation of PDE4A5 and drug-based attenuation of PKA signaling rescue Trio haploinsufficiency-related dendritic spine defects, suggesting an avenue for therapeutic intervention for TRIO-related neurodevelopmental disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2019.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436967PMC
March 2019

Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks.

Elife 2018 04 26;7. Epub 2018 Apr 26.

Department of Cell Biology, Yale School of Medicine, New Haven, United States.

Poly(ADP ribose) polymerase inhibitors (PARPi) target cancer cells deficient in homology-directed repair of DNA double-strand breaks (DSBs). In preclinical models, PARPi resistance is tied to altered nucleolytic processing (resection) at the 5' ends of a DSB. For example, loss of either 53BP1 or Rev7/MAD2L2/FANCV derepresses resection to drive PARPi resistance, although the mechanisms are poorly understood. Long-range resection can be catalyzed by two machineries: the exonuclease Exo1, or the combination of a RecQ helicase and Dna2. Here, we develop a single-cell microscopy assay that allows the distinct phases and machineries of resection to be interrogated simultaneously in living cells. Using this assay, we find that the 53BP1 orthologue and Rev7 specifically repress long-range resection through the RecQ helicase-dependent pathway, thereby preventing hyper-resection. These results suggest that 'rewiring' of BRCA1-deficient cells to employ an Exo1-independent hyper-resection pathway is a driver of PARPi resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.33402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945276PMC
April 2018