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Ryan Smith

Publications and source records attributed to Ryan Smith.

11 recordsLinked to original sources
PubMed2026

EWAS in a polyphenol dense, DNA methylation-targeted, controlled diet and lifestyle study.

BACKGROUND: Dietary and lifestyle factors can influence DNA methylation patterns. We previously reported epigenetic age attenuation following a controlled study using an 8-week polyphenol-dense, DNA methylation-targeted diet and lifestyle intervention in healthy males (Methylation Diet and Lifestyle Study), with phytonutrient/polyphenol-rich foods (green tea, oolong tea, curcumin, garlic, and berries) being most predictive of this effect. METHODS: Here we conducted an epigenome-wide association study (EWAS) in 38 participants from the Methylation Diet and Lifestyle Study. The intervention included a dietary pattern intentionally rich in substrate and cofactor nutrients for methylation pathways, and components known to alter DNA-methyltransferase (DNMT) enzyme activity. In line with prior EWAS studies with small sample sizes where FDR-significant findings are unlikely, we used pre-specified nominal P-value thresholds (0.001, 0.0001) for the exploratory analyses. RESULTS: At P < 0.001 (unadjusted), 676 differentially methylated loci (DML) were identified in the intervention group versus 286 in controls. At P < 0.0001 (unadjusted), 50 DML were identified in the intervention group compared to 13 in controls. Fifteen DML were in transcription start site-proximal regions of genes including those involved in zinc homeostasis and nutrient sensing, development and pluripotency, proteostasis and genome stability, tumor suppression, and synaptic function. A group-by-time interaction analysis identified 70 intervention-specific DML at P < 0.0001, with nominal enrichment including autophagy, mTOR signaling, and chromatin remodeling pathways. A regional DMR analysis identified 128 within-group and 129 interaction-specific DMRs. DMR functional enrichment analyses revealed convergent nominal associations with lipid metabolism (alpha-linolenic acid, lipoic acid, biosynthesis of unsaturated fatty acids, PPAR signaling, cholesterol homeostasis), central energy metabolism (TCA cycle, glycolysis/gluconeogenesis, pentose phosphate, pyruvate), and nutrient sensing (PI3K-Akt, mTOR, AMPK, autophagy as well as other pathways). As expected for the limited cohort size and short intervention duration, none of the single CpG findings or enrichment analyses survived multiple test correction and are therefore considered exploratory and hypothesis-generating only. CONCLUSION: This EWAS identified a larger number of nominally changing CpGs in the intervention group compared to controls as well as biologically coherent methylation changes. These findings provide mechanistic hypotheses for previously observed epigenetic age attenuation. Replication in larger cohorts, longer intervention durations, and functional validation remain essential.

DNA methylation↗
PubMed2006

A multicenter study demonstrating discordant results from electronic prostate-specific antigen biochemical failure calculation systems.

PURPOSE: To evaluate the interobserver variation of four electronic biochemical failure (bF) calculators using three bF definitions. METHODS AND MATERIALS: The data of 1200 men were analyzed using the electronic bF calculators of four institutions. Three bF definitions were examined for their concordance of bF identification across the centers: the American Society for Therapeutic Radiology and Oncology consensus definition (ACD), the lowest prostate-specific antigen (PSA) level to date plus 2 ng/mL (L2), and a threshold of 3 ng/mL (T3). RESULTS: Unanimous agreement regarding bF status using the ACD, L2, and T3 definitions occurred in 87.3%, 96.4%, and 92.7% of cases, respectively. Using the ACD, 63% of the variation was from one institution, which allowed the bF status to be reversed if a PSA decline was seen after bF (PSA "bounce"). A total of 270 men had an ACD bF time variation of >2 months across the calculators, and the 5-year freedom from bF rate was 49.8-60.9%. The L2 definition had a 20.5% rate of calculated bF times; which varied by >2 months (median, 6.4; range, 2.1-75.6) and a corresponding 5-year freedom from bF rate of 55.9-61.0%. The T3 definition had a 2.0% range in the 5-year freedom from bF. Fifteen definition interpretation variations were identified. CONCLUSION: Reported bF results vary not only because of bF definition differences, but because of variations in how those definitions are written into computer-based calculators, with multiple interpretations most prevalent for the ACD. An algorithm to avoid misinterpretations is proposed for the L2 definition. A verification system to guarantee consistent electronic bF results requires development.

Databases, Factual↗
PubMed2006

Quality and content of abstracts in papers reporting about drug exposures during pregnancy.

BACKGROUND: Most clinicians read only the abstract of papers in scientific journals. Therefore, it is very important that abstracts contain as much information as possible, to summarize the data succinctly. Our objectives were to evaluate the quality of information in abstracts reporting human fetal outcomes following drug exposure during pregnancy. METHODS: We developed quality criteria based on previous work, modifying them for use with pregnancy outcomes. Quality scores were calculated as present/absent for all of the equally weighted criteria, then expressed as percentages (present/[present + absent]). We examined a random sample of 100 abstracts obtained through searches of MEDLINE, EMBASE, and the Web of Science databases from 1990 to 2005. Average quality scores were compared across designs (cohort, case-control, meta-analysis, and mixed design) Using Kruskal-Wallis ANOVA and structured/unstructured formats using Student's t test. RESULTS: The overall average quality was 59.2% +/- 14% (median, 61.5%; range, 15.4-83.3%). Quality was not significantly different across designs (P = .16) or between structured and unstructured abstracts (P = .44). Quality scores increased over time (Rho = 0.23, P = .02). Most frequently absent were baseline risk (94%), drug dose (91%), nonsignificant P values (72%), confounders (69%), significant P values (57%), and risk difference (48%). CONCLUSIONS: Abstracts provide insufficient information, particularly baseline risk values, for readers to make evidence-based decisions regarding drug use during pregnancy. Efforts need to be made to improve the quality of abstracts and include critical information such as baseline risk.

Abstracting and Indexing↗
PubMed2006

Childhood asthma and measles vaccine response.

BACKGROUND: Asthmatic patients have a TH2-predominant milieu that is associated with humoral immunity. However, little is known about whether humoral immune responses to viral antigens differ between asthmatic and nonasthmatic children. OBJECTIVE: To determine whether humoral immune response differs in asthmatic patients vs nonasthmatic patients. METHODS: Measles virus specific IgG antibody levels were determined for the Rochester Family Measles Study cohort (n = 876), a convenience sample of healthy children 5 to 12 years of age in Rochester, MN. We conducted comprehensive medical record reviews of 838 children who were eligible for this study. We determined the child's asthma status at the time of determination of antibody levels by applying predetermined criteria for asthma. Comparisons were made using the 2-sample t test or chi2 test. RESULTS: Of the 838 children, 156 (18.6%) had asthma at the time of the determination of antibody levels and were not taking systemic steroids within 14 days of specimen collection. Among those with a nonequivocal antibody reading, the seropositive response rates were similar in asthmatic patients and nonasthmatic patients (89.7% vs 90.3%, respectively; P = .83). However, the equivocal response rates were slightly higher among asthmatic patients than nonasthmatic patients (6.4% vs 4.7%, respectively). CONCLUSION: Asthmatic children seem to have similar humoral immune responses to measles vaccine as those without asthma. Although the findings reassure health care practitioners, whether this finding is generalizable to other vaccines and whether asthmatic patients with low antibody levels have normal cell-mediated immunity need to be elucidated in future studies.

Antibody Formation↗
PubMed2005

Comparison of manual vs. automated multimodality (CT-MRI) image registration for brain tumors.

Computed tomgoraphy-magnetic resonance imaging (CT-MRI) registrations are routinely used for target-volume delineation of brain tumors. We clinically use 2 software packages based on manual operation and 1 automated package with 2 different algorithms: chamfer matching using bony structures, and mutual information using intensity patterns. In all registration algorithms, a minimum of 3 pairs of identical anatomical and preferably noncoplanar landmarks is used on each of the 2 image sets. In manual registration, the program registers these points and links the image sets using a 3-dimensional (3D) transformation. In automated registration, the 3 landmarks are used as an initial starting point and further processing is done to complete the registration. Using our registration packages, registration of CT and MRI was performed on 10 patients. We scored the results of each registration set based on the amount of time spent, the accuracy reported by the software, and a final evaluation. We evaluated each software program by measuring the residual error between "matched" points on the right and left globes and the posterior fossa for fused image slices. In general, manual registration showed higher misalignment between corresponding points compared to automated registration using intensity matching. This error had no directional dependence and was, most of the time, larger for a larger structure in both registration techniques. Automated algorithm based on intensity matching also gave the best results in terms of registration accuracy, irrespective of whether or not the initial landmarks were chosen carefully, when compared to that done using bone matching algorithm. Intensity-matching algorithm required the least amount of user-time and provided better accuracy.

Algorithms↗
PubMed2004

Pictures, progress, and perplexities: the immediate cell biological effects of ionizing radiation.

An unexpected image made by an invisible beam precipitated the discovery of X-rays in the waning days of the 19th century. The usefulness and dangers of this new discovery soon became clear, emphasizing the importance of DNA damage recognition and repair after exposure to ionizing radiation (IR). One hundred years later, new images of the immediate effects of ionizing radiation have once again ignited excitement among investigators. The combination of advanced imaging techniques with new reagents targeting molecular components of the cellular DNA damage response have enabled visualization of sites of DNA damage, resulting in fresh insights into the immediate cell biological effects of IR. This review will review these advances, highlighting recent progress as well as critical questions that remain unanswered.

Apoptosis↗
PubMed2004

Age dependency of cartilage magnetic resonance imaging T2 relaxation times in asymptomatic women.

OBJECTIVE: Because the magnetic resonance imaging (MRI) transverse relaxation time (T2) of cartilage is sensitive to organization of collagen fibers in the cartilage, it may be a noninvasive image marker for senescent changes in cartilage collagen and early cartilage degeneration. The purpose of this study was to determine age-dependent differences in cartilage T2 values in healthy asymptomatic women. METHODS: Quantitative T2 maps of patellar cartilage from 30 asymptomatic women ages 22-86 years were obtained using a 3.0T MRI scanner. The study population was stratified by age into 4 cohorts: 18-30, 31-45, 46-65, and 66-86 years. Spatial differences in cartilage T2 were determined as a function of normalized distance from bone. Older groups were compared with the 18-30-year-old group to determine the effects of age on cartilage T2 values. Regions were considered statistically significantly different if the mean T2 values between groups differed at P < 0.05. RESULTS: Mean cartilage T2 profiles were nearly identical for the 2 youngest cohorts. Compared with the 18-30-year-old group, T2 values were statistically significantly longer in the superficial 40% of cartilage in the 46-65-year-old group and over the entire cartilage thickness in the 66-86-year-old group. CONCLUSION: The location of T2 elevations in women over the age of 45 years is consistent with the theory that senescent changes of cartilage collagen begin near the articular surface and progress to the deeper cartilage with advancing age.

Adolescent↗
PubMed2003

Analysis and optimization of structure-based virtual screening protocols. (3). New methods and old problems in scoring function design.

Scoring function research remains a primary focus of current structure-based virtual screening (SVS) technology development. Here, we present an alternative method for scoring function design that attempts to combine crystallographic structural information with data derived from directly within SVS calculations. The technique utilizes a genetic algorithm (GA) to optimize functions based on binding property data derived from multiple virtual screening calculations. These calculations are undertaken on protein data bank (PDB) complex active sites using ligands of known binding mode in conjunction with "noise" compounds. The advantages of such an approach are that the function does not rely on assay data and that it can potentially use the "noise" binding data to recognize the sub-optimal docking interactions inherent in SVS calculations. Initial efforts in technique exploration using DOCK are presented, with comparisons made to existing DOCK scoring functions. An analysis of the problems inherent to scoring function development is also made, including issues in dataset creation and limitations in descriptor utility when viewed from the perspective of docking mode resolution. The future directions such studies might take are also discussed in detail.

Algorithms↗