David Rotter

Evolution of novel O-methyltransferases from the Vanilla planifolia caffeic acid O-methyltransferase.

The biosynthesis of many plant secondary compounds involves the methylation of one or more hydroxyl groups, catalyzed by O-methyltransferases (OMTs). Here, we report the characterization of two OMTs, Van OMT-2 and Van OMT-3, from the orchid Vanilla planifolia Andrews. These enzymes catalyze the methylation of a single outer hydroxyl group in substrates possessing a 1,2,3-trihydroxybenzene moiety, such as methyl gallate and myricetin. This is a substrate requirement not previously reported for any OMTs. Based on sequence analysis these enzymes are most similar to caffeic acid O-methyltransferases (COMTs), but they have negligible activity with typical COMT substrates. Seven of 12 conserved substrate-binding residues in COMTs are altered in Van OMT-2 and Van OMT-3. Phylogenetic analysis of the sequences suggests that Van OMT-2 and Van OMT-3 evolved from the V. planifolia COMT. These V. planifolia OMTs are new instances of COMT-like enzymes with novel substrate preferences.

Velvet bentgrass (Agrostis canina L.) is the likely ancestral diploid maternal parent of allotetraploid creeping bentgrass (Agrostis stolonifera L.)

Understanding genetic relationships among the three most important Agrostis species will be important in breeding and genomic studies aimed at cultivar improvement. Creeping, colonial, and velvet bentgrasses (Agrostis stolonifera L., A. capillaris L., and A. canina L., respectively) are commercially important turfgrass species often used on golf courses. Velvet bentgrass is a diploid and creeping and colonial bentgrasses are both allotetraploids. A model for the genomic relationships among these species was previously developed from cytological evidence. The genome designations were A1A1 for velvet bentgrass, A1A1A2A2 for colonial bentgrass, and A2A2A3A3 for creeping bentgrass. Here we used phylogenetic analysis based on DNA sequences of nuclear ITS and protein coding genes and the plastid trnK intron and matK gene to reexamine these relationships. In contrast to the previous model, the DNA sequence analysis suggested that velvet bentgrass was closely related to creeping bentgrass and it is likely the maternal parent of creeping bentgrass. Phylogenetic analysis of some conserved nuclear genes revealed a close relationship of the velvet bentgrass sequences with the A2 subgenome sequences of creeping bentgrass. We therefore propose that velvet bentgrass be designated as having the A2 genome, rather than the A1 genome as in the previous model.

Validation of a Contemporary Five-tiered Gleason Grade Grouping Using Population-based Data

This population-based study assesses whether a proposed five-tiered Gleason grade grouping (GGG) system predicts prostate cancer-specific mortality (PCSM). Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 331320 prostate cancer patients who had primary and secondary Gleason patterns diagnosed between January 2006 and December 2012. We used the Fine and Gray proportional hazards model for subdistributions and the corresponding cumulative incidence to quantify the risk of PCSM. We found that the risk of PCSM approximately doubled with each GGG increase. Among men who underwent radical prostatectomy and using GGG1 (Gleason score ≤6) as the reference group, the adjusted hazard ratio for PCSM was 1.13 (95% confidence interval [CI] 0.83-1.54) for GGG2, 1.87 (95% CI 1.33-2.65) for GGG3, 5.03 (95% CI 3.59-7.06) for GGG4, and 10.92 (CI 8.03-14.84) for GGG5. Similar patterns were observed regardless of the type of primary cancer treatment received or clinical stage. In summary, our study, with large, racially diverse populations that reflect real world experiences, demonstrates that the new five-tiered GGG system predicts PCSM well regardless of treatment received or clinical stage at diagnosis.nnnPATIENT SUMMARYnIn this report we examined prostate cancer mortality using the new five-tiered cancer grading system using data for a large US population. We found that the new five-tiered cancer grading system can predict prostate cancer-specific mortality well, regardless of the type of primary cancer treatment and clinical stage. We conclude that this new five-tiered cancer grading system is useful in guiding treatment decisions.

Dideoxy polymorphism scanning, a gene-based method for marker development for genetic linkage mapping

One of the fastest growing areas of biotechnology research today is marker-assisted breeding of crops. As a prerequisite to marker assisted breeding, genetic linkage maps are currently being developed for many species. For many purposes gene-based markers are the marker type of choice. The biggest problem in genetic linkage mapping using gene-based markers is the identification of polymorphisms between the parents of the population. To improve the efficiency of marker generation, we have developed a simple, and reasonable-cost method of polymorphism detection termed dideoxy polymorphism scanning. Since most of the time required to develop a gene-based linkage map is spent in identification of useful polymorphisms, this method will significantly shorten the time required for map generation and therefore reduce the overall cost.

Impact of Patient–Provider Race, Ethnicity, and Gender Concordance on Cancer Screening: Findings from Medical Expenditure Panel Survey

Background: Racial and ethnic minorities experience lower rates of cancer screening compared with non-Hispanic whites (NHWs). Previous studies evaluating the role of patient–provider race, ethnicity, or gender concordance in cancer screening have been inconclusive. Methods: In a cross-sectional analysis using the Medical Expenditure Panel Survey (MEPS), data from 2003 to 2010 were assessed for associations between patient–provider race, ethnicity, and/or gender concordance and, screening (American Cancer Society guidelines) for breast, cervical, and colorectal cancer. Multivariable logistic analyses were conducted to examine associations of interest. Results: Of the 32,041 patient–provider pairs in our analysis, more than 60% of the patients were NHW, 15% were non-Hispanic black (NHB), and 15% were Hispanic. Overall, patients adherent to cancer screening were more likely to be non-Hispanic, better educated, married, wealthier, and privately insured. Patient–provider gender discordance was associated with lower rates of breast [OR, 0.83; 95% confidence interval (CI), 0.76–0.90], cervical (OR, 0.83; 95% CI, 0.76–0.91), and colorectal cancer (OR, 0.84; 95% CI, 0.79–0.90) screening in all patients. This association was also significant after adjusting for racial and/or ethnic concordance. Conversely, among NHWs and NHBs, patient–provider racial and/or ethnic concordance was not associated with screening. Among Hispanics, patient–provider ethnic discordant pairs had higher breast (58% vs. 52%) and colorectal cancer (45% vs. 39%) screening rates compared with concordant pairs. Conclusions: Patient–provider gender concordance positively affected cancer screening. Patient–provider ethnic concordance was inversely associated with receipt of cancer screening among Hispanics. This counter-intuitive finding requires further study. Impact: Our findings highlight the importance of gender concordance in improving cancer screening rates. Cancer Epidemiol Biomarkers Prev; 26(12); 1804–11. ©2017 AACR.

Differential and Joint Effects of Metformin and Statins on Overall Survival of Elderly Patients with Pancreatic Adenocarcinoma: A Large Population-Based Study.

Background: Published evidence indicates that individual use of metformin and statin is associated with reduced cancer mortality. However, their differential and joint effects on pancreatic cancer survival are inconclusive. Methods: We identified a large population-based cohort of 12,572 patients ages 65 years or older with primary pancreatic ductal adenocarcinoma (PDAC) diagnosed between 2008 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files. Cox proportional hazards models with time-varying covariates adjusted for propensity scores were used to assess the association while controlling for potential confounders. Results: Of 12,572 PDAC patients, 950 (7.56%) had used metformin alone, 4,506 (35.84%) had used statin alone, and 2,445 (19.45%) were dual users. Statin use was significantly associated with improved overall survival [HR, 0.94; 95% confidence interval (CI), 0.90–0.98], and survival was more pronounced in postdiagnosis statin users (HR, 0.69; 95% CI, 0.56–0.86). Metformin use was not significantly associated with overall survival (HR, 1.01; 95% CI, 0.94–1.09). No beneficial effect was observed for dual users (HR, 1.00; 95% CI, 0.95–1.05). Conclusions: Our findings suggest potential benefits of statins on improving survival among elderly PDAC patients; further prospective studies are warranted to corroborate the putative benefit of statin therapy in pancreatic cancer. Impact: Although more studies are needed to confirm our findings, our data add to the body of evidence on potential anticancer effects of statins. Cancer Epidemiol Biomarkers Prev; 26(8); 1225–32. ©2017 AACR.

Emotional processing during psychotherapy among women newly diagnosed with a gynecological cancer

OBJECTIVEnOur aim was to compare changes in emotional processing by women newly diagnosed with gynecological cancer enrolled in either a coping and communication skills intervention (CCI) or a supportive counseling (SC) intervention. We examined the association between in-session emotional processing and patient-rated therapeutic progress.nnnMETHODnThree therapy sessions with 201 patients were rated for the depth of emotional processing (peak and mode) during emotion episodes (EEs) using the Experiencing Rating Scale (EXP). Participants completed measures of dispositional emotional expressivity, depressive symptoms, and cancer-related distress before treatment began, as well as ratings of perceived progress in therapy after each session.nnnRESULTSnPeak EXP ratings averaged between 2.7 and 3.1, indicating that women discussed events, their emotional reactions, and their private experiences in sessions. A small proportion of patients had high levels of processing, indicating deeper exploration of the meaning of their feelings and experiences. Women in SC were able to achieve a higher level of emotional processing during the middle and later sessions, and during cancer-related EEs in the later session. However, emotional processing was not significantly associated with a patients perceived therapeutic progress with SC. In the CCI group, higher levels of emotional processing were associated with greater session progress, suggesting that it may play an important role in patient-rated treatment outcomes.nnnSIGNIFICANCE OF RESULTSnNewly diagnosed gynecological cancer patients are able to attend to their emotions and personal experiences, particularly when discussing cancer-related issues during both short-term SC and prescriptive coping skills interventions.

Receipt of recommended surveillance with imaging in elderly survivors of early stage non-small cell lung cancer

PURPOSEnEarly-stage lung cancer survivorsremain at high risk for recurrence or second cancers. We measured the rates and determinants of regular surveillance imaging in early-stage non-small cell lung cancer (NSCLC) survivors.nnnMETHODSnPatients (diagnosed 2001-2011) with resected stage I and II NSCLC were identified from the Surveillance Epidemiology and End Results (SEER)-Medicare linked database. Patients were censored at recurrence/second cancer diagnosis, loss to follow-up or death. Receipt of a scan during the surveillance periods of 7-18, 19-30, 31-42 and 43-60 months from date of surgery was assessed.nnnRESULTSnOf 10,680 survivors assessed during the 18-month surveillance period, 71% received imaging in first 18 months. Only 56% and 43% continued to receive regular imaging by 30-month and 60-month of follow-up, respectively. Survivors were less likely to receive imaging if they were older, black, unmarried, received no adjuvant therapy, had stage I disease (vs. stage II) or were diagnosed before 2006. In adjusted analysis, survivors who received recommended imaging up to 18 months from surgery experienced better survival compared to survivors who did not (HR 0.92; 95% CI 0.85-0.99). Survival benefit was also observed in survivors who underwent regular imaging up to 5 years from surgery (HR 0.68; 95% CI 0.60-0.78).nnnCONCLUSIONSnMore than half the lung cancer survivors received less than the recommended long-term surveillance imaging. Long-term adherence to surveillance is associated with improved survival. Our study provides evidence to support the current clinical guidelines for surveillance for lung cancer survivors that are primarily consensus-based at present.

PROMIS Peer Relationships Short Form: How Well Does Self-Report Correlate With Data From Peers?

ObjectivenTo examine the psychometric properties of the Patient-Reported Outcomes Measurement Information System (PROMIS®) peer relationships short form (PR-SF), including association with peer-reported friendships, likeability, and social reputation.nnnMethodn203 children (Mageu2009=u200910.12u2009years, SDu2009=u20092.37, rangeu2009=u20096-14) in Grades 1-8 completed the 8-item PR-SF and friendship nominations, like ratings, and social reputation measures about their peers during 2 classroom visits approximately 4u2009months apart, as part of a larger study. A confirmatory factor analysis, followed by an exploratory factor analysis, was conducted to examine the factor structure of the PR-SF. Spearman correlations between the PR-SF and peer-reported outcomes evaluated construct validity.nnnResultsnFor the PR-SF, a 2-factor solution demonstrated better fit than a 1-factor solution. The 2 factors appear to assess friendship quality (3 items) and peer acceptance (5 items). Reliability was marginal for the friendship quality factor (.66) but adequate for the acceptance factor (.85); stability was .34 for the PR-SF over 4u2009months. The PR-SF (8 items) and acceptance factor (5 items) both had modest but significant correlations with measures of friendship (rs =u2009.25-.27), likeability (rsu2009=u2009.21-.22), and social reputation (rsu2009=u2009.29-.44).nnnConclusionsnThe PR-SF appears to be measuring two distinct aspects of social functioning. The 5-item peer acceptance scale is modestly associated with peer-reported friendship, likeability, and social reputation. Although not a replacement for peer-reported outcomes, the PR-SF is a promising patient-reported outcome for peer relationships in youth.

Factors associated with high-risk human papillomavirus test utilization and infection: a population-based study of uninsured and underinsured women

BackgroundCurrent cervical cancer screening guidelines recommend a Pap test every 3xa0years for women age 21–65xa0years, or for women 30–65xa0years who want to lengthen the screening interval, a combination of Pap test and high-risk human papilloma virus testing (co-testing) every 5xa0years. Little population-based data are available on human papilloma virus test utilization and human papilloma virus infection rates. The objective of this study was to examine the patient-level, cervical cancer screening, and area-level factors associated with human papilloma virus testing and infection among a diverse sample of uninsured and underinsured women enrolled in the New Jersey Cancer Early Education and Detection (NJCEED) Program.MethodsWe used data for a sample of 50,510 uninsured/underinsured women, ageu2009≥u200929xa0years, who screened for cervical cancer through NJCEED between January 1, 2009 and December 31, 2015. Multivariable logistic regression models were used to estimate associations between ever having a human papilloma virus test or a positive test result, and individual- (age, race/ethnicity, birthplace) and area-level covariates (% below federal poverty level, % minority, % uninsured), and number of screening visits.ResultsOnly 26.6% (13,440) of the sample had at least one human papilloma virus test. Among women who underwent testing, 13.3% (1792) tested positive for human papilloma virus. Most women who were positive for human papilloma virus (99.4%) had their first test as a co-test. Human papilloma virus test utilization and infection were significantly associated with age, race/ethnicity, birthplace (country), and residential area-level poverty. Rates of human papilloma virus testing and infection also differed significantly across counties in the state of New Jersey.ConclusionsThese findings suggest that despite access to no-cost cervical cancer screening for eligible women, human papilloma virus test utilization was relatively low among diverse, uninsured and underinsured women in New Jersey, and test utilization and infection were associated with individual-level and area-level factors.