Karan P. Singh

Text and Structural Data Mining of Influenza Mentions in Web and Social Media

Text and structural data mining of web and social media (WSM) provides a novel disease surveillance resource and can identify online communities for targeted public health communications (PHC) to assure wide dissemination of pertinent information. WSM that mention influenza are harvested over a 24-week period, 5 October 2008 to 21 March 2009. Link analysis reveals communities for targeted PHC. Text mining is shown to identify trends in flu posts that correlate to real-world influenza-like illness patient report data. We also bring to bear a graph-based data mining technique to detect anomalies among flu blogs connected by publisher type, links, and user-tags.

Resveratrol Induces Growth Arrest and Apoptosis through Activation of FOXO Transcription Factors in Prostate Cancer Cells

Background Resveratrol, a naturally occurring phytopolyphenol compound, has attracted extensive interest in recent years because of its diverse pharmacological characteristics. Although resveratrol possesses chemopreventive properties against several cancers, the molecular mechanisms by which it inhibits cell growth and induces apoptosis have not been clearly understood. The present study was carried out to examine whether PI3K/AKT/FOXO pathway mediates the biological effects of resveratrol. Methodology/Principal Findings Resveratrol inhibited the phosphorylation of PI3K, AKT and mTOR. Resveratrol, PI3K inhibitors (LY294002 and Wortmannin) and AKT inhibitor alone slightly induced apoptosis in LNCaP cells. These inhibitors further enhanced the apoptosis-inducing potential of resveratrol. Overexpression of wild-type PTEN slightly induced apoptosis. Wild type PTEN and PTEN-G129E enhanced resveratrol-induced apoptosis, whereas PTEN-G129R had no effect on proapoptotic effects of resveratrol. Furthermore, apoptosis-inducing potential of resveratrol was enhanced by dominant negative AKT, and inhibited by wild-type AKT and constitutively active AKT. Resveratrol has no effect on the expression of FKHR, FKHRL1 and AFX genes. The inhibition of FOXO phosphorylation by resveratrol resulted in its nuclear translocation, DNA binding and transcriptional activity. The inhibition of PI3K/AKT pathway induced FOXO transcriptional activity resulting in induction of Bim, TRAIL, p27/KIP1, DR4 and DR5, and inhibition of cyclin D1. Similarly, resveratrol-induced FOXO transcriptional activity was further enhanced when activation of PI3K/AKT pathway was blocked. Over-expression of phosphorylation deficient mutants of FOXO proteins (FOXO1-TM, FOXO3A-TM and FOXO4-TM) induced FOXO transcriptional activity, which was further enhanced by resveratrol. Inhibition of FOXO transcription factors by shRNA blocked resveratrol-induced upregulation of Bim, TRAIL, DR4, DR5, p27/KIP1 and apoptosis, and inhibition of cyclin D1 by resveratrol. Conclusion/Significance These data suggest that FOXO transcription factors mediate anti-proliferative and pro-apoptotic effects of resveratrol, in part due to activation of extrinsic apoptosis pathway.

Zero-Inflated Generalized Poisson Regression Model with an Application to Domestic Violence Data

The generalized Poisson regression model has been used to model dispersed count data. It is a good competitor to the negative binomial re- gression model when the count data is over-dispersed. Zero-inflated Poisson and zero-inflated negative binomial regression models have been proposed for the situations where the data generating process results into too many zeros. In this paper, we propose a zero-inflated generalized Poisson (ZIGP) regression model to model domestic violence data with too many zeros. Es- timation of the model parameters using the method of maximum likelihood is provided. A score test is presented to test whether the number of zeros is too large for the generalized Poisson model to adequately fit the domestic violence data.

Resveratrol Enhances Antitumor Activity of TRAIL in Prostate Cancer Xenografts through Activation of FOXO Transcription Factor

Background Resveratrol (3, 4′, 5 tri-hydroxystilbene), a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer. Methodology/Principal Findings Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining) and inducing apoptosis (TUNEL staining). The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27/K IP1, and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells) and markers of metastasis (MMP-2 and MMP-9). The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity. Conclusions/Significance These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer.

Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes : a South-Eastern cancer study group (SEG) trial

In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of > or = four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes.

The Evaluation of School‐Based Violence Prevention Programs: A Meta‐Analysis*

BACKGROUND Youth violence and related aggressive behaviors have become serious public health issues with physical, economic, social, and psychological impacts and consequences. This study identified and evaluated the characteristics of successful school-based violence prevention programs. METHODS Twenty-six randomized controlled trial (RCT), school-based studies that were designed to reduce externalizing, aggressive, and violent behavior between the 1st and 11th grades were analyzed for assessing the effects of 5 program characteristics by comparing results of intervention groups to control groups (no intervention) after intervention using a meta-analysis. Electronic databases and bibliographies were systematically searched, and a standardized mean difference was used for analysis. RESULTS There was no significant difference between interventions, although programs that used non-theory-based interventions, focused on at-risk and older children, and employed intervention specialists had slightly stronger effects in reducing aggression and violence. Interventions using a single approach had a mild positive effect on decreasing aggressive and violent behavior (effect size =-0.15, 95% CI =-0.29 to -0.02, p = .03). CONCLUSIONS Unlike previous individual study findings, this meta-analysis did not find any differential effects for 4 of the 5 program characteristics. In addition, the significant effect noted was contrary to expectation, exemplifying the complexity of identifying effective program strategies. This study adds to the current literature by assessing the program characteristics of RCT studies in an effort to determine what factors may affect school-based violence prevention program success.

Osteopathic Manual Treatment and Ultrasound Therapy for Chronic Low Back Pain: A Randomized Controlled Trial

PURPOSE We studied the efficacy of osteopathic manual treatment (OMT) and ultrasound therapy (UST) for chronic low back pain. METHODS A randomized, double-blind, sham-controlled, 2 × 2 factorial design was used to study OMT and UST for short-term relief of nonspecific chronic low back pain. The 455 patients were randomized to OMT (n = 230) or sham OMT (n = 225) main effects groups, and to UST (n = 233) or sham UST (n = 222) main effects groups. Six treatment sessions were provided over 8 weeks. Intention-to-treat analysis was performed to measure moderate and substantial improvements in low back pain at week 12 (30% or greater and 50% or greater pain reductions from baseline, respectively). Five secondary outcomes, safety, and treatment adherence were also assessed. RESULTS There was no statistical interaction between OMT and UST. Patients receiving OMT were more likely than patients receiving sham OMT to achieve moderate (response ratio [RR] = 1.38; 95% CI, 1.16-1.64; P <.001) and substantial (RR = 1.41, 95% CI, 1.13-1.76; P = .002) improvements in low back pain at week 12. These improvements met the Cochrane Back Review Group criterion for a medium effect size. Back-specific functioning, general health, work disability specific to low back pain, safety outcomes, and treatment adherence did not differ between patients receiving OMT and sham OMT. Nevertheless, patients in the OMT group were more likely to be very satisfied with their back care throughout the study (P <.001). Patients receiving OMT used prescription drugs for low back pain less frequently during the 12 weeks than did patients in the sham OMT group (use ratio = 0.66, 95% CI, 0.43-1.00; P = .048). Ultrasound therapy was not efficacious. CONCLUSIONS The OMT regimen met or exceeded the Cochrane Back Review Group criterion for a medium effect size in relieving chronic low back pain. It was safe, parsimonious, and well accepted by patients.

GANT-61 inhibits pancreatic cancer stem cell growth in vitro and in NOD/SCID/IL2R gamma null mice xenograft

Multiple lines of evidence suggest that the Sonic Hedgehog (Shh) signaling pathway is aberrantly reactivated in pancreatic cancer stem cells (CSCs). The objectives of this study were to examine the molecular mechanisms by which GANT-61 (Gli transcription factor inhibitor) regulates stem cell characteristics and tumor growth. Effects of GANT-61 on CSCs viability, spheroid formation, apoptosis, DNA-binding and transcriptional activities, and epithelial-mesenchymal transition (EMT) were measured. Humanized NOD/SCID/IL2R gamma(null) mice were used to examine the effects of GANT-61 on CSCs tumor growth. GANT-61 inhibited cell viability, spheroid formation, and Gli-DNA binding and transcriptional activities, and induced apoptosis by activation of caspase-3 and cleavage of Poly-ADP ribose Polymerase (PARP). GANT-61 increased the expression of TRAIL-R1/DR4, TRAIL-R2/DR5 and Fas, and decreased expression of PDGFRα and Bcl-2. GANT-61 also suppressed EMT by up-regulating E-cadherin and inhibiting N-cadherin and transcription factors Snail, Slug and Zeb1. In addition, GANT-61 inhibited pluripotency maintaining factors Nanog, Oct4, Sox-2 and cMyc. Suppression of both Gli1 plus Gli2 by shRNA mimicked the changes in cell viability, spheroid formation, apoptosis and gene expression observed in GANT-61-treated pancreatic CSCs. Furthermore, GANT-61 inhibited CSC tumor growth which was associated with up-regulation of DR4 and DR5 expression, and suppression of Gli1, Gli2, Bcl-2, CCND2 and Zeb1 expression in tumor tissues derived from NOD/SCID IL2Rγ null mice. Our data highlight the importance of Shh pathway for self-renewal and metastasis of pancreatic CSCs, and also suggest Gli as a therapeutic target for pancreatic cancer in eliminating CSCs.

High blood pressure in school children: prevalence and risk factors

BackgroundThe purpose of this study was to determine the prevalence of high blood pressure (HBP) and associated risk factors in school children 8 to 13 years of age.MethodsElementary school children (n = 1,066) were examined. Associations between HBP, body mass index (BMI), gender, ethnicity, and acanthosis nigricans (AN) were investigated using a school based cross-sectional study. Blood pressure was measured and the 95th percentile was used to determine HBP. Comparisons between children with and without HBP were utilized. The crude and multiple logistic regression adjusted odds ratios were used as measures of association.ResultsFemales, Hispanics, overweight children, and children with AN had an increased likelihood of HBP. Overweight children (BMI ≥ 85th percentile) and those with AN were at least twice as likely to present with HBP after controlling for confounding factors.ConclusionTwenty one percent of school children had HBP, especially the prevalence was higher among the overweight and Hispanic group. The association identified here can be used as independent markers for increased likelihood of HBP in children.

On the Generalized Poisson Regression Model with an Application to Accident Data

In this paper a random sample of drivers aged sixty-five years or older was selected from the Alabama Department of Public Safety Records. The data in the sample has information on many variables including the number of accidents, demographic information, driving habits, and medication. The purpose of the sample was to assess the effects of demographic factors, driving habits, and medication use on elderly drivers. The generalized Poisson regression (GPR) model is considered for identifying the relationship between the number of accidents and some covariates. About 59% of drivers who rate their quality of driving as average or below are involved in automobile accidents. Drivers who take calcium channel blockers show a significantly reduced risk of about 34.5%. Based on the test for the dispersion parameter and the goodness-of-fit measure for the accident data, the GPR model performs as good as or better than the other regression models.