Complex chromosomal rearrangements by single catastrophic pathogenesis in NUT midline carcinoma

Lee, J.-K.,Louzada, S.,An, Y.,Kim, S. Y.,Kim, S.,Youk, J.,Park, S.,Koo, S. H.,Keam, B.,Jeon, Y. K.,Ku, J.-L.,Yang, F.,Kim, T. M.,Ju, Y. S. Oxford University Press 2017 Annals of Oncology Vol.28 No.4

<P><B>Background</B></P><P>Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic <I>BRD3/4–NUT</I> rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored.</P><P><B>Patients and methods</B></P><P>We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence <I>in situ</I> hybridization and using individual fluorescence probes.</P><P><B>Results</B></P><P>Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the <I>BRD3/4–NUT</I> oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple <I>BRD3/4–NUT</I> fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the <I>BRD4–NUT</I> rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%−75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells.</P><P><B>Conclusion</B></P><P>Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.</P>

Cure rate proportional odds models with spatial frailties for interval-censored data

Yiqi, Bao,Cancho, Vicente Garibay,Louzada, Francisco,Suzuki, Adriano Kamimura The Korean Statistical Society 2017 Communications for statistical applications and me Vol.24 No.6

This paper presents proportional odds cure models to allow spatial correlations by including spatial frailty in the interval censored data setting. Parametric cure rate models with independent and dependent spatial frailties are proposed and compared. Our approach enables different underlying activation mechanisms that lead to the event of interest; in addition, the number of competing causes which may be responsible for the occurrence of the event of interest follows a Geometric distribution. Markov chain Monte Carlo method is used in a Bayesian framework for inferential purposes. For model comparison some Bayesian criteria were used. An influence diagnostic analysis was conducted to detect possible influential or extreme observations that may cause distortions on the results of the analysis. Finally, the proposed models are applied for the analysis of a real data set on smoking cessation. The results of the application show that the parametric cure model with frailties under the first activation scheme has better findings.

Application of the Weibull-Poisson long-term survival model

Vigas, Valdemiro Piedade,Mazucheli, Josmar,Louzada, Francisco The Korean Statistical Society 2017 Communications for statistical applications and me Vol.24 No.4

In this paper, we proposed a new long-term lifetime distribution with four parameters inserted in a risk competitive scenario with decreasing, increasing and unimodal hazard rate functions, namely the Weibull-Poisson long-term distribution. This new distribution arises from a scenario of competitive latent risk, in which the lifetime associated to the particular risk is not observable, and where only the minimum lifetime value among all risks is noticed in a long-term context. However, it can also be used in any other situation as long as it fits the data well. The Weibull-Poisson long-term distribution is presented as a particular case for the new exponential-Poisson long-term distribution and Weibull long-term distribution. The properties of the proposed distribution were discussed, including its probability density, survival and hazard functions and explicit algebraic formulas for its order statistics. Assuming censored data, we considered the maximum likelihood approach for parameter estimation. For different parameter settings, sample sizes, and censoring percentages various simulation studies were performed to study the mean square error of the maximum likelihood estimative, and compare the performance of the model proposed with the particular cases. The selection criteria Akaike information criterion, Bayesian information criterion, and likelihood ratio test were used for the model selection. The relevance of the approach was illustrated on two real datasets of where the new model was compared with its particular cases observing its potential and competitiveness.

A Field Deployable Real-Time Loop-Mediated Isothermal Amplification Targeting Five Copy nrdB Gene for the Detection of ‘Candidatus Liberibacter asiaticus’ in Citrus

Tirumalareddy Danda,Jong-Won Park,Kimberly L. Timmons,Mamoudou Sétamou,Eliezer S. Louzada,Madhurababu Kunta 한국식물병리학회 2023 Plant Pathology Journal Vol.39 No.4

Huanglongbing (HLB) is one of the most destructive diseases in citrus, which imperils the sustainability of citriculture worldwide. The presumed causal agent of HLB, ‘Candidatus Liberibacter asiaticus’ (CLas) is a non-culturable phloem-limited α-proteobacterium transmitted by Asian citrus psyllids (ACP, Diaphorina citri Kuwayama). A widely adopted method for HLB diagnosis is based on quantitative real-time polymerase chain reaction (qPCR). Although HLB diagnostic qPCR provides high sensitivity and good reproducibility, it is limited by time-consuming DNA preparation from plant tissue or ACP and the requirement of proper lab instruments including a thermal cycler to conduct qPCR. In an attempt to develop a quick assay that can be deployed in the field for CLas detection, we developed a real-time loop-mediated isothermal amplification (rt-LAMP) assay by targeting the CLas five copy nrdB gene. The rt-LAMP assay using various plant sample types and psyllids successfully detected the nrdB target as low as ~2.6 Log10 copies. Although the rt-LAMP assay was less sensitive than laboratorybased qPCR (detection limit ~10 copies), the data obtained with citrus leaf and bark and ACP showed that the rt-LAMP assay has >96% CLas detection rate, compared to that of laboratory-based qPCR. However, the CLas detection rate in fibrous roots was significantly decreased compared to qPCR due to low CLas titer in some root DNA sample. We also demonstrated that the rt-LAMP assay can be used with a crude leaf DNA extract which is fully deployable in the field for quick and reliable HLB screening.

Chemical Composition and Antioxidant and Antimycobacterial Activities of Bromelia balansae (Bromeliaceae)

Roberta Gomes Coelho,Neli Kika Honda,Maria do Carmo Vieira,Rosenei Louzada Brum,Fernando Roge´rio Pavan,Clarice Queico Fujimura Leite,Claudia Andre´a Lima Cardoso 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.5

Bromelia balansae (Family Bromeliaceae) is a medicinal plant commonly used in the central region of Brazil as a cough syrup and also eaten roasted. The methanolic extract of ripe fruits was analyzed by chromatographic methods and spectrometrically. Four glycoside flavonols were isolated: kaempferol-3-O-α-l-rhamnopyranoside (1), kaempferol-3-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (2), quercetin-3-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (3), and kaempferol 3,7-di-O-α-l-rhamnopyranoside (4). The resazurin microtiter assay was used to measure the biological activity in vitro against Mycobacterium tuberculosis. The results showed a moderate activity of the methanolic extract with a minimal inhibitory concentration of 128μg/mL. Antioxidant activity was evaluated as free radical scavenging capacity and inhibition of peroxidation. Free radical scavenging capacity was assessed by measuring the scavenging activity of methanolic extract and methanolic fraction on 2,2-diphenyl-1-picrylhydrazyl radical. The methanolic extract showed low values of antioxidant activities, whereas the methanolic fraction exhibited free radical scavenging activity ranging from 20.2% to 91.1%, and the inhibition of peroxidation values ranging from 5.6% to 27.5%. This is the first chemical study reported in the literature about this species.

Predicting football scores via Poisson regression model: applications to the National Football League

Saraiva, Erlandson F.,Suzuki, Adriano K.,Filho, Ciro A.O.,Louzada, Francisco The Korean Statistical Society 2016 Communications for statistical applications and me Vol.23 No.4

Football match predictions are of great interest to fans and sports press. In the last few years it has been the focus of several studies. In this paper, we propose the Poisson regression model in order to football match outcomes. We applied the proposed methodology to two national competitions: the 2012-2013 English Premier League and the 2015 Brazilian Football League. The number of goals scored by each team in a match is assumed to follow Poisson distribution, whose average reflects the strength of the attack, defense and the home team advantage. Inferences about all unknown quantities involved are made using a Bayesian approach. We calculate the probabilities of win, draw and loss for each match using a simulation procedure. Besides, also using simulation, the probability of a team qualifying for continental tournaments, being crowned champion or relegated to the second division is obtained.

A Bayesian cure rate model with dispersion induced by discrete frailty

Cancho, Vicente G.,Zavaleta, Katherine E.C.,Macera, Marcia A.C.,Suzuki, Adriano K.,Louzada, Francisco The Korean Statistical Society 2018 Communications for statistical applications and me Vol.25 No.5

In this paper, we propose extending proportional hazards frailty models to allow a discrete distribution for the frailty variable. Having zero frailty can be interpreted as being immune or cured. Thus, we develop a new survival model induced by discrete frailty with zero-inflated power series distribution, which can account for overdispersion. This proposal also allows for a realistic description of non-risk individuals, since individuals cured due to intrinsic factors (immunes) are modeled by a deterministic fraction of zero-risk while those cured due to an intervention are modeled by a random fraction. We put the proposed model in a Bayesian framework and use a Markov chain Monte Carlo algorithm for the computation of posterior distribution. A simulation study is conducted to assess the proposed model and the computation algorithm. We also discuss model selection based on pseudo-Bayes factors as well as developing case influence diagnostics for the joint posterior distribution through ${\psi}-divergence$ measures. The motivating cutaneous melanoma data is analyzed for illustration purposes.

An extended Lindley distribution

Hassan S. Bakouch,Bander M. Al-Zahrani,Ali A. Al-Shomrani,Vitor A.A. Marchi,Francisco Louzada 한국통계학회 2012 Journal of the Korean Statistical Society Vol.41 No.1

In this paper we introduce an extension of the Lindley distribution which offers a more flexible model for lifetime data. Several statistical properties of the distribution are explored, such as the density, (reversed) failure rate, (reversed) mean residual lifetime,moments, order statistics, Bonferroni and Lorenz curves. Estimation using the maximum likelihood and inference of a random sample from the distribution are investigated. A real data application illustrates the performance of the distribution.

The Marshall-Olkin generalized gamma distribution

Barriga, Gladys D.C.,Cordeiro, Gauss M.,Dey, Dipak K.,Cancho, Vicente G.,Louzada, Francisco,Suzuki, Adriano K. The Korean Statistical Society 2018 Communications for statistical applications and me Vol.25 No.3

Attempts have been made to define new classes of distributions that provide more flexibility for modelling skewed data in practice. In this work we define a new extension of the generalized gamma distribution (Stacy, The Annals of Mathematical Statistics, 33, 1187-1192, 1962) for Marshall-Olkin generalized gamma (MOGG) distribution, based on the generator pioneered by Marshall and Olkin (Biometrika, 84, 641-652, 1997). This new lifetime model is very flexible including twenty one special models. The main advantage of the new family relies on the fact that practitioners will have a quite flexible distribution to fit real data from several fields, such as engineering, hydrology and survival analysis. Further, we also define a MOGG mixture model, a modification of the MOGG distribution for analyzing lifetime data in presence of cure fraction. This proposed model can be seen as a model of competing causes, where the parameter associated with the Marshall-Olkin distribution controls the activation mechanism of the latent risks (Cooner et al., Statistical Methods in Medical Research, 15, 307-324, 2006). The asymptotic properties of the maximum likelihood estimation approach of the parameters of the model are evaluated by means of simulation studies. The proposed distribution is fitted to two real data sets, one arising from measuring the strength of fibers and the other on melanoma data.