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Butts, Carter T. "8. Permutation Models for Relational Data." Sociological Methodology 37, no. 1 (August 2007): 257–81. http://dx.doi.org/10.1111/j.1467-9531.2007.00183.x.
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A common problem in sociology, psychology, biology, geography, and management science is the comparison of dyadic relational structures (i.e., graphs). Where these structures are formed on a common set of elements, a natural question that arises is whether there is a tendency for elements that are strongly connected in one set of structures to be more—or less—strongly connected within another set. We may ask, for instance, whether there is a correspondence between golf games and business deals, trade and warfare, or spatial proximity and genetic similarity. In each case, the data for such comparisons may be continuous or discrete, and multiple relations may be involved simultaneously (e.g., when comparing multiple measures of international trade volume with multiple types of political interactions). We propose here an exponential family of permutation models that is suitable for inferring the direction and strength of association among dyadic relational structures. A linear-time algorithm is shown for MCMC simulation of model draws, as is the use of simulated draws for maximum likelihood estimation (MCMC-MLE) and/or estimation of Monte Carlo standard errors. We also provide an easily performed maximum pseudo-likelihood estimation procedure for the permutation model family, which provides a reasonable means of generating seed models for the MCMC-MLE procedure. Use of the modeling framework is demonstrated via an application involving relationships among managers in a high-tech firm.
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Kulmon, Pavel. "Reversible Jump MCMC for Deghosting in MSPSR Systems." Sensors 21, no. 14 (July 14, 2021): 4815. http://dx.doi.org/10.3390/s21144815.
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This paper deals with bistatic track association and deghosting in the classical frequency modulation (FM)-based multi-static primary surveillance radar (MSPSR). The main contribution of this paper is a novel algorithm for bistatic track association and deghosting. The proposed algorithm is based on a hierarchical model which uses the Indian buffet process (IBP) as the prior probability distribution for the association matrix. The inference of the association matrix is then performed using the classical reversible jump Markov chain Monte Carlo (RJMCMC) algorithm with the usage of a custom set of the moves proposed by the sampler. A detailed description of the moves together with the underlying theory and the whole model is provided. Using the simulated data, the algorithm is compared with the two alternative ones and the results show the significantly better performance of the proposed algorithm in such a simulated setup. The simulated data are also used for the analysis of the properties of Markov chains produced by the sampler, such as the convergence or the posterior distribution. At the end of the paper, further research on the proposed method is outlined.
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Ruffieux, Helene, Anthony C. Davison, Jorg Hager, and Irina Irincheeva. "Efficient inference for genetic association studies with multiple outcomes." Biostatistics 18, no. 4 (March 16, 2017): 618–36. http://dx.doi.org/10.1093/biostatistics/kxx007.
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SUMMARY Combined inference for heterogeneous high-dimensional data is critical in modern biology, where clinical and various kinds of molecular data may be available from a single study. Classical genetic association studies regress a single clinical outcome on many genetic variants one by one, but there is an increasing demand for joint analysis of many molecular outcomes and genetic variants in order to unravel functional interactions. Unfortunately, most existing approaches to joint modeling are either too simplistic to be powerful or are impracticable for computational reasons. Inspired by Richardson and others (2010, Bayesian Statistics 9), we consider a sparse multivariate regression model that allows simultaneous selection of predictors and associated responses. As Markov chain Monte Carlo (MCMC) inference on such models can be prohibitively slow when the number of genetic variants exceeds a few thousand, we propose a variational inference approach which produces posterior information very close to that of MCMC inference, at a much reduced computational cost. Extensive numerical experiments show that our approach outperforms popular variable selection methods and tailored Bayesian procedures, dealing within hours with problems involving hundreds of thousands of genetic variants and tens to hundreds of clinical or molecular outcomes.
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Ayres, Karen L., and David J. Balding. "Measuring Gametic Disequilibrium From Multilocus Data." Genetics 157, no. 1 (January 1, 2001): 413–23. http://dx.doi.org/10.1093/genetics/157.1.413.
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Abstract We describe a Bayesian approach to analyzing multilocus genotype or haplotype data to assess departures from gametic (linkage) equilibrium. Our approach employs a Markov chain Monte Carlo (MCMC) algorithm to approximate the posterior probability distributions of disequilibrium parameters. The distributions are computed exactly in some simple settings. Among other advantages, posterior distributions can be presented visually, which allows the uncertainties in parameter estimates to be readily assessed. In addition, background knowledge can be incorporated, where available, to improve the precision of inferences. The method is illustrated by application to previously published datasets; implications for multilocus forensic match probabilities and for simple association-based gene mapping are also discussed.
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Shalfawi, Shaher A. I. "Bayesian Estimation of Correlation between Measures of Blood Pressure Indices, Aerobic Capacity and Resting Heart Rate Variability Using Markov Chain Monte Carlo Simulation and 95% High Density Interval in Female School Teachers." International Journal of Environmental Research and Public Health 17, no. 18 (September 16, 2020): 6750. http://dx.doi.org/10.3390/ijerph17186750.
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Background: Several explanations regarding the disparity observed in the literature with regard to heart rate variability (HRV) and its association with performance parameters have been proposed: the time of day when the recording was conducted, the condition (i.e., rest, active, post activity) and the mathematical and physiological relationships that could have influenced the results. A notable observation about early studies is that they all followed the frequentist approach to data analyses. Therefore, in an attempt to explain the disparity observed in the literature, the primary purpose of this study was to estimate the association between measures of HRV indices, aerobic performance parameters and blood pressure indices using the Bayesian estimation of correlation on simulated data using Markov Chain Monte Carlo (MCMC) and the equal probability of the 95% high density interval (95% HDI). Methods: The within-subjects with a one-group pretest experimental design was chosen to investigate the relationship between baseline measures of HRV (rest; independent variable), myocardial work (rate–pressure product (RPP)), mean arterial pressure (MAP) and aerobic performance parameters. The study participants were eight local female schoolteachers aged 54.1 ± 6.5 years (mean ± SD), with a body mass of 70.6 ± 11.5 kg and a height of 164.5 ± 6.5 cm. Their HRV data were analyzed in R package, and the Bayesian estimation of correlation was calculated employing the Bayesian hierarchical model that uses MCMC simulation integrated in the JAGS package. Results: The Bayesian estimation of correlation using MCMC simulation reproduced and supported the findings reported regarding norms and the within-HRV-indices associations. The results of the Bayesian estimation showed a possible association (regardless of the strength) between pNN50% and MAP (rho = 0.671; 95% HDI = 0.928–0.004), MeanRR (ms) and RPP (rho = −0.68; 95% HDI = −0.064–−0.935), SDNN (ms) and RPP (rho = 0.672; 95% HDI = 0.918–0.001), LF (ms2) and RPP (rho = 0.733; 95% HDI = 0.935–0.118) and SD2 and RPP (rho = 0.692; 95% HDI = 0.939–0.055). Conclusions: The Bayesian estimation of correlation with 95% HDI on MCMC simulated data is a new technique for data analysis in sport science and seems to provide a more robust approach to allocating credibility through a meaningful mathematical model. However, the 95% HDI found in this study, accompanied by the theoretical explanations regarding the dynamics between the parasympathetic nervous system and the sympathetic nervous system in relation to different recording conditions (supine, reactivation, rest), recording systems, time of day (morning, evening, sleep etc.) and age of participants, suggests that the association between measures of HRV indices and aerobic performance parameters has yet to be explicated.
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Khan, Z., T. Balch, and F. Dellaert. "MCMC Data Association and Sparse Factorization Updating for Real Time Multitarget Tracking with Merged and Multiple Measurements." IEEE Transactions on Pattern Analysis and Machine Intelligence 28, no. 12 (December 2006): 1960–72. http://dx.doi.org/10.1109/tpami.2006.247.
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Kokkala, Juho, and Simo Särkkä. "Combining particle MCMC with Rao-Blackwellized Monte Carlo data association for parameter estimation in multiple target tracking." Digital Signal Processing 47 (December 2015): 84–95. http://dx.doi.org/10.1016/j.dsp.2015.04.004.
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Thi Thu Pham, Huong, Hoa Pham, and Darfiana Nur. "A Bayesian inference for the penalized spline joint models of longitudinal and time-to-event data: A prior sensitivity analysis." Monte Carlo Methods and Applications 26, no. 1 (March 1, 2020): 49–68. http://dx.doi.org/10.1515/mcma-2020-2058.
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AbstractBayesian approaches have been used in the literature to estimate the parameters for joint models of longitudinal and time-to-event data. The main aim of this paper is to analyze the impact of prior distributions on estimating parameters in a proposed fully Bayesian analysis setting for the penalized spline joint models. To achieve this aim, the joint posterior distribution of parameters in survival and longitudinal submodels is presented. The Markov chain Monte Carlo (MCMC) algorithm is then proposed, which consists of the Gibbs sampler (GS) and Metropolis Hastings (MH) algorithms to sample for the target conditional posterior distributions. The prior sensitivity analysis for the baseline hazard rate and association parameters is performed through simulation studies and a case study.
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Gokul, T., and M. R. Srinivasan. "Joint Modeling for Longitudinal Data with Missing Values: A Bayesian Perspective on Human Intelligence." Journal of Scientific Research 13, no. 2 (May 1, 2021): 521–36. http://dx.doi.org/10.3329/jsr.v13i2.50479.
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Joint modeling in longitudinal data is an interesting area of research since it predicts the outcome with covariates that are measured repeatedly over the time. However, there is no proper methodology available in literature to incorporate the joint modeling approach for count-count response data. In addition, there are several situations where longitudinal data might not be possible to collect the complete data and the Missingness may occur due to the absence of the subjects at the follow-up. In this paper, joint modelling for longitudinal count data is adopted using Bayesian Generalized Linear Mixed Model framework to understand the association between the variables. Further, an imputation method is used to handle the missing entries in the data and the efficiency of the methodology has been studied using Markov Chain Monte-Carlo (MCMC) technique. An application to the proposed methodology has been discussed and identified the suitable nutritional supplements in Bayesian perspective without eliminating the missing entries in the dataset.
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Pham, Thi Mui, and Maria Kateri. "Inference for Ordinal Log-Linear Models Based on Algebraic Statistics." Journal of Algebraic Statistics 10, no. 1 (April 10, 2019): 30–50. http://dx.doi.org/10.18409/jas.v10i1.74.
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Tools of algebraic statistics combined with MCMC algorithms have been used in contingency table analysis for model selection and model fit testing of log-linear models. However, this approach has not been considered so far for association models, which are special log-linear models for tables with ordinal classification variables. The simplest association model for two-way tables, the uniform (U) association model, has just one parameter more than the independence model and is applicable when both classification variables are ordinal. Less parsimonious are the row (R) and column (C) effect association models, appropriate when at least one of the classification variables is ordinal. Association models have been extended for multidimensional contingency tables as well. Here, we adjust algebraic methods for association models analysis and investigate their eligibility, focusing mainly on two-way tables. They are implemented in the statistical software R and illustrated on real data tables. Finally the algebraic model fit and selection procedure is assessed and compared to the asymptotic approach in terms of a simulation study.
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Achcar, Jorge Alberto, Edson Zangiacomi Martinez, Aparecida Doniseti Pires de Souza, Vilma Mayumi Tachibana, and Edilson Ferreira Flores. "Use of Poisson spatiotemporal regression models for the Brazilian Amazon Forest: malaria count data." Revista da Sociedade Brasileira de Medicina Tropical 44, no. 6 (December 2011): 749–54. http://dx.doi.org/10.1590/s0037-86822011000600019.
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INTRODUCTION: Malaria is a serious problem in the Brazilian Amazon region, and the detection of possible risk factors could be of great interest for public health authorities. The objective of this article was to investigate the association between environmental variables and the yearly registers of malaria in the Amazon region using Bayesian spatiotemporal methods. METHODS: We used Poisson spatiotemporal regression models to analyze the Brazilian Amazon forest malaria count for the period from 1999 to 2008. In this study, we included some covariates that could be important in the yearly prediction of malaria, such as deforestation rate. We obtained the inferences using a Bayesian approach and Markov Chain Monte Carlo (MCMC) methods to simulate samples for the joint posterior distribution of interest. The discrimination of different models was also discussed. RESULTS: The model proposed here suggests that deforestation rate, the number of inhabitants per km², and the human development index (HDI) are important in the prediction of malaria cases. CONCLUSIONS: It is possible to conclude that human development, population growth, deforestation, and their associated ecological alterations are conducive to increasing malaria risk. We conclude that the use of Poisson regression models that capture the spatial and temporal effects under the Bayesian paradigm is a good strategy for modeling malaria counts.
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Gregorius, Hans-Rolf. "Model-based analysis of latent factors." Web Ecology 18, no. 2 (November 14, 2018): 153–62. http://dx.doi.org/10.5194/we-18-153-2018.
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Abstract. The detection of community or population structure through analysis of explicit cause–effect modeling of given observations has received considerable attention. The complexity of the task is mirrored by the large number of existing approaches and methods, the applicability of which heavily depends on the design of efficient algorithms of data analysis. It is occasionally even difficult to disentangle concepts and algorithms. To add more clarity to this situation, the present paper focuses on elaborating the system analytic framework that probably encompasses most of the common concepts and approaches by classifying them as model-based analyses of latent factors. Problems concerning the efficiency of algorithms are not of primary concern here. In essence, the framework suggests an input–output model system in which the inputs are provided as latent model parameters and the output is specified by the observations. There are two types of model involved, one of which organizes the inputs by assigning combinations of potentially interacting factor levels to each observed object, while the other specifies the mechanisms by which these combinations are processed to yield the observations. It is demonstrated briefly how some of the most popular methods (Structure, BAPS, Geneland) fit into the framework and how they differ conceptually from each other. Attention is drawn to the need to formulate and assess qualification criteria by which the validity of the model can be judged. One probably indispensable criterion concerns the cause–effect character of the model-based approach and suggests that measures of association between assignments of factor levels and observations be considered together with maximization of their likelihoods (or posterior probabilities). In particular the likelihood criterion is difficult to realize with commonly used estimates based on Markov chain Monte Carlo (MCMC) algorithms. Generally applicable MCMC-based alternatives that allow for approximate employment of the primary qualification criterion and the implied model validation including further descriptors of model characteristics are suggested.
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O'Reilly, K. M., J. C. Low, M. J. Denwood, D. L. Gally, J. Evans, G. J. Gunn, D. J. Mellor, S. W. J. Reid, and L. Matthews. "Associations between the Presence of Virulence Determinants and the Epidemiology and Ecology of Zoonotic Escherichia coli." Applied and Environmental Microbiology 76, no. 24 (October 15, 2010): 8110–16. http://dx.doi.org/10.1128/aem.01343-10.
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ABSTRACT The severity of human infection with pathogenic Escherichia coli depends on two major virulence determinants (eae and stx) that, respectively, produce intimin and Shiga toxin. In cattle, both may enhance colonization, but whether this increases fitness by enhancing cattle-to-cattle transmission in the field is unknown. In E. coli O157, the almost uniform presence of the virulence determinants in cattle isolates prevents comparative analysis. The availability to this study of extensive non-O157 E. coli data, with much greater diversity in carriage of virulence determinants, provides the opportunity to gain insight into their potential impact on transmission. Dynamic models were used to simulate expected prevalence distributions for serogroups O26 and O103. Transmission parameters were estimated by fitting model outputs to prevalence data from Scottish cattle using a Bayesian Markov chain Monte Carlo (MCMC) approach. Despite similar prevalence distributions for O26 and O103, their transmission dynamics were distinct. Serogroup O26 strains appear well adapted to the cattle host. The dynamics are characterized by a basic reproduction ratio (R 0) of >1 (allowing sustained cattle-to-cattle transmission), a relatively low transmission rate from environmental reservoirs, and substantial association with eae on transmission. The presence of stx 2 was associated with reduced transmission. In contrast, serogroup O103 appears better adapted to the noncattle environment, characterized by an R 0 value of <1 for plausible test sensitivities, a significantly higher transmission rate from noncattle sources than serogroup O26, and an absence of fitness benefits associated with the carriage of eae. Thus, the association of eae with enhanced transmission depends on the E. coli serogroup. Our results suggest that the capacity of E. coli strains to derive fitness benefits from virulence determinants influences the prevalence in the cattle population and the ecology and epidemiology of the host organism.
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Bruck, Irina, and Daniel L. Kaplan. "Conserved mechanism for coordinating replication fork helicase assembly with phosphorylation of the helicase." Proceedings of the National Academy of Sciences 112, no. 36 (August 24, 2015): 11223–28. http://dx.doi.org/10.1073/pnas.1509608112.
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Dbf4-dependent kinase (DDK) phosphorylates minichromosome maintenance 2 (Mcm2) during S phase in yeast, and Sld3 recruits cell division cycle 45 (Cdc45) to minichromosome maintenance 2-7 (Mcm2-7). We show here DDK-phosphoryled Mcm2 preferentially interacts with Cdc45 in vivo, and that Sld3 stimulates DDK phosphorylation of Mcm2 by 11-fold. We identified a mutation of the replication initiation factor Sld3, Sld3-m16, that is specifically defective in stimulating DDK phosphorylation of Mcm2. Wild-type expression levels of sld3-m16 result in severe growth and DNA replication defects. Cells expressing sld3-m16 exhibit no detectable Mcm2 phosphorylation in vivo, reduced replication protein A-ChIP signal at an origin, and diminished Go, Ichi, Ni, and San association with Mcm2-7. Treslin, the human homolog of Sld3, stimulates human DDK phosphorylation of human Mcm2 by 15-fold. DDK phosphorylation of human Mcm2 decreases the affinity of Mcm5 for Mcm2, suggesting a potential mechanism for helicase ring opening. These data suggest a conserved mechanism for replication initiation: Sld3/Treslin coordinates Cdc45 recruitment to Mcm2-7 with DDK phosphorylation of Mcm2 during S phase.
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Worku, Zeleke. "The impact of service quality on the viability of start-up businesses." Corporate Ownership and Control 13, no. 3 (2016): 518–22. http://dx.doi.org/10.22495/cocv13i3c3p10.
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A 3-year long survey was conducted in the Tshwane geographical region of Gauteng Province in South Africa in order to identify and quantify key predictors of adequate municipal services that are routinely provided to customers who operate newly established small businesses in the City of Tshwane, Pretoria, South Africa. Data was collected by using a structured, pre-tested and validated questionnaire of study from a stratified random sample of size 1, 058 small businesses. The key objective of study was to assess the relationship between viability in small businesses and the provision of quality municipal services by the City of Tshwane. The study was conducted against the background of a high failure rate among newly established small businesses in the City of Tshwane. The study was conducted over a 3-year period (2012 to 2014). Data was collected monthly during the three-year period of study on socioeconomic variables that are known to affect the perception of business operators on the quality of municipal services to business operators and the general public. Statistical procedures such as cross-tab analyses, panel data analysis, Markov Chain Monte Carlo (MCMC) algorithms and Bayesian methods were used for estimating parameters. The study showed that there was a significant association between positive perception of business operators on the quality of municipal services provided to them and viability of businesses. The results showed that 87% of viable businesses were satisfied with the quality of routine municipal services that were provided to them by the City of Tshwane. The corresponding figure for non-viable businesses was only 14%. The viability of businesses was significantly influenced by 3 predictor variables. These predictor variables were: lack of capacity for fulfilling the business and entrepreneurial needs of newly established businesses [Hazard Ratio = 3.58; P=0.000; 95% C. I. = (1.45, 5.46)], inappropriate policy [Hazard Ratio = 3.19; P=0.000; 95% C. I. = (1.39, 5.28)], and lack of tailor made training programmes directed at newly established small businesses [Hazard Ratio = 2.89; P=0.000; 95% C. I. = (1.24, 4.77)], in a decreasing order of strength. Similar findings were obtained from the analyses of in-depth interviews.
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Sterner, Jacqueline M., Susan Dew-Knight, Christine Musahl, Sally Kornbluth, and Jonathan M. Horowitz. "Negative Regulation of DNA Replication by the Retinoblastoma Protein Is Mediated by Its Association with MCM7." Molecular and Cellular Biology 18, no. 5 (May 1, 1998): 2748–57. http://dx.doi.org/10.1128/mcb.18.5.2748.
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ABSTRACT A yeast two-hybrid screen was employed to identify human proteins that specifically bind the amino-terminal 400 amino acids of the retinoblastoma (Rb) protein. Two independent cDNAs resulting from this screen were found to encode the carboxy-terminal 137 amino acids of MCM7, a member of a family of proteins that comprise replication licensing factor. Full-length Rb and MCM7 form protein complexes in vitro, and the amino termini of two Rb-related proteins, p107 and p130, also bind MCM7. Protein complexes between Rb and MCM7 were also detected in anti-Rb immunoprecipitates prepared from human cells. The amino-termini of Rb and p130 strongly inhibited DNA replication in an MCM7-dependent fashion in a Xenopus in vitro DNA replication assay system. These data provide the first evidence that Rb and Rb-related proteins can directly regulate DNA replication and that components of licensing factor are targets of the products of tumor suppressor genes.
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Najadat, Hassan, Izzat Alsmadi, and Yazan Shboul. "Predicting Software Projects Cost Estimation Based on Mining Historical Data." ISRN Software Engineering 2012 (April 10, 2012): 1–8. http://dx.doi.org/10.5402/2012/823437.
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In this research, a hybrid cost estimation model is proposed to produce a realistic prediction model that takes into consideration software project, product, process, and environmental elements. A cost estimation dataset is built from a large number of open source projects. Those projects are divided into three domains: communication, finance, and game projects. Several data mining techniques are used to classify software projects in terms of their development complexity. Data mining techniques are also used to study association between different software attributes and their relation to cost estimation. Results showed that finance metrics are usually the most complex in terms of code size and some other complexity metrics. Results showed also that games applications have higher values of the SLOCmath, coupling, cyclomatic complexity, and MCDC metrics. Information gain is used in order to evaluate the ability of object-oriented metrics to predict software complexity. MCDC metric is shown to be the first metric in deciding a software project complexity. A software project effort equation is created based on clustering and based on all software projects’ attributes. According to the software metrics weights values developed in this project, we can notice that MCDC, LOC, and cyclomatic complexity of the traditional metrics are still the dominant metrics that affect our classification process, while number of children and depth of inheritance are the dominant from the object-oriented metrics as a second level.
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Koszinowski, U. H., G. M. Keil, H. Schwarz, J. Schickedanz, and M. J. Reddehase. "A nonstructural polypeptide encoded by immediate-early transcription unit 1 of murine cytomegalovirus is recognized by cytolytic T lymphocytes." Journal of Experimental Medicine 166, no. 1 (July 1, 1987): 289–94. http://dx.doi.org/10.1084/jem.166.1.289.
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We have constructed target cells by cotransfection of the MHC gene Ld and fragments of murine cytomegalovirus (MCMV) DNA coding for nonstructural immediate-early (IE) proteins. Transfectants were tested by using CTL clone IE1 with specificity for an IE epitope presented in association with Ld. Data show that clone IE1 recognizes a product of the ie1 transcription unit of MCMV, and that its specificity is shared by approximately 25% of polyclonal IE-specific CTL. The results provide the first definite evidence that expression of a herpes virus IE gene encoding a regulatory protein gives rise to antigen expression detectable by specific CTL.
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Nosike, R. J., O. F. Nwakpu, C. N. Okocha, E. C. Inyang, J. C. Ezike, and D. N. Onunkwo. "Phenotypic correlations between biologic markers and growth traits in Arbor acres broiler chicken strain." Nigerian Journal of Animal Production 45, no. 2 (December 25, 2020): 21–28. http://dx.doi.org/10.51791/njap.v45i2.481.
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The study was conducted to determine the correlations between biologic markers,haematological indices and growth traits in Arbor Acres broiler strain. A total of 120 Arbor acres strain were used for the experiment which lasted for 56 days. The birds were raised in separate deep litter pens. Data collected include biologic markers: hemoglobin (Hb), packed cell volume (PCV), white blood cell (WBC), red blood cell (RBC), mean cell volume (MCV), mean cellular hemoglobin (MCH), mean cellular hemoglobin concentration (MCHC) and biochemical parameters include: blood glucose (GLU) and total serum protein(PRT). Growth traits include: body weight (BW), body length (BL), shank length (SL), keel length (KL), wing length (WL), breast width (BWD) and drumstick length (DSL). The result obtained showed that MCHC in week 4 it associated significantly with breast length(rp=0.989) and keel length (rp= -0.986), whereas in week 6, serum protein, MCH, PCV, WBC and RBC proved significant markers based on their significant association (P<0.05;P<0.01) with SL (rp=0.975), KL (rp=0.981), DSL (rp= -0.982; -0.989) and BL (rp= -0.991). In week 8, Hb, WBC, MCV, MCH and MCHC proved to be useful markers for selecting keel length, breast length, body length, body length and thigh width in Arbor Acre. Highest correlation was observed between WBC and BL (rp= -0.991) and between MCH and breast length (rp= 0.991) in the 6 week. Due to the limited associations observed in week 4, it may be more reliable to apply the biologic markers in selection programs, starting at the 6 week for Arbor Acres broiler strains. This study advocates that highly polymorphic DNA-based markers which are more reliable should be attempted for improving body weight of broilers.
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Abro, Saleem Ullah, Quratulain Saleem, Amna Begum, Sarah Azhar, Amber Naseer, and Aijaz Ahmed Qureshi. "Association of BMI (Body Mass Index) to hemoglobin and red blood cell indices among adolescents." Professional Medical Journal 27, no. 10 (October 10, 2020): 2210–15. http://dx.doi.org/10.29309/tpmj/2020.27.10.4470.
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Objectives: Hemoglobin & red blood cell indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width) among adolescent. Study Design: Cross-Sectional study (Descriptive). Setting: Department of Physiology, Baqai Medical University (BMU) Karachi. Period: 6 months from February to August 2017. Material & Methods: A total of 500 students of MBBS, BDS, DPT with having age ranges from 18-25 years were enrolled in this study. The anthropometric measurement [height (m2) and weight (kg)] was recorded for calculation of the Body Mass Index and Complete blood count i-e Hemoglobin (Hb%), Mean Corpuscular Volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), Red cell distribution width (RDW) was done and calculated. Data analysis was done on Microsoft excel & SPSS version 22.0 was used. Results: It was seen that the comparison of Hb%, MCV & RDW had no significant (p>0.001) association of study participants to different categories of Body Mass Index. Mean corpuscular hemoglobin (MCH) (X²=28.278, p<0.001) and Mean corpuscular hemoglobin concentration (MCHC) (X²=15.659, p=0.016) were statistically significantly association with different categories of Body Mass Index. Conclusion: Mean corpuscular hemoglobin and Mean corpuscular hemoglobin concentration had statistically significant (p<0.001) association with body mass index (BMI).
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Ashad Alam, Md, Osamu Komori, Hong-Wen Deng, Vince D. Calhoun, and Yu-Ping Wang. "Robust kernel canonical correlation analysis to detect gene-gene co-associations: A case study in genetics." Journal of Bioinformatics and Computational Biology 17, no. 04 (August 2019): 1950028. http://dx.doi.org/10.1142/s0219720019500288.
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The kernel canonical correlation analysis based U-statistic (KCCU) is being used to detect nonlinear gene–gene co-associations. Estimating the variance of the KCCU is however computationally intensive. In addition, the kernel canonical correlation analysis (kernel CCA) is not robust to contaminated data. Using a robust kernel mean element and a robust kernel (cross)-covariance operator potentially enables the use of a robust kernel CCA, which is studied in this paper. We first propose an influence function-based estimator for the variance of the KCCU. We then present a non-parametric robust KCCU, which is designed for dealing with contaminated data. The robust KCCU is less sensitive to noise than KCCU. We investigate the proposed method using both synthesized and real data from the Mind Clinical Imaging Consortium (MCIC). We show through simulation studies that the power of the proposed methods is a monotonically increasing function of sample size, and the robust test statistics bring incremental gains in power. To demonstrate the advantage of the robust kernel CCA, we study MCIC data among 22,442 candidate Schizophrenia genes for gene–gene co-associations. We select 768 genes with strong evidence for shedding light on gene–gene interaction networks for Schizophrenia. By performing gene ontology enrichment analysis, pathway analysis, gene–gene network and other studies, the proposed robust methods can find undiscovered genes in addition to significant gene pairs, and demonstrate superior performance over several of current approaches.
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Kohsari, Maryam, Mehdi Moradinazar, Zohreh Rahimi, Farid Najafi, Yahya Pasdar, Atefeh Moradi, and Ebrahim Shakiba. "Association between RBC Indices, Anemia, and Obesity-Related Diseases Affected by Body Mass Index in Iranian Kurdish Population: Results from a Cohort Study in Western Iran." International Journal of Endocrinology 2021 (September 4, 2021): 1–13. http://dx.doi.org/10.1155/2021/9965728.
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Objective. The relationship between RBC indices and metabolic diseases remains unclear. The association between anemia and obesity is also controversial. The present study aimed to investigate the relationship between RBC indices and metabolic diseases caused by obesity and evaluate the effect of body mass index (BMI) on RBC indices on the Ravansar cohort data. Method. For the purpose of this study, 9826 participants aged 35–65 years (5158 females and 4668 males) were recruited in the analyses. A quadratic prediction fit plot investigated the association between RBC indices with BMI and lipid profile. The odds ratio of obesity-related diseases in each quartile category of RBC indices and anemia was estimated using multivariable logistic regression models. Results. Subjects in the fourth quartiles of RBC count, hematocrit (HCT), hemoglobin (HGB), and red cell distribution width (RDW) had a higher risk for obesity-related diseases compared to the first quartiles. However, individuals with the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in fourth quartiles had lower ORs of obesity-related diseases. While BMI reduced the effect of RBC count, HCT, HGB, and RDW on the incidence risk of obesity-related disease, it increased the impact of MCV, MCH, and MCHC. There was a negative association between BMI and RBC indices except for RDW. The BMI effect on RBC indices was different in normal and obese individuals. BMI in mild anemia lowered the risk of metabolic diseases, but it increased the risk of metabolic diseases for moderate anemia. Conclusion. A higher risk of obesity-related diseases was observed in the fourth quartiles of RBC count, HCT, HGB, and RDW compared to the first quartiles. However, the incidence risk was lower for MCV, MCH, and MCHC. BMI plays an anemia-type dependent role in the relationship. Consideration should be given to the type of anemia in the relationship between BMI and anemia.
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Farris, Nicholas, Henny H. Billett, Craig A. Branch, Caterina Minniti, Kelsey Branch, and Seetharama A. Acharya. "The Association of White Matter Hyperintensity Volume and Sickle Cell Anemia." Blood 128, no. 22 (December 2, 2016): 1321. http://dx.doi.org/10.1182/blood.v128.22.1321.1321.
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Abstract Background:While overt cerebrovascular accidents (CVAs) are well recognized in patients with Sickle Cell Anemia (SCA), more subtle cerebrovascular diseases, including neurocognitive performance deficits and silent cerebral infarcts (SCIs), are present but less well understood, particularly in adults. SCI manifests as asymptomatic white matter hyperintensities (WMH) found on T2-weighted, diffusion-weighted or Fluid Attenuated Inversion Recovery (FLAIR) magnetic resonance images. WMH volume has been found to be negatively associated with IQ in SCA. We sought to clarify the role of WMH load by MRI using region of interest volume calculations in patients particularly at risk, adult patients with SCA. Methods: SCA (HbSS/HbSβ0) and AA subjects, ages 18-55 years old, with no evidence of TIA/Stroke, prothrombotic history, clotting or bleeding disorder, and not on anticoagulation were recruited. Hydroxyurea use was noted but was neither an inclusion nor exclusion criterion. Evaluation included a routine questionnaire for basic social, educational and health information. Steady state laboratory evaluation was obtained within one week of imaging. Neurocognitive performance was evaluated by the Cogstate battery at the time of the MRI. Cogstate analysis included tests of executive function (the Groton Maze Learning Test or GMLT), recall, social and emotional cognition and learning. 3T MRI included 3D-T1w , T2, FLAIR, pseudo-continuous arterial spin labeling and diffusion tensor imaging (DTI). Fractional anisotropy (FA) and mean diffusivity (MD) were extracted from DTI data and calculated for gray matter (GM) and white matter (WM). Cerebral blood flow (CBF) was also calculated for GM and WM separately. FLAIR images were reviewed (reviewer was blind for group) for WMHs using the NIH image analysis package MIPAV (http://mipav.cit.nih.gov/). WMH signal regions (ROI) were identified and selected/masked using the 'levelSet' ROI function on a slice-by-slice basis. ROIs were grouped, and average WMH volume (using slice thickness) calculated for each subject using the MIPAV Statistics Generator. Results:15 SCA and 11 AA subjects were recruited for the tailored questionnaire, 3T MRI, routine laboratory testing and neurocognitive testing. Both number and volume of ROI were increased in SCA patients (p=0.018 and p=0.052 respectively). GM and WM CBF were markedly increased in SCA patients (p=0.005 for both). GM-MD was increased in SCA patients (p=0.046) while increases in WM-FA and MD were of borderline significance (p=0.055 and p=0.564) respectively. These data are shown in the Table below. Although SCA patients fared significantly worse on the GMLT, p=0.020, there was no association of the GMLT with ROI volume (p=0.96). ROI volume was positively associated with MCHC (p=0.035), a dense cell biomarker, but we could not find an association with Hb, indirect bilirubin or reticulocyte count. MDWM FA and GM-MD also correlated significantly with MCHC but the major associations of DTI measurements, like those of both grey matter (GM) and white matter (WM) cerebral blood flow, were correlated with Hb levels (both GM and WM MD, p=0.004). There was no association of oxygen saturation or change in oxygen saturation with ROI number of volume. Conclusions: The etiology of the documented cognitive difference between SCA and HbA is unclear. Although there is some suggestion that WMH correlates with SCA outcome and may explain this discrepancy, the association is weak. We could not find as association of ROI number or ROI volume with cognitive outcome, nor could we find an association of ROI volume with any pertinent laboratory parameters except MCHC. Unlike CBF, WMH volume load, as represented by ROI volume, does not appear to correlate with the degree of anemia or with clinical disease. Whether cognitive impairment requires a "second hit" or whether it is multifactorial in nature, stemming from chronic oxidative stress, intermittent hypoxia or other factors, remains to be determined. Table Table. Disclosures No relevant conflicts of interest to declare.
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Abro, Saleemullah, Qurratulain Saleem, Syeda Asiya Parveen, Ali Ahmed, Syed Hafeezul Hussan, and Taif Hameed. "Association of body mass index with hemoglobin level, erythrocyte indices and red cell distribution width." Professional Medical Journal 28, no. 03 (March 10, 2021): 311–17. http://dx.doi.org/10.29309/tpmj/2021.28.03.5334.
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Objectives: Objective of this study is to evaluate the association of body mass index with hemoglobin Level, erythrocyte Indices and red cell distribution width in medical students of Baqai Medical University Karachi. Study Design: Descriptive cross - sectional study. Setting: Physiology Department of Baqai Medical University Karachi. Period: 15 February 2017 to 15 August 2017. Material & Methods: A total of 500 students were enrolled in this study. The anthropometric measurement [height (m2) and weight (kg)] was recorded for calculation of the Body Mass Index and Complete blood count i-e Hemoglobin%, erythrocyte indices {Mean corpuscular volume(MCV), Mean corpuscular hemoglobin(MCH), Mean corpuscular hemoglobin concentration (MCHC), Red cell distribution width (RDW) were done and Mentzer’s Index was calculated. Statistical Package for the Social Sciences (SPSS) version 22.0 was used to analyze the collected data. Results: It was observed in 500 medical students that 36% of the students were having low hemoglobin % level, while low values of erythrocyte indices (MCH: 38.0%, MCV 36.6% and MCHC 39.0% respectively) and 93.8% of participants had a higher values of RDW in study participants. Iron deficiency anemia (87.2%) and thalassemia (carrier or minor: 12.8%) were determined by using Menterzer Index. Mean body mass index of study participants were 23.04±3.68 and it was observed in study participants that only RDW was significantly associated with obese students (X²=9.878, p=0.02). Conclusion: With regard to our study results, higher percentage (87.2%) of Iron deficiency anemia were observed and having association between red cell distribution width to obesity.
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Xu, Maonian, Hugo De Boer, Elin Soffia Olafsdottir, Sesselja Omarsdottir, and Starri Heidmarsson. "Phylogenetic diversity of the lichenized algal genus Trebouxia (Trebouxiophyceae, Chlorophyta): a new lineage and novel insights from fungal-algal association patterns of Icelandic cetrarioid lichens (Parmeliaceae, Ascomycota)." Botanical Journal of the Linnean Society 194, no. 4 (July 20, 2020): 460–68. http://dx.doi.org/10.1093/botlinnean/boaa050.
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Abstract Lichens have high tolerance to harsh environmental conditions, where lichen symbiont interactions (e.g. myco- and photobionts) may play a crucial role. The characterization of fungal-algal association patterns is essential to understand their symbiotic interactions. This study investigated fungal-algal association patterns in Icelandic cetrarioid lichens using a multi-locus phylogenetic framework, including fungal nrITS, MCM7, mtSSU, RPB1 and RPB2 and algal nrITS, nrLSU, rbcL and mtCOXII data. Most Icelandic cetrarioid lichenized fungi were found to be specifically associated to the known Trebouxia clade “S” (Trebouxia simplex/suecica group), whereas the lichen-forming fungus Cetrariella delisei forms a symbiosis with a previously unrecognized lineage of Trebouxia, provisionally named as the “D” clade. This new Trebouxia lineage is supported by maximum likelihood and Bayesian phylogenetic analyses using all four included algal loci.
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Huang, L., W. Zhang, and S. Y. Roth. "Amino termini of histones H3 and H4 are required for a1-alpha2 repression in yeast." Molecular and Cellular Biology 17, no. 11 (November 1997): 6555–62. http://dx.doi.org/10.1128/mcb.17.11.6555.
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The Saccharomyces cerevisiae alpha2 repressor controls two classes of cell-type-specific genes in yeast through association with different partners. alpha2-Mcm1 complexes repress a cell-specific gene expression in haploid alpha cells and diploid a/alpha cells, while a1-alpha2 complexes repress haploid-specific genes in diploid cells. In both cases, repression is mediated through Ssn6-Tu1 corepressor complexes that are recruited via direct interactions with alpha2. We have previously shown that nucleosomes are positioned adjacent to the alpha2-Mcm1 operator under conditions of repression and that Tupl interacts directly with histones H3 and H4. Here, we examine the role of chromatin in a1-alpha2 repression to determine if chromatin is a general feature of repression by Ssn6-Tup1. We find that mutations in the amino terminus of histone H4 cause a 4- to 11-fold derepression of a reporter gene under a1-alpha2 control, while truncation of the H3 amino terminus has a more modest (3-fold or less) effect. Strikingly, combination of the H3 truncation with an H4 mutation causes a 40-fold decrease in repression, clearly indicating a central role for these histones in a1-alpha2-mediated repression. However, in contrast to the ordered positioning of nucleosomes adjacent to the alpha2-Mcm1 operator, nucleosomes are not positioned adjacent to the a1-alpha2 operator in diploid cells. Our data indicate that chromatin is important to Ssn6-Tup1-mediated repression but that the degrees of chromatin organization directed by these proteins differ at different promoters.
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Boldrini, Laura, Pinuccia Faviana, Luca Galli, Federico Paolieri, Paola Anna Erba, and Massimo Bardi. "Multi-Dimensional Scaling Analysis of Key Regulatory Genes in Prostate Cancer Using the TCGA Database." Genes 12, no. 9 (August 29, 2021): 1350. http://dx.doi.org/10.3390/genes12091350.
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Prostate cancer (PC) is a polygenic disease with multiple gene interactions. Therefore, a detailed analysis of its epidemiology and evaluation of risk factors can help to identify more accurate predictors of aggressive disease. We used the transcriptome data from a cohort of 243 patients from the Cancer Genome Atlas (TCGA) database. Key regulatory genes involved in proliferation activity, in the regulation of stress, and in the regulation of inflammation processes of the tumor microenvironment were selected to test a priori multi-dimensional scaling (MDS) models and create a combined score to better predict the patients’ survival and disease-free intervals. Survival was positively correlated with cortisol expression and negatively with Mini-Chromosome Maintenance 7 (MCM7) and Breast-Related Cancer Antigen2 (BRCA2) expression. The disease-free interval was negatively related to the expression of enhancer of zeste homolog 2 (EZH2), MCM7, BRCA2, and programmed cell death 1 ligand 1 (PD-L1). MDS suggested two separate pathways of activation in PC. Within these two dimensions three separate clusters emerged: (1) cortisol and brain-derived neurotrophic factor BDNF, (2) PD-L1 and cytotoxic-T-lymphocyte-associated protein 4 (CTL4); (3) and finally EZH2, MCM7, BRCA2, and c-Myc. We entered the three clusters of association shown in the MDS in several Kaplan–Meier analyses. It was found that only Cluster 3 was significantly related to the interval-disease free, indicating that patients with an overall higher activity of regulatory genes of proliferation and DNA repair had a lower probability to have a longer disease-free time. In conclusion, our data study provided initial evidence that selecting patients with a high grade of proliferation and DNA repair activity could lead to an early identification of an aggressive PC with a potentials for metastatic development.
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Allahabadi, Sachin, Sonali E. Feeley, Drew A. Lansdown, Nirav K. Pandya, and Brian T. Feeley. "Influential Articles on Pediatric and Adolescent Anterior Cruciate Ligament Injuries: A Bibliometric Analysis." Orthopaedic Journal of Sports Medicine 9, no. 6 (June 1, 2021): 232596712110107. http://dx.doi.org/10.1177/23259671211010772.
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Background: The understanding of pediatric anterior cruciate ligament (ACL) injuries and optimal treatment has evolved significantly. Influential articles have been previously evaluated using article citations to determine impact. Purpose: To identify and characterize the 50 most cited and recent influential articles relating to pediatric and adolescent ACL injuries, to examine trends in publication characteristics, and to evaluate correlations of study citations with quality of evidence. Study Design: Cross-sectional study. Methods: The top 50 most cited articles on pediatric and adolescent ACL injuries were gathered using the Web of Science and Scopus online databases by averaging the number of citations from each database. Articles from recent years were also aggregated and sorted by citation density (citations/year). Publication and study characteristics were recorded. Level of evidence and methodologic quality were assessed where applicable using the modified Coleman Methodology Score (mCMS), modified Jadad scale, and Methodological Index for Non-Randomized Studies (MINORS). Spearman correlation was used to evaluate the association between citation data and level of evidence or methodologic quality scorings. Results: The top 50 cited papers had a mean of 117.5 ± 58.8 citations (range, 58.5-288.5 citations), with a mean citation density of 9.4 ± 5.4 citations per year (range, 2.9-25.8 citations/year); 80% were published in 2000 or later, and 6% were considered basic science. Articles were mainly level 4 evidence (27/42; 64.3%), and none was level 1. There were moderate, significant associations between publication year and level of evidence ( r S = −0.45; P = .0030) and citation density and publication year ( r S = 0.59; P < .001). Mean methodologic quality scores were as follows: mCMS, 53 ± 7.2 (range, 39-68); modified Jadad scale, 3.2 ± 1.1 (range, 2-6); and MINORS, 11.2 ± 3.2 (range, 6-20). There was a significant, strong correlation between rank of mean citations and modified Jadad scale ( r S = 0.76; P < .0001), suggesting poorer score associated with more mean citations. Conclusion: Influential articles on pediatric and adolescent ACL injuries were relatively recent, with a low proportion of basic science–type articles. Most of the studies had a lower evidence level and poor methodologic quality scores. Higher methodologic quality did not correlate positively with citation data.
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Hossain, Mohammad S., John D. Roback, and Edmund K. Waller. "MCMV Infection Lowers the Threshold for the Development of Clinical GvHD after Allogeneic Bone Marrow Transplantation." Blood 104, no. 11 (November 16, 2004): 2125. http://dx.doi.org/10.1182/blood.v104.11.2125.2125.
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Abstract CMV infection is reported to increase the incidence and severity of chronic GvHD and clinical data have shown that preemptive antiviral therapy decreased the risk of extensive chronic GvHD. Using mouse model of Allogeneic BMT, we investigated the mechanism for the association of MCMV infection and GvHD. We hypothesize that MCMV infection leads to generalized immune activation and increases the number of donor derived allo-reactive T cells and GvHD activity. Methods: A parenteral to F1 mouse BMT model was used to study anti-CMV immunity and GvHD. Low dose splenocytes (3x106) from MCMV immunized C57BL/6 donors (H-2b, Thy1.2+, CD45.1+) were transplanted with 5x106 T cell depleted bone marrow (TCD BM) from congeneic mice (H-2b, Thy1.1+, CD45.2+) into lethally irradiated (11Gy) CB6F1 recipients (C57BL/6 x Balb/C, H-2b/d, Thy1.2+, CD45.2+). Previous work has established this as a dose that protects against CMV without immediate lethality from GvHD. Non-GvHD control mice received a dose of Amotosalen treated splenocytes (10x106) and 5x106 TCD BM that protects against CMV without GvHD. Recipient mice were infected i.p. with a supralethal dose (2.5x104 pfu) of MCMV 7 days post transplant. Clinical GvHD was monitored twice weekly by weight loss, hair loss, ruffled fur, diarrhea, and decreased activity. T cell chimerism in recipient spleen and thymus, and MCMV peptide specific tetramer+CD8+ T cells were determined by flow cytometry. Liver and lung viral loads were determined by counting PFU in tissue homogenates plated onto 3T3 confluent monolayers. Results: During the acute phase of MCMV infection (day 3 to 14 post infection), recipient mice that received 3x106 untreated donor splenocytes developed GvHD characterized by weight loss and higher mortality than the non-GvHD control mice. Although both GvHD+ and control mice effectively cleared the virus from their liver, delayed viral clearance from the lung was found in non-GvHD recipients. Viral clearance was associated with expansion of donor spleen-derived MCMV peptide specific tetramer+ CD8+ T cells. The kinetics of donor T-cell expansion varied significantly between the two treatment groups, with GvHD+ recipients showed rapid early expansion of donor derived T-cells followed by the development of GvHD with subsequent lymphopenia. Recipients of Amotosalen-treated splenocytes had more gradual expansion of total and 400-fold expansion of antigen specific T-cells with sustained lymphoid reconstitution. GvHD+ recipients of untreated splenocytes had complete chimerism comprised of >80% of CD8+ donor T cells whereas non-GvHD controls had significant expansion of host derived T cells following MCMV infection and lacked allo-reactive of donor- spleen-derived T cells. Thymic function was inhibited among animals that developed GvHD and preserved among control mice throughout the infectious phase. Very delayed CMV infection (on day 60 after transplant) in mice with established chronic GvHD exacerbated GvHD and was associated with delayed lung viral clearance. Conclusion: After CMV infection there is extensive expansion of allo-reactive T cells in GvHD+ mice with associated damage to the microenvironment in the spleen and thymus. Amelioration of the immuno-suppressive effect of CMV infection (in clinical transplantation) will likely require more effective prophylaxis and treatment of GvHD in allotransplant recipients.
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Niu, Siwen, Longhe Yang, Tingting Chen, Bihong Hong, Shengxiang Pei, Zongze Shao, and Gaiyun Zhang. "New Monoterpenoids and Polyketides from the Deep-Sea Sediment-Derived Fungus Aspergillus sydowii MCCC 3A00324." Marine Drugs 18, no. 11 (November 17, 2020): 561. http://dx.doi.org/10.3390/md18110561.
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Chemical study of the secondary metabolites of a deep-sea-derived fungus Aspergillus sydowii MCCC 3A00324 led to the isolation of eleven compounds (1–11), including one novel (1) and one new (2) osmane-related monoterpenoids and two undescribed polyketides (3 and 4). The structures of the metabolites were determined by comprehensive analyses of the NMR and HRESIMS spectra, in association with quantum chemical calculations of the 13C NMR, ECD, and specific rotation data for the configurational assignment. Compound 1 possessed a novel monoterpenoid skeleton, biogenetically probably derived from the osmane-type monoperpenoid after the cyclopentane ring cleavage and oxidation reactions. Additionally, compound 3 was the first example of the α-pyrone derivatives bearing two phenyl units at C-3 and C-5, respectively. The anti-inflammatory activities of 1–11 were tested. As a result, compound 6 showed potent inhibitory nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells with an inhibition rate of 94.4% at the concentration of 10 µM. In addition, a plausible biosynthetic pathway for 1 and 2 was also proposed.
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Pritchett, Joshua, Aakash Desai, Bijan J. Borah, Zhuoer Xie, Antoine N. Saliba, Konstantinos Leventakos, Jordan Coffey, et al. "Association of use of remote patient monitoring (RPM) with reduced hospitalizations in cancer patients with COVID-19." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 1503. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.1503.
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1503 Background: Patients with cancer and COVID-19 are at risk for poor clinical outcomes. An established multi-site remote patient monitoring (RPM) service was rapidly adapted to support a novel, interdisciplinary COVID-19 program for outpatient management of patients at high-risk for severe illness. The goal of this study was to assess the impact of the RPM program on clinical outcomes and acute care utilization in cancer patients diagnosed with COVID-19. Methods: This is a cross-sectional analysis following a multi-site prospective observational study performed at Mayo Clinic Cancer Center (MCCC). All adult patients with active cancer – defined as currently receiving cancer-directed therapy or in recent remission on active surveillance – and PCR-confirmed SARS-CoV-2 infection between March 18 and July 31, 2020 were included. RPM was comprised of in-home technology to assess symptoms and physiologic data with centralized nurse and physician oversight. Results: During the study timeframe 224 cancer patients were diagnosed with COVID-19 at MCCC. Initial management included urgent hospitalization (within 48 hours of diagnosis) in 34 patients (15%). Of the remaining 190 patients (85%) initially managed in the outpatient setting, those who did not receive RPM were significantly more likely to experience hospitalization than those receiving RPM (OR 3.6, 95% CI 1.036 to 12.01, P = 0.044). Following balancing of patient characteristics by inverse propensity weighting, rates of hospital admission for RPM and non-RPM patients were 3.1% and 11% respectively, implying that RPM was associated with an 8% reduction in hospital admission rate (-0.077; 95% CI: -0.315 to -0.019, P = 0.009). Use of RPM was also associated with lower rates of prolonged hospitalization, ICU admission, and mortality, though these trends did not reach statistical significance. Conclusions: In the midst of a global pandemic associated with inpatient bed, ventilator, and PPE shortages, the RPM program provided an effective strategy for outpatient clinical management and was associated with decreased rates of hospitalization, ICU admission, and mortality in cancer patients with COVID-19. This care model enabled simultaneous opportunity to mitigate the increased risks of exposure, transmission, and resource utilization associated with conventional care.
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Su, T. T., G. Feger, and P. H. O'Farrell. "Drosophila MCM protein complexes." Molecular Biology of the Cell 7, no. 2 (February 1996): 319–29. http://dx.doi.org/10.1091/mbc.7.2.319.
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MCM genes encode a family of evolutionarily conserved proteins required for DNA replication. In Saccharomyces cerevisiae, where they were first identified, MCM genes interact genetically with each other. Allele specificity in these interactions suggests that MCM proteins physically associate with one another and that this association is essential for function. We describe here an analysis of physical interactions among three Drosophila MCM proteins. Using specific antibodies we detect Drosophila MCMs almost exclusively in 600-kDa protein complexes. Co-immunoprecipitation data demonstrate the existence of at least two distinct types of 600-kDa complexes, one that contains DmCDC46 and one that appears to contain both DmMCM2 and Dpa (a CDC54 homologue). These complexes are stable throughout embryonic division cycles, are resistant to treatments with salt and detergent, and are present during development in tissues undergoing mitotic DNA replication as well as endoreplication. When extracts are prepared under low salt conditions all three MCM proteins co-immunoprecipitate. Consequently, we suggest that the 600-kDa complexes interact in a higher order complex.
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Sharanya Raj, N. L., U. Ajay Sharma, M. L. Revathi Devi, S. M. Purushothama, S. N. Manjunath, and H. B. Shashidhar. "Correlation of red cell indices and hemoglobin concentration with serum ferritin among iron deficiency anemia patients." Biomedicine 39, no. 2 (November 14, 2020): 268–73. http://dx.doi.org/10.51248/.v39i2.194.
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Introduction and Aim: Iron deficiency anemia is the commonest cause of anemia in developing country like India in all age groups. It is most easy to prevent as well as to treat. Its diagnosis and treatment are based on serum ferritin levels in developed countries which is not possible in India at primary healthcare setting. This study was undertaken to explore if red cell indices could replace serum ferritin in detecting iron deficiency.
Materials and Methods: Study of association of red cell indices like Mean Corpuscular Volume (MCV), Mean Corpuscular hemoglobin (MCH), Mean Corpuscular hemoglobin Concentration (MCHC), Red cell Distribution Width (RDW) and Hemoglobin concentration (Hb%) with iron deficiency anemia and the correlation of these Red cell indices and Hb% with serum ferritin was done in 220 anemia patients of all age groups with Hb% <12g/dL.
Results: Descriptive data showed skewed distribution of serum ferritin. Statistically significant reduction in all red cell indices values among iron deficiency anemia patients and statistically significant correlation of all red cell indices values except red cell distribution width with serum ferritin was found.
Conclusion: Unlike developed countries we can use simple estimation of hemoglobin concentration along with red cell indices for diagnosing iron deficiency anemia in primary healthcare setting of India.
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Sistiaga, A., I. Urreta, M. Jodar, A. M. Cobo, J. Emparanza, D. Otaegui, J. J. Poza, et al. "Cognitive/personality pattern and triplet expansion size in adult myotonic dystrophy type 1 (DM1): CTG repeats, cognition and personality in DM1." Psychological Medicine 40, no. 3 (July 23, 2009): 487–95. http://dx.doi.org/10.1017/s0033291709990602.
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BackgroundAlthough central nervous system (CNS) involvement in adult myotonic dystrophy type 1 (DM1) was described long ago, the large number of variables affecting the cognitive and personality profile have made it difficult to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association with the underlying molecular defect.MethodWe examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on cognition and personality adjusted to the remainders.ResultsPatients performed significantly worse than controls in tests measuring executive function (principally cognitive inflexibility) and visuoconstructive ability. In the personality profile, some paranoid and aggressive traits were predominant. Furthermore, there was a significant negative correlation between the CTG expansion size and many of the neuropsychological and personality measures. The molecular defect also correlated with patients' daytime somnolence.ConclusionsBesides muscular symptomatology, there is significant CTG-dependent involvement of the CNS in adult DM1 patients. Our data indicate that the cognitive impairment predominantly affects the fronto-parietal lobe.
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Demeke, Gebreselassie, Getachew Mengistu, Abtie Abebaw, Milkiyas Toru, Molla Yigzaw, Aster Shiferaw, Hylemariam Mihiretie Mengist, and Tebelay Dilnessa. "Effects of intestinal parasite infection on hematological profiles of pregnant women attending antenatal care at Debre Markos Referral Hospital, Northwest Ethiopia: Institution based prospective cohort study." PLOS ONE 16, no. 5 (May 10, 2021): e0250990. http://dx.doi.org/10.1371/journal.pone.0250990.
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Background Intestinal parasitosis is a common disease that causes misery and disability in poor populations. The number of individuals affected is staggering. From two billion peoples who harbor parasites worldwide, 300 million suffer severe morbidity and more than 25% of pregnant women are infected with hookworm, which causes intestinal bleeding and blood loss, and has been most commonly associated with anemia. Intestinal parasite infection during pregnancy has been associated with iron deficiency, maternal anemia, and impaired nutritional status, as well as decreased infant birth weight. Objective This study aimed to assess the effects of intestinal parasite infection on hematological profiles of pregnant women attending antenatal care in Debre Markos Referral Hospital from December 2017 to February 2019. Method A prospective cohort study design was conducted among 94 intestinal parasite-infected pregnant women as an exposed group and 187 pregnant women free from intestinal parasite were used as a control group. The effect of intestinal parasites on hematological profiles of pregnant women was assessed at Debre Markos Referral Hospital antenatal care ward. Socio-demographic data and nutrition status were assessed by using structured questionnaires and mid-upper arm circumference (MUAC), respectively. Two ml of venous blood and 2 gm of stool samples were collected to analyze the hematological profiles and detect intestinal parasites, respectively. Wet mount and formol-ether concentration (FEC) techniques were used to detect intestinal parasites. Hematological profile was analyzed using Mind ray BC-3000 plus instrument. Data were double entered into EpiData version 3.1 software and exported to SPSS version 24 software for analysis. Results were presented using tables and graphs. Associations of hemoglobin levels with intestinal parasitic infections were determined using binary logistic regression models. P≤0.05 was considered statistically significant. The mean hematological profile difference between parasite-infected and parasite-free pregnant women was computed using independent t-test. Results In the present study, the predominant parasites identified were Entamoeba histolytica, hookworm, Giardia lamblia, Schistosoma mansoni, and Ascaris lumbricoides. About 8.2% of intestinal parasite-infected pregnant women had mild anemia while 4% had moderate anemia. Only 1.2% of intestinal parasite-free pregnant women developed moderate anemia. The mean HGB, HCT, MCV, MCH, and MCHC values of intestinal parasite-infected pregnant women were 12.8g/dl, 38.2%, 94.7fl, 33.1pg and 34.7g/dl, respectively. But the mean HGB, HCT, MCV, MCH and MCHC values of pregnant women who were free from intestinal parasites were 14.4 g/dl, 39.8%, 94.9fl, 33.9pg and 35.5g/dl, respectively. Anemia was strongly associated with hookworm (AOR = 21.29, 95%CI: 8.28–54.75, P<0.001), S.mansoni (AOR = 63.73, 95% CI: 19.15–212, P<0.001) and A.lumbricoide (AOR = 14.12, 95% CI 3.28–60.65, P<0.001). Conclusion Intestinal parasitic infection in pregnant women caused adverse impact on hematological profiles and was an independent predictor of anemia. Intestinal parasitic infection significantly decreased pregnant the level of HGB, HCT, MCV, MCH, and MCHC values. To minimize maternal anemia deworming could be good before pregnancy.
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Dzehverovic, Mirela, Anesa Ahatovic, Naris Pojskic, Naida Lojo-Kadric, Amela Pilav, Damir Marjanovic, and Jasmina Cakar. "Decrease in body mass index: Personal genotyping, individual diet, and exercise plan." Journal of Health Sciences 7, no. 2 (September 25, 2017): 91–98. http://dx.doi.org/10.17532/jhsci.2017.432.
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Introduction: Single nucleotide polymorphisms (SNPs) have lately been used for prediction of metabolic processes that may be related to obesity. The aim of our study was to examine the association of SNPs of several genes with obesity and physical activity in 18 healthy volunteers.
Methods: We used buccal swabs to collect and extract DNA from 18 volunteers. Pyrosequencing was used for molecular analysis of 13 polymorphisms in 10 genes (APOA2, MTHFR, MCM6, peroxisome proliferators-activated receptor gamma, FABP2, beta-2-adrenergic receptor (ADRB)2, ADRB3, A-actinin-3, angiotensin-converting enzyme, and FUT2). The volunteers’ personal data included body mass index (BMI), dietary practice and information on daily fitness and workout routine. Association between the 13 observed gene polymorphisms and individual BMI status (normal or overweight) was analyzed. Results of the DNA analysis were used for the expert evaluation by nutritionists and physiologists to obtain optimal regulation of nutrition and exercise. The volunteers had a dietary and fitness program for 12 months which they tracked by filling in a suitable study form.
Results: 14 volunteers had a moderate genetic predisposition for abdominal adipose-tissue accumulation, while 4 of them had genotypes not associated with abdominal fat tissue accumulation. A statistically significant difference was found between the value of BMI before and after the implementation of personalized training and nutrition plan within the group of overweight volunteers (paired sample t=3.382; p = 0.006; exact p = 0.015). The single-locus F-test showed no association between the gene polymorphisms and BMI values. In addition, no correlation was detected between the gene polymorphisms and amount of BMI reduction prior and after the implementation of the personalized training and nutrition plan within the overweighed group of volunteers.
Conclusion: Optimal nutrition and training plan are crucial for the BMI reduction as observed in the overweighed volunteers after the 12-month personalized training and individualized nutrition plan. However, the analyzed polymorphisms were not significantly associated with the obesity in this study.
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Arai, Hiroyuki, Yi Xiao, Jingyuan Wang, Francesca Battaglin, Natsuko Kawanishi, Priya Jayachandran, Shivani Soni, et al. "Germline polymorphisms in genes maintaining replication fork to predict the efficacy of oxaliplatin and irinotecan in metastatic colorectal cancer (mCRC) patients enrolled in MAVERICC trial." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 3139. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.3139.
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3139 Background: Protection of replication forks is critical for the survival of cancer cells. Chemotherapeutic drugs such as oxaliplatin and irinotecan can impede the progression of replication forks by inducing DNA lesions, which cause fork collapse and generate double-strand breaks. We hypothesized that functional genetic variants in genes involved in the maintenance of replication forks may predict the efficacy of cytotoxic drugs in mCRC patients. Methods: We analyzed genomic and clinical data from MAVERICC, a phase II trial which compared mFOLFOX6 and FOLFIRI in combination with bevacizumab in untreated mCRC patients. Genomic DNA extracted from blood samples was genotyped using an OncoArray (Illumina, Inc., San Diego, CA, USA). Candidate six missense single nucleotide polymorphisms (SNPs) ( SLFN11 rs9898983, SLFN11 rs12453150, RPA1 rs5030749, MCM3 rs2230240, TIMELESS rs2291739, and TIMELESS rs774047) were tested for association with progression-free survival (PFS) and overall survival (OS), using Cox proportional hazards model. To confirm the predictive value, the treatment-by-SNP interaction was tested. Results: A total of 324 patients were available for the SNP analyses (mFOLFOX6 plus bevacizumab arm [OHP arm]: n = 161; FOLFIRI plus bevacizumab arm [IRI arm]: n = 163). In the OHP arm, univariable analysis showed a significantly better PFS in patients with G/G genotype of TIMELESS rs2291739 compared to those with any A allele, and in patients with T/T genotype of TIMELESS rs774047 compared to those with any C allele. However, neither of these SNP’s associations were confirmed by multivariable analysis: TIMELESS rs2291739 (any A allele vs G/G, hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.31–1.17, p = 0.12) and TIMELESS rs774047 (any C allele vs T/T, HR = 0.74, 95% CI = 0.41–1.36, p = 0.33). In the IRI arm, univariable analysis showed a significantly worse OS in patients with G/G genotype of TIMELESS rs2291739 compared to those with any A allele, and in patients with T/T genotype of TIMELESS rs774047 compared to those with any C allele. Multivariable analysis confirmed the significant associations in these SNPs: TIMELESS rs2291739 (any A allele vs G/G, HR = 3.06, 95% CI = 1.49–6.25, p < 0.01) and TIMELESS rs774047 (any C allele vs T/T, HR = 2.95, 95% CI = 1.43–6.08, p < 0.01). Treatment-by-SNP interaction test confirmed the significant predictive value of both SNPs, both on PFS and OS. Conclusions: Germline polymorphisms in the TIMELESS gene involved in the protection of replication forks may predict efficacy of oxaliplatin and irinotecan in mCRC patients. Our novel findings warrant further validation studies.
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Blazhko, N. V., S. Kh Vyshegurov, A. S. Donchenko, K. S. Shatokhin, T. I. Krytsyna, and V. A. Ryabinina. "Association of haplotypes for SNPs in the LTR regions of bovine leukemia virus with hematological indices of cattle." Vavilov Journal of Genetics and Breeding 23, no. 3 (May 14, 2019): 262–69. http://dx.doi.org/10.18699/vj19.491.
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Molecular typing of BLV samples isolated from Holsteinized Russian Black Pied cattle was carried out, and various cytofluorometric and morphological blood indices were examined. We performed the total count of white blood cells (WBC), lymphocyte (lymf), granulocyte (gran), monocyte (mon), red blood cell (RBC), hemoglobin (HGB), hematocrit (HTC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet crit count (PCT). The LTR-region of BLV was haplotyped. Only viruses of haplotypes I (0.33±0.03) and III (0.67±0.03) of the eight possible were detected. The ratio of hematologically sick, healthy, and suspected carriers of BLV of haplotypes I and II was comparable with the results of other researchers. The numbers of leukocytes, erythrocytes and platelets in the blood of carriers of haplotype III exceeded the corresponding parameters of cattle affected by the virus of haplotype I. It is interesting to note that the difference in the hemolytic status of animals was manifested not only by the concentration of leukocytes as direct immune agents but also by the count of erythrocytes and platelets, which are not directly involved in the immune response. The number of particles of haplotype III of the BLV circulating in the blood of infected individuals exceeded that of the carriers of haplotype I. In this connection, an assumption was made about the evolutionary advantage of the more virulent haplotype III. However, the results of our own research in conjunction with the data of other scientists indicate that the high virulence of individual virus strains is a consequence of the tendency to implement the maximum possible intensity of the synthesis of virus particles but not of the high damaging effect alone. It is shown that high lethality is evolutionarily disadvantageous for viruses, since the extinction of the carrier as a biological species is fraught with the disappearance of the virus itself.
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Ghosal, Sharmistha. "Relationship of Iron Deficiency Anemia with Simple Febrile Seizure in Children." Journal of Bangladesh College of Physicians and Surgeons 35, no. 2 (July 29, 2017): 75–79. http://dx.doi.org/10.3329/jbcps.v35i2.33367.
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Background and objective: Febrile Seizure (FS) is the commonest seizure disorder among under 5 children. Iron deficiency is a documented risk factor of FS and as the data about the relationship of iron deficiency with FS among Bangladeshi children is scanty, this study was undertaken to assess the association of Serum Ferritin to simple FS.Materials and Methods: This case control study was conducted at the department of pediatrics of SSMC & Mitford Hospital during 7th May 2011 to 6th January 2012 on consecutive 120 children aged between five months to six years who fulfilled the inclusion criteria were considered as cases. Similar number of age and sex matched children admitted with fever without seizures were taken as controls. All candidates were gone through CBC with RBC indices and serum ferritin and iron deficiency anemia was diagnosed on the basis of mentioned tests.Results: The results showed that majority of the cases were male (66.7%) and most of them were between 13-24 months of age (51.7%). Mean duration of convulsion was less than 5 minutes in 70% of the cases. Level of Hb was low in both the cases and controls but the other RBC indices for anemia like MCV, MCH, MCHC and serum ferritin were significantly lower among the febrile seizures group in comparison to controls. The chi-square test is indicated as a significant difference between two groups and odds ratio is 6.0 which signifies that febrile seizure group were 6.0 times more likely to develop iron deficiency anemia compared to control group.Conclusion: The findings suggest that children with febrile seizure have association with iron deficiency anemia (which is evident by microcytic hypochromic anemia and low serum ferritin level) .This means low serum ferritin and presence of anemia can serve as a risk factor for febrile seizure in children.J Bangladesh Coll Phys Surg 2017; 35(2): 75-79
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Buzás, György Miklós. "A laktózintoleranciáról: Múlt és jelen – I. rész." Orvosi Hetilap 156, no. 38 (September 2015): 1532–39. http://dx.doi.org/10.1556/650.2015.30261.
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Lactose intolerance is the most prevalent intestinal malabsorption disorder. After presentation of its history, the author describes the emergence of lactose intolerance during the evolution of species, and the biochemistry of lactose as well as features of human and bacterial lactase enzymes are then described. The unequal distribution of lactose intolerance in different continents and population is discussed, followed by presentation of past and present prevalence data in Hungary. Adult-type hypolactasia is caused by a polymorphism of the MCM6 gene located upstream from the lactase gene on the long arm of the chromosome 2. It can be determined with the polymerase chain reaction. The intestinal symptoms of lactose intolerance are well known, but its extra-intestinal manifestations are less recognised. Invasive diagnostic methods (determination of lactase activity from small intestinal biopsies, lactose tolerance test), are accurate, but have been replaced by the non-invasive methods; their gold standard is the H2 breath test. Genetic testing is being used more and more frequently in Hungary too, and, presumably, the methane breath test will be also available in the near future. Lactose intolerance can be accompanied by inflammatory bowel diseases, coeliac disease and irritable bowel syndrome; it could be established whether this association is causal or not in order to start a correct diet and therapy. Orv. Hetil., 2015, 156(38), 1532–1539.
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Sever-Chroneos, Zvjezdana, Steven P. Angus, Anne F. Fribourg, Huajing Wan, Ivan Todorov, Karen E. Knudsen, and Erik S. Knudsen. "Retinoblastoma Tumor Suppressor Protein Signals through Inhibition of Cyclin-Dependent Kinase 2 Activity To Disrupt PCNA Function in S Phase." Molecular and Cellular Biology 21, no. 12 (June 15, 2001): 4032–45. http://dx.doi.org/10.1128/mcb.21.12.4032-4045.2001.
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ABSTRACT The retinoblastoma tumor suppressor protein (RB) is a negative regulator of the cell cycle that inhibits both G1 and S-phase progression. While RB-mediated G1 inhibition has been extensively studied, the mechanism utilized for S-phase inhibition is unknown. To delineate the mechanism through which RB inhibits DNA replication, we generated cells which inducibly express a constitutively active allele of RB (PSM-RB). We show that RB-mediated S-phase inhibition does not inhibit the chromatin binding function of MCM2 or RPA, suggesting that RB does not regulate the prereplication complex or disrupt early initiation events. However, activation of RB in S-phase cells disrupts the chromatin tethering of PCNA, a requisite component of the DNA replication machinery. The action of RB was S phase specific and did not inhibit the DNA damage-mediated association of PCNA with chromatin. We also show that RB-mediated PCNA inhibition was dependent on downregulation of CDK2 activity, which was achieved through the downregulation of cyclin A. Importantly, restoration of cyclin-dependent kinase 2 (CDK2)–cyclin A and thus PCNA activity partially restored S-phase progression in the presence of active RB. Therefore, the data presented identify RB-mediated regulation of PCNA activity via CDK2 attenuation as a mechanism through which RB regulates S-phase progression. Together, these findings identify a novel pathway of RB-mediated replication inhibition.
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Sabu, Joel. "A correlative study of copper, iron, zinc and haematological parameters in oral cancer patients." MedPulse International Journal of Biochemistry 19, no. 2 (2021): 22–25. http://dx.doi.org/10.26611/10021923.
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Background: Alteration in levels of copper, iron and zinc variate the enzymatic actions in our body and thereby play a major role in etiopathogenesis of oral carcinogenesis. Aim of the study: The present study was mainly aimed to estimate, compare and correlate the serum levels of copper, iron and zinc with haematological parameters in oral cancer patients in comparison to normal controls. Methods: The collected serum of cases and controls were analyzed by using standard spectrophotometric methods in spectrophotometer analyzer and the data obtained was analysed and represented as Mean ± SD, mean difference was analyzed by Student’s T-test and Chi- square test for significance and strength of association by Karl Pearson’s correlation using SPSSv23 software. Results: Mean serum level of iron was significantly lower and the levels of zinc and copper in patients with oral cancerous lesions were significantly higher than that of healthy individuals. Pearson’s r data analysis, revealed a significant negative correlation between iron with platelets, and MCHC (Mean Corpuscular Haemoglobin Concentration). A significant positive correlation was seen between iron with haemoglobin and lymphocytes; between copper with leucocytes. Conclusions: The serum levels of zinc and copper in group I were significantly higher when compared to controls. There was a significant lower serum level of iron in Group-I when compared to controls. A significant correlation was seen in between serum trace elements and haematological parameters in oral cancer. This suggests the involvement of trace elements in variations of haematological parameters in the pathogenesis of oral carcinogenesis.
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Khurana, Sharad, Michael G. Heckman, Jordan Cochuyt, Fiona E. Craig, Zaid Abdel Rahman, Patricia Greipp, Lisa Z. Sproat, Mark Litzow, James M. Foran, and Liuyan Jiang. "Identification of Targetable Tumor Associated Proteins in Adult T-Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL) Including a Novel CC-Chemokine 4 (CCR4)-Positive T-ALL/LBL with Unique Immunophenotype." Blood 134, Supplement_1 (November 13, 2019): 5210. http://dx.doi.org/10.1182/blood-2019-123286.
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Introduction There have been few recent therapeutic advances in T-acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), a rare and aggressive malignancy. Intensive chemotherapy +/- allogeneic transplantation (AlloHCT) can effect cure, realized by only a minority of adults. In distinction to B-ALL, there have been no safe/effective targeted therapies developed in T-ALL/LBL. We therefore performed a focused tissue array to identify novel tumor proteins, including CCR4; evaluated together with established immunophenotypic (IP) T-ALL/LBL subtypes [early-T-precursor (ETP), early non-ETP (Pre/Pro-T), common & late thymocyte]. We evaluated the clinical phenotype and outcome together with clinical and epidemiologic data in patients diagnosed at the 3-site Mayo Clinic Cancer Center (MCCC: Rochester, MN; Phoenix, AZ; and Jacksonville, FL). Methods Following IRB approval, we identified 50 consecutive T-ALL/LBL patients from 1997 -2019 diagnosed at the 3-site MCCC. Available remnant leukemia/lymphoma paraffin blocks were identified (n=28). Using immunohistochemistry (IHC) we evaluated expression of leukemic antigens of interest (CCR4, CD47, BCL2, BCL6, PD-L1, CD38 and CD123); these were selected based on clinical availability of novel targeted agents, approved or in development for other indications. Tissue array studies were performed and interpreted by a single hematopathologist (L.J) blinded to clinical data, using positive and negative controls, according to standard techniques. We also evaluated the clinical and epidemiological parameters, including different IP subtypes [ETP: CD1a-, sCD3- & CD8-, Pre/Pro-T: CD1a-, sCD3- & CD8+ or CD8- (11 marker T-ALL IP score was used to distinguish CD8- ETP vs. Pre/Pro-T), thymic: CD1a+ and mature: CD1a- & sCD3+] (Khogeer et al., Br J Haematol., 2019) & the presence of the unique MLLT10-PICALM fusion (n=6), as well as therapy and outcome. Comparisons of characteristics and outcomes of interest were made using a Wilcoxon rank sum test (continuous characteristics) or Fisher's exact test (categorical characteristics), unadjusted Cox proportional hazards regression models (overall survival), or unadjusted logistic regression models (complete remission after first line treatment). Results We identified the expression of novel targetable tissue proteins in all adult T-ALL/LBL cases [Table 1]. BCL2, CD38 & CD47 were expressed in majority of the cases, and CCR4 [Fig. 1] was expressed in 11/28 (39.3%) cases. CCR4 expression was significantly more common in the Pre/Pro-T (75%) vs. other IP subtypes (19%) (p=0.011); there was no other association of CCR4 expression with clinical characteristics/outcomes. We also observed differences in T-ALL vs. T-LBL, specifically T-ALL patients were more likely to be male (71% vs. LBL 38.9%, p=0.038). Surprisingly, T-LBL patients were more likely to have a family history of leukemia/lymphoma (41.2% vs. T-ALL 0%, p<0.001). In addition, a significantly different distribution of IP subtype in T-LBL was noted [Table 2]. Not surprisingly, T-LBL patients were more likely to receive 1st line Hyper-CVAD therapy (88.2% v. T-ALL 43.3%, p=0.005), & had a longer delay from diagnosis to initiation of therapy (median 14 vs. 4 days, p=0.012), however this did not appear to impact clinical outcome. In contrast, we observed an important association of IP subtype with outcome after therapy, including complete remission (p=0.035), & a trend suggesting differences in survival (p=0.069) [Table 3]. However, MLLT10-PICALM was not associated with any unique clinical features or with outcome (death, p=0.85; CR, p=0.98), although 4/6 patients underwent AlloHCT, suggesting an important role of AlloHCT in this subgroup. No other significant association of epidemiologic risk factors with phenotype or outcome was noted. Conclusion Using focused tissue array we have identified expression of tumor associated proteins in T-ALL/LBL including CCR4 (Pre/Pro-T IP) & others, which may be targets of therapeutic agents like mogamulizumab. Furthermore, our analysis demonstrates an important clinical impact of IP subtype in T-ALL/LBL, as well as important clinical & therapeutic differences in T-ALL vs. LBL. This study will help guide development of targeted clinical trials in T-ALL/LBL (CCR4 trial already in development). Further analyses are planned to determine the clinical & epidemiologic association of genetic lesions in this cohort. Disclosures Foran: Agios: Honoraria, Research Funding.
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Park, Jae Hong, Bianca Santomasso, Isabelle Riviere, Brigitte Senechal, Xiuyan Wang, Terence Purdon, Yongzeng Wang, et al. "Baseline and early post-treatment clinical and laboratory factors associated with severe neurotoxicity following 19-28z CAR T cells in adult patients with relapsed B-ALL." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 7024. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.7024.
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7024 Background: CD19-specific chimeric antigen receptor (CAR) modified T cells produce high anti-tumor activity in relapsed or refractory (R/R) ALL, but can be associated with cytokine release syndrome (CRS) and neurotoxicity (NTX). Herein, we report baseline and post-treatment clinical and laboratory factors associated with severe NTX (≥Grade 3) in our phase I clinical trial of CD19-specific 19-28z CAR T cells for adult patients (pts) with R/R B-ALL (NCT01044069). Methods: 51 adult pts with R/R B-ALL were treated with 19-28z CAR T cells following conditioning chemotherapy at MSKCC. In order to identify clinical and serum biomarkers associated with severe NTX (sNTX), we examined demographic, treatment, and clinical blood parameters as well as in vivo CAR T expansion and serum cytokines, and performed univariate and multivariate analysis. Results: In this cohort of ALL pts, 20, 8, 2, 18 and 3 pts experienced Gr 0, 1, 2, 3, and 4 NTX, respectively. No pt developed grade 5 NTX. Disease burden (≥50% blasts) at the time of T cell infusion (p = 0.0045) and post-treatment ≥Gr3 CRS (p = 0.0010) were significantly associated with sNTX, but we found no association with age, weight, T cell dose, choice of conditioning chemotherapy (Flu/Cy s. Cy), and prior lines of treatment. Among the clinical and blood parameters, fever, low PLT, high ferritin and MCHC as well as elevated GM-CSF, IFNγ, IL-15, IL-5, IL-10, IL-2 at day 3 of T cell infusion at day 3 of T cell infusion were significantly associated with sNTX (all p < 0.01). While some of these cytokines were also elevated in severe CRS cases, IL-5 and IL-2 at day 3 were unique to sNTX. Furthermore, in vivo peak CAR T expansion at day 7 (p = 0.0001) significantly correlated with sNTX (p < 0.01). Lastly, multivariate analysis revealed baseline PLT < 60 or MCHC > 33.2% and morphologic disease ( > 5% blasts) has 95% sensitivity and 70% specificity of identifying sNTX pts. Conclusions: These data provide a characterization of early clinical and serum biomarkers of sNTX in adult pts receiving 19-28z CAR T cells and should help identify appropriate pts for early intervention strategy to mitigate NTX. Clinical trial information: NCT01044069.
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Sloan, J. A., H. Liu, D. J. Sargent, D. Satele, P. L. Schaefer, M. Y. Halyard, A. Grothey, et al. "A patient-level pooled analysis of the prognostic significance of baseline fatigue for overall survival (OS) among 3,915 patients participating in 43 North Central Cancer Treatment Group (NCCTG) and Mayo Clinic Cancer Center (MC) oncology clinical trials." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 9599. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.9599.
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9599 Background: We have previously identified overall a single-item measure for baseline quality of life (QOL) as a strong prognostic factor for survival (Tan, ASCO 2008), and that fatigue was an important component of patient QOL (Sloan, 2007). To explore whether patient-reported fatigue was supplemental or redundant to the prognostic information of overall QOL, we performed a patient-level pooled analysis of 43 NCCTG and MCCC oncology clinical trials of the effect of baseline fatigue on OS. Methods: 3,915 patients participating in 43 trials provided data at baseline for fatigue on a single-item 0–100 point scale. OS was tested for association with clinically deficient fatigue (CDF, score 0–50, n=1,497) vs not clinically deficient fatigue (nCDF, score 51–100, n=2,418). Cox proportional hazards models adjusted for the effects of overall QOL, performance score, race, disease site, age and gender. Results: Baseline fatigue was a strong predictor of OS for the entire patient cohort (CDF vs. nCDF: 31.5 mos vs >83.9 mos, p<0.0001). The effect sizes were consistent across different disease sites (GI, esophageal, head and neck, prostate, lung, breast and others). After controlling for covariates, including performance status and overall QOL, baseline fatigue remained a strong prognostic factor in multivariate models (CDF vs. nCDF: HR=1.23, p=0.02). Conclusions: Fatigue is a strong prognostic factor for OS independent of overall QOL and PS in a wide variety of oncology patient populations. Single-item measures of overall QOL and fatigue can help to identify vulnerable subpopulations among cancer patients. No significant financial relationships to disclose.
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Adam, Nassreldeen. "Hematological Parameters in Sudanese Type-2 Diabetes Mellitus." Biomedical Research and Clinical Reviews 4, no. 3 (July 23, 2021): 01–04. http://dx.doi.org/10.31579/2692-9406/070.
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Background: Diabetes mellitus is a complex concept for a spectrum of disorders characterized by hyperglycemia and a variety of complications, comprising metabolic and cellular disturbances that lead to vascular complications. The objective of this project was to correlate type 2 diabetes patients to healthy controls in aspects of hematological indices and their association with demographic data. Materials and Methods: From May to September 2016, a case-control analysis has been performed in Khartoum, Sudan. 154 participants were enrolled in this study. 104 participant were diabetic type 2 and 50 were apparently healthy as control group to find out any variations in hematological parameters HbA1C and CBC: (Hb, WBCs & differential, RBCs& indices and PLTs, hematocrit (HCT) among type 2 diabetic patients. Blood was gathered in EDTA containers. HbA1C measured using i-CHROMATM and complete blood count using the Sysmex® Kx21-N hematological analyzer. Before samples collection, each participant gave their informed consent, which had been approved by the Ministry of Health's ethical committee. The Statistical Package for Social Sciences (SPSS) SPSS version 20 was used. The meaning of the discrepancies was assessed using the Crosstab test. p- Value is significant at P< 0.05. Results: T2DM patients had a statically significant in white blood cells, neutrophils, and lymphocytes as comparison to the control group P<0.05. There was no considerable difference in red blood cell count, Hb, Hct, MCV, MCH, MCHC, RDW, Platelets count, MPV, and PDW between the two classes P> 0.05. Conclusion: T2DM patients had relatively increased levels of white blood cells, neutrophils, and lymphocytes than the control group (P<0.05).
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Jegede, Feyisayo E., Tinuade I. Oyeyi, Surajudeen A. Abdulrahman, and Henry A. Mbah. "Malaria Parasite Density as a Predictor of Hematological Parameter Changes among HIV Infected Adults Attending Two Antiretroviral Treatment Clinics in Kano, Northwest Nigeria." Journal of Tropical Medicine 2020 (April 27, 2020): 1–9. http://dx.doi.org/10.1155/2020/3210585.
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Background. Despite public health significance of dual infections of human immunodeficiency virus (HIV) and malaria in developing countries like Nigeria, information on the association between malaria parasite density count (MPDC) and hematological parameter changes among HIV-infected individuals is rarely available. Objectives. To evaluate burden of HIV and malaria dual infections and assess the predictive association of MPDC with hematological parameter changes among HIV infected adults attending two antiretroviral treatment clinics in Kano, Nigeria. Methodology. This was a cross-sectional study consisting of 1521 consented participants randomly selected between June 2015 and May 2016. Participants’ basic characteristics and clinical details were collected using a pretested and validated standardized questionnaire. Collected venous blood was analyzed for malaria by rapid testing and microscopy including malaria parasite density; hematological parameters were estimated using a Sysmex XP-300 autoanalyzer. Data was reviewed, cleaned, and analyzed using SPSS software version 23.0. Mean hematological parameters and HIV/malaria status were compared using the independent t-test; hematological parameters and MPDC relationship was tested by simple linear regression analysis. Statistically significant difference at probability of <0.05 was considered for all variables. Results. The majority (70.6%) of the participants were females. Mean (SD) age was 37.30 ± (10.41) years and ranged from 18 to 78 years. 25.4% of participants had dual infection, 99% due to Plasmodium falciparum species. Mean MPDC was 265 ± 31.8 (SD) cells/μl and ranged from 20 to 2500 cells/μl. Dual infection was highest (37.5%) among respondents in the age group ≥60 years. Prevalence was similar among other age groups (p=0.165) and gender (p=0.942). Of the 16 hematological parameters evaluated, 11 showed significant difference between HIV mono-infected and dual infected participants. Of the 11 parameters, only 7 (Hb, MCHC, red cells count, neutrophil and lymphocyte percentage, absolute lymphocyte count, and red cell distribution width) were significantly predictive of changes with respect to MPDC. Conclusions. MPDC was significantly predictive of changes in 7 hematological parameters among dual infected participants in these settings. In routine malaria diagnosis, MPDC determination with respect to changes in some hematological parameters should be considered in ART programs for improved patient management.
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Al-Shdayfat, Noha Mohammad. "Emotional Abuse among Syrian Refugee Women in Jordan." Global Journal of Health Science 9, no. 3 (February 1, 2017): 237. http://dx.doi.org/10.5539/gjhs.v9n3p237.
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BACKGROUND: Violence against women is a worldwide issue. Emotional abuse of women is the second most common form of abuse after physical abuse. Thus, this issue needs focus and attention especially among disadvantaged communities such as refugees.OBJECTIVE: This study aimed to investigate the prevalence of emotional abuse among Syrian refugee women in Jordan.METHODS: A descriptive cross-sectional study was conducted using a convenient sample of 182 Syrian refugee women residing in Mafraq Governorate. Participants were recruited from Maternal & Child Health Centers (MCHC) across the governorate. A validated Arabic version of the NorVold Domestic Abuse Questionnaire (NORAQ) was used to collect data from the study participants.RESULTS: Participants’ ages ranged from 19 to 55 years, (mean age ± 30.2; SD ± 8.9 years). Forty four percent of the participants reported experiencing emotional abuse in the preceding year prior the evaluation. The lifetime prevalence of emotional abuse was 51.6%. About 21.4% of married refugees surveyed reported emotional abuse from their husbands. Thirteen percent of the married participant reported being emotionally abused by their brothers. Twelve of the unmarried participants reported that the perpetrators were family members (4 fathers, 7 brothers, and 1 mother). Logistic regression model revealed that Syrian refugee women who are married, live within large families, reside in urban areas, and have lower educational levels are more likely to suffer emotional abuse. A significant association was found between exposure to emotional abuse and poor mental health, including depression, insomnia and feelings of anguish.CONCLUSION: High prevalence rate of life time abuse was revealed by this study. Overall, findings suggest that improving socio-demographic circumstances (i e education) would reduce their vulnerability to emotional abuse. This study may guide both future research and current efforts to combat emotional violence amongst Syrian refugee women.
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Ashley-Koch, Allison E., Laura M. De Castro, Felicia Lennon-Graham, Jude Jonassaint, Terry L. Jackson, Jennifer Price, Jason Galloway, et al. "Clinical and Genetic Profiles of the Aging Sickle Cell Patient." Blood 106, no. 11 (November 16, 2005): 75. http://dx.doi.org/10.1182/blood.v106.11.75.75.
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Abstract The life expectancy of many patients with sickle cell disease (SCD) is well into the 5th and 6th decade, but this remains extremely variable. Little is known about the biological factors that protect certain SCD patients from early demise while others never reach mid-adulthood. Recently, McKerrell and colleagues (2004) compared the clinical and laboratory profiles of SCD patients aged 40 years and over with SCD patients who were between 21 and 30 years of age. Similarly, we have compared clinical and genetic correlates of older SCD patients (50 years and over) with those of younger patients (18–30 years). Among 514 patients in our total study population, 49 (10%) were categorized as “older” and 194 (38%) were categorized as “younger.” Older SCD patients had lower hemoglobin (older: 7.8 ± 1.1 vs. younger: 8.5 ± 1.2, p=0.004), platelet count (older: 372 ± 126 vs. younger: 460 ± 225, p=0.02), MCV (older: 92 ± 12 vs. younger: 89 ± 9, p=0.08), MCHC (older: 33.6 ± 1.4 vs. younger: 34.3 ± 1.8, p=0.05), and WBC (older: 10.2 ± 2.7 vs. younger: 13.1 ± 4.1, p<0.001). Older patients also had lower total bilirubin (p=0.01), and increased alkaline phosphatase (p=0.0002) and creatinine (p=0.0002), which was associated with poorer creatinine clearance (p<0.0001). The older SCD patients also had increased systolic (p<0.0001) and diastolic (p=0.008) blood pressure, decreased O2 saturation (p=0.03), and a history of fewer pain episodes per year requiring medical treatment (p<0.0001). Many of our findings are consistent with those of McKerrell et al. (2004). In order to identify genetic factors associated with longevity in SCD, we examined 155 SNPs in a total of 41 genes, primarily involved in red blood cell adhesion and inflammation pathways. Chi Square tests of association were constructed for the genotypes of each SNP with the two clinical categories: “older” and “younger.” When the number of rare homozygotes was less than 5 individuals, we combined those individuals with the heterozygote individuals for analysis. All p-values are uncorrected for multiple testing. We found putative associations with 5 SNPs in 3 genes. Three non-coding SNPs in Klotho, not in linkage disequilibrium, exhibited different genotype frequencies in the older versus younger SCD patients (p=0.007, p=0.01 and p=0.01). Similarly, a single non-coding SNP in NOS2A (p=0.02) and TGFBR2 (p=0.02) also exhibited significantly different genotype frequencies in the older versus younger patients. These data support the clinical findings in aging SCD patients reported by McKerrell and colleagues (2004), and they also suggest that genetic factors contribute to variability in longevity in SCD. Interestingly, multiple SNPs in Klotho exhibited differing genotype frequencies in older versus younger patients. Mutations in Klotho have been previously associated with aging-related phenotypes in mice. A better understanding of the biological mechanisms associated with longevity in SCD may help identify those at risk for early demise and in need of more specialized medical care.
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Gynn, Matthew, Mario Fidanza, Sumin Jo, Soren Gantt, Tobias R. Kollmann, and Gregor S. D. Reid. "Differential Effects of Pathogenic and Non-Pathogenic Early-Life Exposures on Acute Lymphoblastic Leukemia Progression in Eμ-RET Mice." Blood 132, Supplement 1 (November 29, 2018): 1422. http://dx.doi.org/10.1182/blood-2018-99-119718.
Full textAbstract:
Abstract B cell precursor acute lymphoblastic leukemia (B-ALL), the most common cancer in children, is a multi-step disease that is initiated in utero; although B-ALL has an incidence peak at 3-5 years of age, the majority of these children have pre-leukemic cells detectable at birth. Notably, however, up to 5% of newborns have detectable leukemia-initiating genetic abnormalities in their blood, but most of these infants go on to live healthy lives. Identifying the mechanisms that inhibit or drive B-ALL progression has the potential to inform new therapeutic or preventative strategies. Infection has been identified as a potential leukemia progression modifier to explain the discordance between the number of children with pre-leukemia and the number who develop B-ALL. While epidemiological studies have identified the timing of infection as a critical variable, the mechanisms underlying this association remain unknown. The early incidence peak is dominated by the ETV6-RUNX1 translocation-positive and high hyperdiploid subgroups, which together account for ~50% of pediatric B-ALL cases. We have previously reported the ability of immune stimulation with infection-associated toll-like receptor agonists to reduce pre-leukemic cell burden and delay leukemia onset in Eμ-RET mice, in which hyperdiploid B-ALL is fully penetrant. Furthermore, exposure of Eμ-RET mice to mild infections with Listeria monocytogenes (Lm), Murine herpesvirus 68 (MHV) or Murine cytomegalovirus (MCMV) induces a profound, age-dependent depletion of pre-leukemia cells, with neonatal mice, but not adults, exhibiting reduced leukemia progression after infection. Here, we extend this work by evaluating the influence of Saccharomyces cerevisiae (Sc) on leukemia development, hypothesizing that exposures to non-pathogenic commensal organisms would induce a similar protective immune activity. Using our established methodology, Eμ-RET mice were exposed to pathogenic or non-pathogenic organisms at six days of age by intraperitoneal injection (Lm, MCMV, Sc) or intranasally (MHV), and evaluated for pre-leukemic cell burden eight days later. In contrast to the response to pathogens, exposure of neonates to Sc did not result in a reduction of pre-leukemic cell numbers, even after inoculation with significantly higher numbers of yeast particles. The depletion of pre-leukemia cells induced by infection with pathogenic organisms was dependent on the presence of both γδ T cells and NK cells, with the latter population exerting direct cytotoxicity against B-ALL cells. Consistent with a failure to induce pre-leukemia depletion, Sc exposure achieved significantly less activation of γδ T cells and did not activate NK cells at all in neonatal Eμ-RET mice. Overall, our results reveal the primacy of the γδ T/NK cell response axis for the depletion of pre-leukemic cells after early-life infection and thus identify a novel immune response pathway with the potential to prevent ALL progression in children. Furthermore, these data indicate that not all age-associated exposures are capable of driving an immune response that reduces the risk of leukemia, with the dietary commensal Saccharomyces cerevisiae failing to generate a protective response in neonatal mice. This study significantly enhances our mechanistic understanding of immune-mediated modification of B-ALL progression. Disclosures No relevant conflicts of interest to declare.