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Anthracnose (ANT) and angular leaf spot (ALS) are significant diseases in common bean, leading to considerable yield losses under specific environmental conditions. The California Dark Red Kidney (CDRK) bean cultivar is known for its resistance to multiple races of both pathogens. Previous studies have identified the CoPv01CDRK/PhgPv01CDRK resistance loci on chromosome Pv01. Here, we evaluated the expression levels of ten candidate genes near the CoPv01CDRK/PhgPv01CDRK loci and plant defense genes using quantitative real-time PCR in CDRK cultivar inoculated with races 73 of Colletotrichum lindemuthianum and 63-39 of Pseudocercospora griseola. Gene expression analysis revealed that the Phvul.001G246300 gene exhibited the most elevated levels, showing remarkable 7.8-fold and 8.5-fold increases for ANT and ALS, respectively. The Phvul.001G246300 gene encodes an abscisic acid (ABA) receptor with pyrabactin resistance, PYR1-like (PYL) protein, which plays a central role in the crosstalk between ABA and jasmonic acid responses. Interestingly, our results also showed that the other defense genes were initially activated. These findings provide critical insights into the molecular mechanisms underlying plant defense against these diseases and could contribute to the development of more effective disease management strategies in the future.

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Pediatric drugs knowledge still leaves several gaps to be filled, all the while many biopharmaceutic properties applied to adults do not work in pediatrics. The solubility in many cases is extrapolated to pediatrics; however, sometimes it may not represent the real scenario. In this context, the aim of this study was to assess the possibility of the extrapolation of the solubility data assumed for adults to children aged 2-12 years using lamotrigine (LTG) as a model. LTG showed that its solubility is dependent on the pH of the medium, no precipitate formation was seen, and biomimetic media showed a greater capacity to solubilize it. Based on the dose number (D0 ) in adults, the LTG was soluble in acidic pH media and poorly soluble in neutral to basic. Similar behavior was found in conditions which mimic children aged 10-12 years at a dose of 5 and 15 mg/kg. The D0 for 5-year-old children at a dose of 15 mg/kg showed different behaviors between biorelevant and pharmacopeial buffers media. For children aged 2-3 years, LTG appeared to be poorly soluble under both gastric and intestinal conditions. Solubility was dependent on the volume of fluid calculated for each age group, and this may impact the development of better pharmaceutical formulations for this population, better pharmacokinetic predictions in tools as PBPK, and physiologically-based biopharmaceutics modeling, greater accuracy in the justifications for biowaiver, and many other possibilities.

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In this paper, we propose and derive a new regression model for response variables defined on the open unit interval. By reparameterizing the unit generalized half-normal distribution, we get the interpretation of its location parameter as being a quantile of the distribution. In addition, we can evaluate effects of the explanatory variables in the conditional quantiles of the response variable as an alternative to the Kumaraswamy quantile regression model. The suitability of our proposal is demonstrated with two simulated examples and two real applications. For such data sets, the obtained fits of the proposed regression model are compared with that provided by a Kumaraswamy regression model.

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This study evaluated routine laboratory biomarkers (RLB) to predict the infectious bacterial group, Gram-positive (GP) or Gram-negative (GN) associated with bloodstream infection (BSI) before the result of blood culture (BC). A total of 13,574 BC of 6787 patients (217 BSI-GP and 238 BSI-GN) and 68 different RLB from these were analyzed. The logistic regression model was built considering BSI-GP or BSI-GN as response variable and RLB as covariates. After four filters applied total of 320 patients and 16 RLB remained in the Complete-Model-CM, and 4 RLB in the Reduced-Model-RM (RLB p > 0.05 excluded). In the RM, only platelets, creatinine, mean corpuscular hemoglobin and erythrocytes were used. The reproductivity of both models were applied to a test bank of 2019. The new model presented values to predict BSI-GN of the area under the curve (AUC) of 0.72 and 0.69 for CM and RM, respectively; with sensitivity of 0.62 and 0.61 (CM and RM) and specificity of 0.67 for both. These data confirm the discriminatory capacity of the new models for BSI-GN (p = 0.64). AUC of 0.69 using only 4 RLB, associated with the patient's clinical data could be useful for better targeted antimicrobial therapy in BSI.

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Quantile regression allows us to estimate the relationship between covariates and any quantile of the response variable rather than the mean. Recently, several statistical distributions have been considered for quantile modeling. The objective of this study is to provide a new computational package, two biomedical applications, one of them with COVID-19 data, and an up-to-date overview of parametric quantile regression. A fully parametric quantile regression is formulated by first parameterizing the baseline distribution in terms of a quantile. Then, we introduce a regression-based functional form through a link function. The density, distribution, and quantile functions, as well as the main properties of each distribution, are presented. We consider 18 distributions related to normal and non-normal settings for quantile modeling of continuous responses on the unit interval, four distributions for continuous response, and one distribution for discrete response. We implement an R package that includes estimation and model checking, density, distribution, and quantile functions, as well as random number generators, for distributions using quantile regression in both location and shape parameters. In summary, a number of studies have recently appeared applying parametric quantile regression as an alternative to the distribution-free quantile regression proposed in the literature. We have reviewed a wide body of parametric quantile regression models, developed an R package which allows us, in a simple way, to fit a variety of distributions, and applied these models to two examples with biomedical real-world data from Brazil and COVID-19 data from US for illustrative purposes. Parametric and non-parametric quantile regressions are compared with these two data sets.

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The emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to clonal lineages I and III. To evaluate the inhibition of in vitro drug resistance, we investigate the MSW-derived pharmacodynamic indices associated with resistance to polymyxin B administrated regimens as monotherapy and combination therapy, such as the percentage of each dosage interval that free plasma concentration was within the MSW (%TMSW) and the percentage of each dosage interval that free plasma concentration exceeded the mutant prevention concentration (%T>MPC). The MSW of polymyxin B varied between 1 and 16 µg/mL for polymyxin B-susceptible strains. The triple combination of polymyxin B with meropenem and fosfomycin inhibited the polymyxin B-resistant subpopulation in meropenem-resistant isolates and polymyxin B plus meropenem as a double combination sufficiently inhibited meropenem-intermediate, and susceptible strains. T>MPC 90% was reached for polymyxin B in these combinations, while %TMSW was 0 against all strains. TMSW for meropenem and fosfomycin were also reduced. Effective antimicrobial combinations significantly reduced MSW. The MSW-derived pharmacodynamic indices can be used for the selection of effective combination regimen to combat the polymyxin B-resistant strain.

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Modal regression is an alternative approach for investigating the relationship between the most likely response and covariates and can hence reveal important structure missed by usual regression methods. This paper provides a collection of parametric mode regression models for bounded response variable by considering some recently introduced probability distributions with bounded support along with the well-established Beta and Kumaraswamy distribution. The main properties of the distributions are highlighted and compared. An empirical comparison between the considered modal regression is demonstrated through the analysis of three data sets from health and social science. For reproducible research, the proposed models are freely available to users as an R package unitModalReg.

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Over the last decades, the challenges in applied regression have been changing considerably, and full probabilistic modeling rather than predicting just means is crucial in many applications. Motivated by two applications where the response variable is observed on the unit-interval and inflated at zero or one, we propose a parametric quantile regression considering the unit-Weibull distribution. In particular, we are interested in quantifying the influence of covariates on the quantiles of the response variable. The maximum likelihood method is used for parameters estimation. Monte Carlo simulations reveal that the maximum likelihood estimators are nearly unbiased and consistent. Also, we define a residual analysis to assess the goodness of fit.

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AIMS: To compare the pharmacokinetics of amoxicillin (AMX) in obese and nonobese subjects, given as single dose 875-mg tablets. METHODS: A prospective, single-centre, open-label, clinical study was carried out involving 10 nonobese and 20 obese subjects given a dose of an AMX 875-mg tablet. Serial blood samples were collected between 0 and 8 hours after administration of AMX and plasma levels were quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters (PK) were calculated by noncompartmental analysis and means of the 2 groups were compared using Student t-test. Analysis of correlation between covariates and PK was performed using Pearson's correlation coefficient. RESULTS: Ten nonobese subjects (mean age 30.6 ± 7.12 y; body mass index 21.56 ± 1.95 kg/m2 ) and 20 obese subjects (mean age 34.47 ± 7.03 y; body mass index 33.17 ± 2.38 kg/m2 ) participated in the study. Both maximum concentration (Cmax ; 12.12 ± 4.06 vs. 9.66 ± 2.93 mg/L) and area under the curve (AUC)0-inf (34.18 ± 12.94 mg.h/L vs. 26.88 ± 9.24 mg.h/L) were slightly higher in nonobese than in obese subjects, respectively, but differences were not significant. The volume of distribution (V/F) parameter was statistically significantly higher in obese compared to nonobese patients (44.20 ± 17.85 L vs. 27.57 ± 12.96 L). Statistically significant correlations were observed for several weight metrics vs. AUC, Cmax , V/F and clearance, and for creatinine clearance vs. AUC, Cmax and clearance. CONCLUSION: In obese subjects, the main altered PK was V/F as a consequence of greater body weight. This may result in antibiotic treatment failure if standard therapeutic regimens are administered.

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This study was performed to evaluate the effects of supplementation of lactating Nelore cows with calcium salts of long-chain fatty acids (Ca-LCFA) of soybean oil on in vitro oocytes competency, cleavage rate, embryo production rate, pregnancy rate, and sex ratio of transferred embryos. Fifteen multiparous Nelore cows grazed on a Tifton 85 pasture were allotted to two treatments: (1) supplement without fat inclusion (CONT, n = 6) and (2) supplement containing 47.2 g Ca-LCFA /kg (to provide an intake of 0.2 kg Ca-LCFA/day) based on dry matter (n = 9). Animals were subjected to 2.53 ± 1.35 rounds of consecutive ovum pick up at intervals of 27.65 ± 21.72 days. Oocytes were morphologically evaluated, selected, maturated, fertilized, and cultivated for embryo production in vitro and then transferred into recipients who had previously undergone an embryo transfer protocol at a fixed time. The number of aspirated oocytes, the proportion of viable oocytes, cleavage rate, embryo percentage, pregnancy rate, and sex ratio were not affected when Nelore cows were supplemented with Ca-LCFA of soybean oil compared with non-supplemented Nelore cows. In conclusion, our results suggest that feeding a supplement containing 47.2 g Ca-LCFA/kg (to provide an intake of 0.2 kg Ca-LCFA/day) to Nelore cows does not affect in vitro embryo production in lactating Nelore cows. However, further studies...(AU)

Este estudo foi realizado para avaliar os efeitos da suplementação de vacas Nelores em lactação com sais de cálcio de ácidos graxos de cadeia longa (Ca-SCACL) feitos com óleo de soja sobre a competência in vitro de oócitos, taxa de clivagem, taxa de produção de embriões, taxa de prenhez e proporção de sexo de embriões transferidos. Foram utilizadas 15 vacas Nelore (lactantes, multíparas e mantidas em pastagem de Tifton 85) distribuídas em dois tratamentos: (1) suplemento sem inclusão de lipídios (CONT, n = 6) e (2) suplemento contendo 47,2 g Ca-SCACL/kg (para proporcionar uma ingestão de 0,2 kg Ca-SCACL/ dia) com base na matéria seca (n = 9). Os animais foram submetidos a 2,53 ± 1,35 rodadas consecutivas de aspiração folicular a intervalos de 27,65 ± 21,72 dias. Os oócitos foram avaliados morfologicamente, selecionados, maturados, fertilizados e cultivados para produção de embriões in vitro. Em seguida, os embriões foram transferidos para receptoras previamente submetidas a um protocolo de transferência de embriões em tempo fixo. O número de oócitos aspirados, a proporção de oócitos viáveis, a taxa de clivagem, a porcentagem de embriões, a taxa de prenhez e a proporção de sexo de embriões não foram afetados quando as vacas Nelore foram suplementadas com Ca-SCACL de óleo de soja em comparação com as vacas Nelore não suplementadas. Em conclusão, nossos resultados sugerem que suplemento contendo 47,2 g de Ca-SCACL/kg (para fornecer uma ingestão de 0,2 kg de Ca-SCACL) não afeta a produção in vitro de embriões de vacas Nelore em lactação. No entanto, novos estudos utilizando doses mais altas de gordura na dieta poderiam ser úteis para determinar o seu potencial sobre produção embrionária in vitro.(AU)

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