Search Results (60)

When breastfeeding is not possible, infant formulas may be used instead of human milk. However, harmful advanced glycation end-products (AGEs) may be formed during thermal processing of infant formulas. The exposure to AGEs at such an early age can lead to chronic diseases in the future. Therefore, the aim of this study was to develop a sensitive method to determine the content of AGEs in infant formulas. Twenty commercial infant formulas (initial and follow-on) in liquid and powder form were investigated using liquid chromatography with tandem mass spectrometry (LC-MS/MS) with a multistep sample pretreatment procedure. Five selected glycation products were analyzed: N^ε-carboxyethyllysine (CEL), N^ε-carboxymethyllysine (CML), furosine, glyoxal lysine dimer (GOLD), and methylglyoxal lysine dimer (MOLD). The mean contents of the tested glycation products did not differ significantly between the initial and follow-on formulas. No significant differences were found in the concentrations of the analyzed compounds from different manufacturers. However, the liquid formulas contained significantly more CML. The estimated dietary exposure to the tested compounds was in the range of 42.5–92.6 μg/day, except for furosine (almost 2 mg/day). The developed method enabled the determination of selected AGEs in complex matrices such as infant formulas. Consumption of liquid infant formulas can result in higher exposure to some AGEs. Full article

Background/Objectives: Patients with chronic myeloid leukemia (CML) have a long life expectancy due to modern treatment. However, treatment may have adverse effects that hamper work ability. Methods: Patients aged 25–60 years diagnosed in 2002–2020 were included in this nationwide matched cohort study examining work ability from diagnosis (index date), including the need for permanent disability compensation (flexible job or disability pension). Each patient was matched 1:5 on sex, birth year, and level of comorbidity with citizens from the general Danish population without CML. The risks of requiring flexible job and disability pension were calculated by cause-specific hazard ratios (HRs) using Cox proportional hazards regression, and the Aalen–Johansen estimator was used to determine cumulative risks. Results: A total of 489 patients with CML and 2445 matched comparators were included. The median age was 46 years, and males comprised 59.5% of the cohort. Matched comparators were more likely to work at index date and 1, 3, 5, and 10 years after the index date (p < 0.001). The HRs of requiring both flexible job (HR 8.7 (95% confidence interval (CI): 6.1;12.2, p < 0.001)) and disability pension (HR 3.7 (95% CI: 2.8;4.9, p < 0.001)) were higher among patients diagnosed with CML compared to matched comparators. The cumulative risk of requiring flexible job and disability pension also increased in patients with CML compared to matched comparators (p < 0.001). Conclusions: Patients with CML have a reduced work ability compared to the general population. More research is needed to determine the cause of their loss of ability to work. Full article

Missense mutations in the BCR::ABL1 kinase domain are found in approximately 12–80% of patients with chronic myeloid leukemia (CML). Clinically significant mutations include T315I, M244V, Y253H/F, E255K/V, V299L, and F359V. The aim of this study was to create a diagnostic system for rapid and inexpensive detection of the above mutations. We used genomic DNA and RNA from peripheral blood and bone marrow cells of 57 patients with a Ph-positive CML diagnosis established in the chronic phase. We have developed a method to detect mutations in the BCR::ABL1 gene based on allele-specific real-time polymerase chain reaction (AS-PCR). In parallel, we analyzed the RNA sequence of the protein kinase domain of the same samples by next-generation sequencing (NGS) covering the points of putative mutations. In this work, we compared the results obtained by both methods for mutation detection and variant allele frequency (VAF) estimation of mutated vs. normal alleles. The sensitivity and specificity of our diagnostic system were also evaluated. It was found that AS-PCR gives reliable results at VAF up to 0.01%. AS-PCR has high sensitivity and may serve as an alternative for the more time-consuming NGS in some cases, as well as for monitoring CML treatment and for analyzing archival material. Full article

Background: Renal adverse drug reactions (ADRs) associated with tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) are relatively rare, and there is currently no standardized protocol for their management. Therefore, this study aimed to summarize renal ADRs related to TKIs use in CML and propose an evidence-based approach to monitor and manage these ADRs. Methods: A systematic literature review was performed to identify renal ADRs associated with TKIs in CML. Two authors screened the search results and extracted data from 37 eligible studies. These findings were then used to develop a scheme for clinicians to monitor and manage these ADRs. Results: Overall, imatinib seemed to be significantly linked to renal adverse events compared to other TKIs, and switching to dasatinib or nilotinib significantly improved renal function. Similar events were reported with bosutinib, although they were not statistically significant. However, most of the renal events reported on dasatinib were described as nephrotic syndrome that resolved with switching to imatinib. Few cases were reported with nilotinib that described tumor lysis syndrome (TLS)-related kidney injury. Conclusions: Recommendations include monitoring for progressive decline in the estimated glomerular filtration rate with imatinib, nephrotic syndrome with dasatinib, and TLS with nilotinib. Additionally, holding the offending TKI and managing renal ADRs according to local guidelines were adopted more frequently than reducing the TKI dose. Full article

The brown wheat mite, Petrobia tritici, poses a significant threat to wheat fields. While fertilizers can increase crop productivity, imbalanced application may exacerbate plant susceptibility to pests. This study aimed to evaluate the impact of various NPK fertilization programs on P. tritici infestations over two consecutive cropping seasons. The results revealed significant differences in mite infestation among the treatment groups (p < 0.001). The lowest populations (1.1 and 3.0 mites/leaf) were observed in the treatments sprayed with phosphoric acid (at 0.75 and 1.00 cm/L), where the infestation appeared approximately 120 days after sowing; in contrast, it appeared early at 75 days in the other treatments. Conversely, treatments lacking potassium fertilizer presented the greatest degree of mite injury levels (49.5–57.7 mites/leaf). Although these treatments provided moderate leaf nutrition and crop yield, the highest nutritional content and total yield (10.49 and 9.71 1 t/ha for the two years) were observed in the treatment that received 224:70:100 kg fad⁻¹ commercial fertilizers (=178:25:114 kg ha⁻¹ NPK units) as soil fertilization, which was followed by the treatment with a foliar application of phosphoric acid (1.00 cm/L) with a total yield of 9.34 and 8.53 1 t/ha for the two years. In this treatment, the P. tritici density was moderately high at 9.40 and 6.32 mites/leaf over the two years, respectively. The consistency of P. tritici density and total yield ranking across both years indicated reliable estimates of the impact of fertilization. This study suggests that potassium sulfate application is crucial for reducing P. tritici density and that foliar phosphoric acid application instead of soil application reduces the number of P. tritici and delays its occurrence. Full article

Current therapy in chronic myeloid leukemia (CML) has improved patient life expectancy close to that of healthy individuals. However, molecular alterations other than BCR::ABL1 fusion gene in CML are barely known. MicroRNAs are important regulators of gene expression, and variants in some of the components of microRNA biosynthesis pathways have been associated with genetic susceptibility to different types of cancer. Thus, the aim of this study was to evaluate the association of variants located in genes involved in the biogenesis of microRNAs with susceptibility to CML. Fifteen variants in eight genes involved in the biogenesis of miRNAs were genotyped in 296 individuals with CML and 485 healthy participants using TaqMan probes. The association of gene variants with CML and clinical variables was evaluated by a Chi-square test, and odds ratios and 95% confidence intervals were estimated by logistic regression. The variant rs13078 in DICER1 was significantly higher among CML individuals than in healthy participants. In addition, the variants rs7813 and rs2740349 were significantly associated with worse prognosis, according to their Hasford scores, whereas the rs2740349 variant was also associated with a later age at diagnosis. These findings suggest that variants in components of the microRNA biogenesis pathway could be involved in CML genetic risk. Full article

This study aims to evaluate in detail the environmental impacts of the turbines used for electricity generation by wind energy, from a life cycle perspective. For this purpose, a comprehensive literature review is conducted and the life cycle environmental impacts of two sizes of wind turbines, namely 3.6 and 4.8 MW, in Turkey are analyzed. Sustainability studies, especially life cycle assessment (LCA) findings, yield healthy results only if the data used are site-specific. The system has been modeled using GaBi software and the Ecoinvent database. The functional unit is defined as 1 kWh of generated electricity. The impacts have been estimated using the CML 2 Baseline 2001 method. The 4.8 MW turbine has lower environmental impacts than the other turbine. The construction of wind turbines has the greatest share of the environmental impacts of all the options considered. Recycling materials at the end of plant life can reduce unwanted environmental impacts by up to 49%. Similar studies based on site-specific data will help to inform electricity producers and policymakers about wind energy’s current impacts and environmental hotspots. Conducting analogous studies is critical to reducing the environmental impacts of wind energy, which will play an important part in the future of the energy sector. Full article

Background: ABL1 tyrosine kinase inhibitor discontinuation securely became among the therapeutic goal for chronic myeloid leukemia chronic phase patients (CML-CP). To establish successful prognostic factors for treatment-free remission (TFR), it is necessary to diagnose the patients with high-risk molecular relapse, however, a biomarker for the achievement of TFR has not been completely elucidated. Recent investigations have determined that neutrophils function crucially in cancer immunology. Patients and Methods: The research was a multicenter retrospective observational study to examine the correlation between TFR and neutrophil counts before TKI discontinuation. The investigation included patients having Philadelphia chromosome-positive CML-CP who attempted the discontinuation of TKIs after a durable deep molecular response between January 2012 and July 2021 at four institutions in Japan. Results: 118 CML-CP patients in total discontinued TKIs and an estimated 36-month TFR rate was 65.1%. 52 patients received second-generation TKIs as frontline. Higher neutrophil count (>3210/μL) at TKIs discontinuation was determined as an independent prognostic variable for TFR in patients who received second-generation TKIs as frontline [(HR, 0.235 (95%, confidence interval (CI) 0.078–0.711); p = 0.010]. Conclusions: The neutrophil-mediated immunomodulation can be a significant component for the effective achievement of TFR in CML supported by our clinical observation. Full article

Tyrosine kinase inhibitor (TKI) drugs have significantly improved chronic myeloid leukemia (CML) outcomes. Neopeptides from CML cells may induce specific immune responses, which are crucial for deep molecular (DMR) and treatment-free remission (TFR). In this study of Ethiopian patients with CML (n = 162), the HLA alleles and single-nucleotide polymorphisms of five cytokines revealed significant associations with clinical outcomes. Clinically unfavorable outcomes correlated with HLA alleles A*03:01/02, A*23:17:01, B*57:01/02/03, and HLA-DRB4*01:01 (p-value = 0.0347, p-value = 0.0285, p-value = 0.037, and p-value = 0.0127, respectively), while HLA-DRB4*01:03:01 was associated with favorable outcomes (p-value = 0.0058). After assigning values for the ‘low’, ‘intermediate’, and ‘high’ gene expression of the SNPs’ respective cytokine genes, Kaplan–Meier estimates for relapse-free survival, adjusted for age, treatment duration, and relapse risk among patients after the administration of TKIs, indicated that a gene expression ratio above the overall median of TNF-α, IL-6, and the combination of TGF-β1/IL-10, IFNγ, and IL-6/IL-10 TGF-β1 was correlated with a higher likelihood of treatment failure ((RR: 3.01; 95% CI: 1.1–8.3; p-value = 0.0261) and (RR: 2.4; 95% CI: 1.1–5.2; p-value = 0.022), respectively). Multi-SNPs, surpassing single-SNPs, and HLA allele polymorphisms showed promise in predicting outcomes of patients with CML during TKI treatment, prompting further exploration into their potential utility. Full article

While overdispersion is a common phenomenon in univariate count time series data, its exploration within bivariate contexts remains limited. To fill this gap, we propose a bivariate integer-valued autoregressive model. The model leverages a modified binomial thinning operator with a dispersion parameter $\rho$ and integrates random coefficients. This approach combines characteristics from both binomial and negative binomial thinning operators, thereby offering a flexible framework capable of generating counting series exhibiting equidispersion, overdispersion, or underdispersion. Notably, our model includes two distinct classes of first-order bivariate geometric integer-valued autoregressive models: one class employs binomial thinning (BVGINAR(1)), and the other adopts negative binomial thinning (BVNGINAR(1)). We establish the stationarity and ergodicity of the model and estimate its parameters using a combination of the Yule–Walker (YW) and conditional maximum likelihood (CML) methods. Furthermore, Monte Carlo simulation experiments are conducted to evaluate the finite sample performances of the proposed estimators across various parameter configurations, and the Anderson-Darling (AD) test is employed to assess the asymptotic normality of the estimators under large sample sizes. Ultimately, we highlight the practical applicability of the examined model by analyzing two real-world datasets on crime counts in New South Wales (NSW) and comparing its performance with other popular overdispersed BINAR(1) models. Full article

A comprehensive study on maize flowering traits, focusing on the regulation of flowering time and the elucidation of molecular mechanisms underlying the genes controlling flowering, holds the potential to significantly enhance our understanding of the associated regulatory gene network. In this study, three tropical maize inbreds, CML384, CML171, and CML444, were used, along with a temperate maize variety, Shen137, as parental lines to cross with Ye107. The resulting F1s underwent seven consecutive generations of self-pollination through the single-seed descent (SSD) method to develop a multiparent population. To investigate the regulation of maize flowering time-related traits and to identify loci and candidate genes, a genome-wide association study (GWAS) was conducted. GWAS analysis identified 556 SNPs and 12 candidate genes that were significantly associated with flowering time-related traits. Additionally, an analysis of the effect of the estimated breeding values of the subpopulations on flowering time was conducted to further validate the findings of the present study. Collectively, this study offers valuable insights into novel candidate genes, contributing to an improved understanding of maize flowering time-related traits. This information holds practical significance for future maize breeding programs aimed at developing high-yielding hybrids. Full article

Fiber-reinforced cementitious matrix (FRCM) composites have been largely used to strengthen existing concrete and masonry structures in the last decade. To design FRCM-strengthened members, the provisions of the Italian CNR-DT 215 (2018) or the American ACI 549.4R and 6R (2020) guidelines can be adopted. According to the former, the FRCM effective strain, i.e., the composite strain associated with the loss of composite action, can be obtained by combining the results of direct shear tests on FRCM–substrate joints and of tensile tests on the bare reinforcing textile. According to the latter, the effective strain can be obtained by testing FRCM coupons in tension, using the so-called clevis-grip test set-up. However, the complex bond behavior of the FRCM cannot be fully captured by considering only the effective strain. Thus, a cohesive approach has been used to describe the stress transfer between the composite and the substrate and cohesive material laws (CMLs) with different shapes have been proposed. The determination of the CML associated with a specific FRCM–substrate joint is fundamental to capture the behavior of the FRCM-strengthened member and should be determined based on the results of experimental bond tests. In this paper, a procedure previously proposed by the authors to calibrate the CML from the load response obtained by direct shear tests of FRCM–substrate joints is applied to different FRCM composites. Namely, carbon, AR glass, and PBO FRCMs are considered. The results obtained prove that the procedure allows to estimate the CML and to associate the idealized load response of a specific type of FRCM to the corresponding CML. The estimated CML can be used to determine the onset of debonding in FRCM–substrate joints, the crack number and spacing in FRCM coupons, and the locations where debonding occurs in FRCM-strengthened members. Full article

There is little data on directly measured carboxymethyl lysine (CML) content in Indonesian foods. This study aimed to generate a database of CML values in foods commonly consumed in West Java and West Sumatra. The results were to be used to update our previous estimated CML values. CML values in food samples were measured using high-pressure liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Food protein content was analyzed by Kjeldahl’s method or inferred from the nutrition facts’ label. A total of 210 food samples were examined, with the food groups of meat and poultry (1.06 mg CML/100 g edible food), and starchy foods (0.21 mg/100 g edible food) having the highest and lowest mean CML levels, respectively. We found that the foods with the top three highest CML content were fried starch dough (cimol), fried fish crackers, and chicken gulai. The mean of the estimated values (0.80 mg CML/100 g edible food) was higher than the directly measured values (0.66 mg CML/100 g edible food), [p < 0.035]. Conclusion: This database provides information on CML values in Indonesian foods, and can be further used to make a guide policy for the selection of foods to reduce non-communicable diseases. Further measurements are needed on Indonesian dishes to complete the database. Full article

Background: Second- and third-generation tyrosine kinase inhibitors (TKIs) are now available to treat chronic-phase chronic myeloid leukemia (CP-CML) in the first and second line. However, vascular adverse events (VAEs) have been reported for patients with CML treated with some TKIs. Methods: We retrospectively evaluated the cumulative incidence (CI) and cardiovascular risk for 210 patients included in the Canarian Registry of CML. Result: With a mean follow up of 6 years, 19/210 (9.1%) patients developed VAEs, all of whom presented at least one cardiovascular risk factor at diagnosis. The mean time to VAE presentation was 54 months from the start of TKI treatment. We found a statistically significant difference between the CI for nilotinib-naïve vs. nilotinib-treated patients (p = 0.005), between dasatinib-naïve and dasatinib-treated patients (p = 0.039), and for patients who received three lines of treatment with first-line imatinib vs. first-line imatinib (p < 0.001). From the multivariable logistic regression analyses, the Framingham risk score (FRS) and patients with three lines of TKI with first-line imatinib were the only variables with statistically significant hazard ratios for VAE development. Significant increases in HDL-C and total cholesterol may also be predictive for VAE. Conclusions: In conclusion, it is important to estimate the cardiovascular risk at the diagnosis of CML as it can help determine whether a patient is likely to develop a VAE during TKI treatment. Full article

In this paper, a time-varying first-order mixture integer-valued threshold autoregressive process driven by explanatory variables is introduced. The basic probabilistic and statistical properties of this model are studied in depth. We proceed to derive estimators using the conditional least squares (CLS) and conditional maximum likelihood (CML) methods, while also establishing the asymptotic properties of the CLS estimator. Furthermore, we employed the CLS and CML score functions to infer the threshold parameter. Additionally, three test statistics to detect the existence of the piecewise structure and explanatory variables were utilized. To support our findings, we conducted simulation studies and applied our model to two applications concerning the daily stock trading volumes of VOW. Full article