Simultaneous Evaluation Research Articles

High-resolution melting assay for rapid, simultaneous detection of JAK2, MPL and CALR variants

AimsIdentification of recurrent genetic alterations in JAK2, MPL and CALR remains crucial in the diagnosis of Philadelphia-negative myeloproliferative neoplasms (MPNs). Current laboratory testing algorithms may entail batching and/or sequential testing,...

Rational Design of a Portable Chemometric-Assisted Voltammetric Sensor Based on Ion-Imprinted Polymeric Film for Co(II) Determination in Water.

Herein, chemometric-assisted synthesis of electrochemical sensors based on electropolymerised ion-imprinted polymeric (e-IIP) films was explored. Co(II)-IIPs sensors were prepared by performing electropolymerisation procedures of polymerisation mixtures comprising varying concentrations of an electroactive o-aminophenol (o-AP) monomer and Co(II) ions, respectively, according to the Taguchi L9 experimental design, exploiting the simultaneous evaluation of other controlled parameters during electrosynthesis. Each e-IIP developed from Taguchi runs was compared with the respective non-imprinted polymer (NIP) films and fitted according to Langmuir-Freudlich isotherms. Distinctive patterns of low and high-affinity films were screened based on the qualities and properties of the developed IIPs in terms of binding kinetics (KD), imprinting factor, and the heterogeneity index of produced cavities. These results can provide a generic protocol for chemometric-assisted synthesis of e-IIPs based on poly-o-AP, providing highly stable, reproducible, and high-affinity imprinted polymeric films for monitoring purposes.

MLPA in the initial genetic screening of patients with acute myeloid leukemia.

This study aimed to assess the effectiveness of multiplex ligase-dependent probe amplification (MLPA) in the initial genetic screening of patients with acute myeloid leukemia (AML) since current risk stratification and clinical management depend on molecular-genetic markers. We performed a prospective case-control study on newly diagnosed patients from the Clinical hematology clinic of UMHAT "St. Marina", Varna, for the period 02.2022 - 02.2023. MLPA - a semiquantitative PCR-based method, was implemented with probes for 40 AML/myelodysplastic syndrome-typical genetic changes. We compared these findings with a parallelly carried out cytogenetic analysis, part of the routine diagnostic process. We assessed 61 patients - 29 females and 32 males, median age of 61 years for females and 65 for males (min-max 20-89). 34 (56%) of all showed pathological results, while the rest 27 (44%) did not. Of the 34, 22 (65%) had a single gene variant in genes NPM1, DNMT3A, FLT3, and IDH2, isolated or in combination. 18 (53%) of the same 34 also had copy number aberration (CNA) in chromosomes 4, 5, 6, 7, 11, 14, 17, and 21. The latter were either isolated or in combination with other findings. 8 of the 18 cases also underwent cytogenetic analysis, with concordance between the two methods in 4. MLPA is an informative method for initial genetic assessment in addition to cytogenetic analysis. Still, more patients are needed to draw finite conclusions on its eligibility for routine use. Given the significant percentage of normal results - 44%, simultaneous evaluation of more genetic markers, included in current guidelines, is reasonable.

Specific fractionation of ginsenosides based on activated carbon fibers and online fast screening of ginseng extract by mass spectrometry

Ginseng is beneficial in the prevention of many diseases and provides benefits for proper growth and development owing to the presence of various useful bioactive substances of diverse chemical heterogeneity (e.g., triterpenoid saponins, polysaccharides, volatile oils, and amino acids). As a result, understanding the therapeutic advantages of ginseng requires an in-depth compositional evaluation employing a simple and rapid analytical technique.In this work, three types of surface-activated carbon fibers (ACFs) were prepared by gas-phase oxidation, strong acid treatment, and Plasma treatment to obtain CO2-ACFs, acidified-ACFs, and plasma-ACFs, respectively. Three prepared ACFs were compared in terms of their physicochemical characterization (i.e., surface roughness and functional groups). A separation system was built using a column with modified ACFs, followed by mass spectrometry detection to investigate and determine substances of different polarities. Among the three columns, CO2-ACFs showed the optimum separation effect. 13 strong polar compounds (12 amino acids and1 oligosaccharide) and 15 lesser polar compounds (ginsenosides) were separated and identified successfully within 4 min in the ginseng sample. The data obtained by CO2-ACFs-TOF-MS/MS and UHPLC-TOF-MS/MS were compared. Our approach was found to be faster (4 min vs. 36 min) and greener, requiring much less solvent (1 mL vs. 10.8 mL), and power (0.06 vs. 0.6 kWh). The developed methodology can provide a faster, eco-friendly, and more reliable tool for the high-throughput screening of complex natural matrices and the simultaneous evaluation of several compounds in diverse samples.

Simultaneous evaluation of brain metastasis and thoracic cancer using semiconductor 11C-methionine PET/CT imaging.

To investigate the potential of whole-body digital 11C-methionine (MET) PET/CT imaging for simultaneous evaluation of thoracic cancer patients suspected of local recurrence (LR) after stereotactic radiosurgery (SRS) for brain metastasis. A total of 45 lung or breast cancer patients suspected of LR after SRS were investigated using brain and whole-body MET-PET/CT scans. We compared the tumor-to-normal ratio (TNR) and maximum standardized uptake values (SUVmax) between patients with LR and radiation necrosis (RN) and performed receiver operating characteristic (ROC) analyses. We also investigated associations among extracranial recurrence, intracranial recurrence, primary site, and initial treatment type. A total of 44 LR and 14 RN lesions were analyzed. In the ROC analyses for differentiating LR from RN, TNR showed higher area under the curve (AUC) (0.82) than SUVmax (0.79), and the cutoff TNR value (2.12) was higher than current cutoff values of conventional PET systems. The whole-body scans detected extracranial recurrences in 31.1% of the patients. Recurrence rates were not significantly correlated with existence of intracranial recurrence or primary site, but patients who underwent non-surgical treatment (consisting of stage III/ IV patients according to the Union for International Cancer Control TNM classification or small-cell lung cancer patients) showed significantly higher recurrence than the surgically treated patients (68.8% vs. 10.3%, p = 0.0001). In digital MET-PET/CT imaging, TNR was a more useful parameter to differentiate LR from RN than SUVmax, and the cutoff value was higher than those with conventional PET systems. Additional whole-body scans could detect extracranial recurrence and would be especially useful for advanced thoracic cancer patients who underwent non-surgical treatment.

Simultaneous assessment of stress hyperglycemia ratio and glycemic variability to predict mortality in patients with coronary artery disease: a retrospective cohort study from the MIMIC-IV database

BackgroundStress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU).MethodsPatients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses.ResultsA total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494–26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175–10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542–11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224–3.311) was observed in patients with high SHR levels but low GV.ConclusionsThe simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.

Correlation of salivary cytokine IL-17A and 1,25 dihydroxycholecalciferol in patients undergoing orthodontic treatment.

The management of malocclusion has developed greatly in terms of treatment simulation and biomechanics, but treatment duration has been a great concern to the clinician as well as the patient. 1-25dihydroxycholecalciferol (biologically active form of Vitamin D) stimulates both osteoclasts and osteoblasts and was found to be the most significant in Orthodontic Tooth Movement acceleration. Inflammatory cytokines like IL-17A also play an important role in osteoclastogenesis and can enhance the rate of Orthodontic Tooth Movement.To perform a simultaneous evaluation of pro-inflammatory salivary cytokine IL-17A and salivary 1-25dihydroxycholecalciferol and to correlate their role on orthodontic tooth movement.A prospective cohort study was conducted among n = 97 patients. Saliva samples were collected from the patients at three phases of the orthodontic treatment, centrifuged and stored at 4℃ for evaluation of salivary 1-25dihydroxycholecalciferol levels and Pro-inflammatory cytokine IL-17A using ELISA.The mean salivary 1-25dihydoxycholecalciferol levels were 41.250ng/ml, 33.246ng/ml and 35.043ng/ml during the initial phase, lag phase and post lag phase of orthodontic treatment. The mean pro-inflammatory cytokine IL-17 A levels were 107.79pg/ml, 102.98pg/ml and 66.156pg/ml during the initial phase, lag phase and post lag phase of orthodontic treatment. There was a correlation between the salivary 1-25dihydroxycholecalciferol level and salivary cytokine IL-17A levels during the various phases of orthodontic treatment using Spearman's correlation rho test and linear regression analysis. There was no significant difference (p > 0.05) between 1-25dihydroxycholecalciferol levels and gender during the various phases (initial phase, lag phase and post lag phase) of Orthodontic treatment.There was a negative correlation between salivary 1-25dihydroxycholecalciferol level and salivary cytokine IL-17A levels during the various phases of orthodontic treatment. The level of 1-25dihydroxycholecalciferol and salivary cytokine IL-17A have been quantified during the various phases of Orthodontic treatment and this can be used clinically for the supplementation of Vitamin D in patients with low vitamin D levels and can enhance the treatment duration for the patient with less damaging effects to the surrounding tissues.

First simultaneous evaluation of fission probabilities and neutron-induced cross sections for the Pu fissile isotopes

Surrogate reactions are a powerful tool to access neutron-induced reaction cross sections of short-lived nuclei. However, to infer neutron-induced reaction cross sections from measured deexcitation probabilities requires a consistent and rigorous theoretical framework describing both charged-particle and neutron-induced reactions. This work presents the first practical application of the new approach developed in O. Bouland, Phys. Rev. C 100, 064611 (2019) to Pu fissile isotopes, 237,238,240,242,244Pu*. Average neutron-induced reaction cross sections and deexcitation probabilities measured in surrogate reactions are simultaneously analyzed with an efficient Monte Carlo R-matrix-extended theory algorithm using a unique set of nuclear-structure parameters to describe both observables. Fission probabilities allow one to estimate fission-barrier heights, not otherwise accessible in fissile isotopes. The theoretical framework is here extended to model 'giant' resonance structures observed in the fission probabilities of some nuclides. A careful study of the impact of the uncertainties on nuclear parameters and on the populated compound system angular distribution has been carried out. This study raises questions on the normalization of some fission probabilities measured in the 70's in (t,p) reactions, that could not have been pointed out without the use of the here-presented complex technique. This finding is especially important for the peculiar 240Pu* system. In addition, our study reveals for the 237Pu* compound system a 10 to 30% too high value of the only-performed low-energy neutron-induced fission cross section measurement (Gerasimov et al., JINR-E–3-97-213 (1997)) and, subsequently of the evaluated fission cross section below 50 keV for the 236Pu.

Abstract B032: Comprehensive analysis of clonality, segregation errors, chromosomal instability and heterogeneity in cancer cell lines and cancer samples reveals that cancer evolution is often promoted by highly aberrant cellular divisions

Abstract Chromosomal instability (CIN) is the most common form of genomic instability in cancer. CIN leads to structural and numerical chromosomal aberrations and to heterogeneity of such aberrations inside the same tumor. Together with other forms of genomic and epigenomic instability, CIN underlies the most dangerous feature of cancer cells, namely, ability to evolve, allowing cancer cells to evade immunologic surveillance, to metastasize, to become resistant to drug treatments. Studies of chromosomal instability are significantly impeded by the lack of comprehensive approaches for simultaneous detection of different forms of ongoing chromosomal instability and their outcomes. We developed an approach that allows to analyze the clonal composition and chromosomal heterogeneity in cell lines and cancer samples, as well as rates of different forms of ongoing chromosomal instability in cancer cell lines. At the heart our analysis is a multiplex interphase FISH (miFISH) with seven sequential hybridizations of color probe panels resulting in the assessment of a total of 35 probes per single cell. Each probe panel is designed to include the centromeric probe and probes on the p- and q-arm for a given chromosome that allows for the simultaneous assessment of centromeric probes and gene-specific arm probes. This approach was applied to interphase nuclei, metaphase spreads and bi-nucleated/dividing cancer cells in colorectal and cervical cell lines and cancer samples. miFISH allows for automated acquisition of nuclei and metaphase spreads on a BioView spotcounting system. A gallery provides detailed views for semi-automatic as well as manual analysis of the obtained images. A total of 10000-25000 cell images were collected from each slide. The simultaneous evaluation of our strategically chosen centromeric and gene-specific probes within the same cells allows unprecedented insights in the patterns of distribution of genetic material among cancer cells in cancer cell population, and, especially, in dividing cells. We evaluated clonality, clonal and non-clonal chromosomal heterogeneity, ploidy distributions, and occurrence of endoreplication. Assessment of dividing cells based on equal or unequal distribution of miFISH centromeric and gene-specific signals allowed to estimate and compare the rates and outcomes of different forms of ongoing chromosomal instability such as structural rearrangements and amplifications, loss of chromosomes or chromosomal fragments in micronuclei, non-disjunctions, grossly asymmetrical cell divisions (including multipolar mitoses). Conclusions: Gradual changes in chromosomal/genomic content of cancer cells occur due to structural rearrangements, losses of chromosomes and chromosomal fragments in micronuclei, and by relatively rare single chromosome non-disjunctions. Grossly abnormal cell divisions (massive non-disjunctions and structural rearrangements) is the main source for the high level of chromosomal abnormalities and aneuploidy in evolved cancer cell populations. Citation Format: Anna Roschke. Comprehensive analysis of clonality, segregation errors, chromosomal instability and heterogeneity in cancer cell lines and cancer samples reveals that cancer evolution is often promoted by highly aberrant cellular divisions [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B032.

BioProtIS: Streamlining protein-ligand interaction pipeline for analysis in genomic and transcriptomic exploration

The identification of protein-ligand interactions plays a pivotal role in elucidating biological processes and discovering potential bioproducts. Harnessing the capabilities of computational methods in drug discovery, we introduce an innovative Inverted Virtual Screening (IVS) pipeline. This pipeline Integrated molecular dynamics and docking analyses to ensure that protein structures are not only energetically favorable but also representative of stable conformations. The primary objective of this pipeline is to automate and streamline the analysis of protein-ligand interactions at both genomic and transcriptomic scales. In the contemporary post-genomic era, high-throughput computational screening for bioproducts, biological systems, and therapeutic drugs has become a cornerstone practice. This approach offers the promise of cost-effectiveness, time efficiency, and optimization of laboratory work. Nevertheless, a notable deficiency persists in the availability of efficient pipelines capable of automating the virtual screening process, seamlessly integrating input and output, and leveraging the full potential of open-source tools. To bridge this critical gap, we have developed a versatile pipeline known as BioProtIS. This tool seamlessly integrates a suite of state-of-the-art tools, including Modeller, AlphaFold, Gromacs, FPOCKET, and AutoDock Vina, thus facilitating the streamlined docking of ligands with an expansive repertoire of proteins sourced from genomes and transcriptomes, and substrates. To assess the pipeline's performance, we employed the transcriptomes of Cereus jamacaru (a cactus species) and Aspisoma lineatum (firefly), along with the genome of Homo sapiens. This integration not only improves the accuracy of ligand-protein interactions by minimizing replicability deviations but also optimizes the discovery process by enabling the simultaneous evaluation of multiple substrates. Furthermore, our pipeline accommodates distinct testing scenarios, such as blind docking or site-specific targeting, which are invaluable in applications ranging from drug repositioning to the exploration of new allosteric binding sites and toxicity assessments. BioProtIS has been designed with modularity at its core. This inherent flexibility empowers users to make custom modifications directly within the source code, tailoring the pipeline to their specific research needs. Moreover, it lays the foundation for seamless integration of diverse docking algorithms in future iterations, promising ongoing advancements in the field of computational biology. This pipeline is available for free distribution and can be download at: https://github.com/BBMDO/BioProtIS.

P493 Do antiTNF or Ustekinumab trough levels correlate with joint extraintestinal manifestations activity in Inflammatory bowel disease patients?

Abstract Background Inflammatory spondyloarthritis(SpA) are the most common extraintestinal manifestations (EIM) associated to inflammatory bowel disease (IBD), with a prevalence of 20-50% for axial SpA(axSpA) and 5-20% for peripheral(pSpA). AntiTNF is the optimal therapy in axSpA intolerant or refractory to NSAIDs, also effective in pSpA. An optimal trough level has not been yet established in this clinical setting. Aim, to evaluate the correlation between antiTNF and UST trough levels and joint EIM activity in IBD patients. Methods Prospective, multicenter,cohort study. IBD patients diagnosed with articular EIM under antiTNF or Ustekinumab(UST) for at least 6 months were included. Blood samples were obtained just before administering the drug(trough levels), and a simultaneous evaluation by a rheumatologist and a gastroenterologist, was performed. Definitions: inactive AxSp=ASDAS-CRP&amp;lt;1.3 and BASDAI&amp;lt;2, inactive pSp=arthritis, enthesitis and dactylitis=0, active AxSp=ASDAS-CRP &amp;gt;2.1 and BASDAI&amp;gt;4, active pSp= artritis, entesitis o dactilitis &amp;gt; 0. Aim, to evaluate the correlation between antiTNF and UST trough levels and joint EIM activity in IBD patients. Results A total of 135 patients were included: mean age 51 ± 15, 59 (43.7%)women), 80% CD. 60(44.4%) patients presented axSpA, 50(37%) pSpA and 25(18.5%) mixed. 12(8.9%) had active IBD. Table 1 summarizes the patients' main demographic and clinical characteristics distributed by SpA activity. Fifty-three(39%) were on infliximab (IFX), 61(45.2%), on adalimumab (ADA) and 22 (16.3%) on UST treatment. NSAIDs treatment(12.7% vs 3.1%, p&amp;lt;0.05), higher fecal calprotectin(FC)(486 ± 709 vs 228.2 ± 297, p&amp;lt;0.05), and the prior use of biologics(33.8% vs 17.6%, p&amp;lt;0.05) were more frequent among active vs inactive SpA patients. No differences between IFX(7.05 ± 4.16 vs 5.79± 4.05, p=ns), ADA(7.98 ± 4.20 vs 9.51 ± 6.15 p=ns) and UST levels(3.39 ± 3.47 vs 3.08 ±2.69, p=ns), were found between active and inactive SpA patients, even when were distributed by type of SpA(axSpA/mixed and pSpA). Body mass index(b:-0,29, p=0.01)FC(b:-0,28, p=0.01), and intensified therapy(b:-0,28, p=0.01) were associated to higher IFX levels in the whole SpA cohort. Patients with axSpA or mixed were articular active more frequently than pSpA patients(82% vs 18%, p &amp;lt;0.05). IBD activity was correlated to articular activity only among pSpA patients(2% active IBD in inactive pSpA vs 20% active IBD in active pSpA patients, p=0.03). Conclusion AntiTNF and UST trough levels are not correlated to joint activity in patients with IBD and SpA. In our study more than 80% of patients with active SpA were inactive regarding IBD. Only pSpA patients presented correlation between IBD and articular activities.

Simultaneous evaluation of iris area and subfoveal choroidal thickness in Fuchs uveitis syndrome

Background/aimsTo simultaneously evaluate iris area (IA) and subfoveal choroidal thickness (SFCT) in eyes with Fuchs Uveitis Syndrome (FUS).MethodsWe prospectively recruited a case series of patients with FUS at our institution, simultaneously measuring IA with anterior segment spectral domain optical coherence tomography (SD-OCT) and SFCT with enhanced depth imaging optical coherence tomography (EDI-OCT). Iris images were analyzed by ImageJ software. We tested the differences in intereye IA and SFCT with the healthy eye (HE) using the Wilcoxon test, and clinical interpretation was controlled by intraclass correlation coefficient (ICC) between two masked specialists.ResultsSixteen patients with unilateral FUS were included. Six were female, and the age range was 37 to 67 (median age 48 years, IQR 41–60). ICC of 98.9%, with a lower confidence interval of 97%. Eyes with FUS had a significant thinning of the total iris median area (p < 0.002), restricted to the temporal and nasal areas compared to the HE (p < 0.01 and < 0.001, respectively). SFCT was also significantly thinner compared to the HE (p < 0.0001). A low correlation was found between iris and choroidal thinning in FUS eyes (rs = 0.21; p = 0.4).ConclusionsThis study found reduced iris area and subfoveal choroidal thickness in eyes with FUS compared to the normal fellow eye.

Bromide Ion Impurity-Induced Reaction between Selenium(IV) and Acidic Bromate: Prototype of a Cycle with Autocatalytic Behavior.

The selenium(IV)-bromate reaction in an acidic medium using phosphoric acid/phosphate buffer was investigated by UV-vis spectroscopy monitoring the formation of bromine. In an excess of bromate, the absorbance-time curves measured at 450 nm display a characteristic sigmoidal shape having a fairly long induction period, while in the opposite case, when selenium(IV) species is used in excess, the measured data follow the rise and fall behavior. Depending on the excess of Se(IV) the final bromine-containing product is either an elementary bromine or bromide ion. Simultaneous evaluation of the measured kinetic traces clearly indicated that, surprisingly, no direct reaction takes place between the reactants. Instead of that, a trace amount of bromide ion impurity in the stock bromate solution is sufficient to drive the system via the oxidation of the bromide ion by bromate producing elementary bromine followed by the subsequent selenite-bromine reaction reestablishing the bromide ion to open a new cycle. As a result, the concentration of bromide ions increases in a sigmoidal fashion during the course of the reaction unless enough selenium(IV) species is present; hence, the overall synergetic effect observed is the autocatalytic rise of bromide ions. Therefore, the cycle mentioned above may be considered as a prototype of autocatalytic cycles. This observation prompted us to clarify the explicit difference between an autocatalytic cycle and an autocatalytic reaction.

Digital Twin Framework for Built Environment: A Review of Key Enablers

The emergence of Digital Twin (DT) technology presents unique opportunities for society by facilitating real-time data transfer from the physical environment to its digital counterpart. Although progress has been made in various industry sectors such as aerospace, the Architecture, Engineering, Construction, and Operation (AECO) sector still requires further advancements, like the adoption of these technologies over traditional approaches. The use of these technologies should become standard practice rather than an advanced operation. This paper aims to address the existing gap by presenting a comprehensive framework that integrates technologies and concepts derived from purpose-driven case studies and research studies across different industries. The framework is designed to provide best practices for the AECO sector. Moreover, it aims to underscores the potential of DT for optimization through overseeing and digital management of the built environment across the entire life cycle of facilities, encompassing design, construction, operation, and maintenance. It is based on an extensive literature review and presents a holistic approach to outlining the roles of Building Information Modelling (BIM), Geographic Information Systems (GIS), Internet of Things (IoT), and other key enablers within the DT environment. These digital tools facilitating the simultaneous evaluation of associated benefits, such as resource savings and future prospects, like monitoring project sustainability objectives.

Multivariate generalized mixed-effects models for screening multiple adverse drug reactions in spontaneous reporting systems.

Introduction: For assessing drug safety using spontaneous reporting system databases, quantitative measurements, such as proportional reporting rate (PRR) and reporting odds ratio (ROR), are widely employed to assess the relationship between a drug and a suspected adverse drug reaction (ADR). The databases contain numerous ADRs, and the quantitative measurements need to be calculated by performing the analysis multiple times for each ADR. We proposed a novel, simple, and easy-to-implement method to estimate the PRR and ROR of multiple ADRs in a single analysis using a generalized mixed-effects model for signal detection. Methods: The proposed method simultaneously analyzed the association between any drug and numerous ADRs, as well as estimated the PRR and ROR for a specific combination of drugs and suspected ADRs. Furthermore, the proposed method was applied to detect drug-drug interactions associated with the concurrent use of two or more drugs. Results and discussion: In our simulation studies, the false-positive rate and sensitivity of the proposed method were similar to those of the traditional PRR and ROR. The proposed method detected known ADRs when applied to the Food and Drug Administration Adverse Event Reporting System database. As an important advantage, the proposed method allowed the simultaneous evaluation of several ADRs using multiple drugs.

Bayesian Methods for Information Borrowing in Basket Trials: An Overview.

Basket trials allow simultaneous evaluation of a single therapy across multiple cancer types or subtypes of the same cancer. Since the same treatment is tested across all baskets, it may be desirable to borrow information across them to improve the statistical precision and power in estimating and detecting the treatment effects in different baskets. We review recent developments in Bayesian methods for the design and analysis of basket trials, focusing on the mechanism of information borrowing. We explain the common components of these methods, such as a prior model for the treatment effects that embodies an assumption of exchangeability. We also discuss the distinct features of these methods that lead to different degrees of borrowing. Through simulation studies, we demonstrate the impact of information borrowing on the operating characteristics of these methods and discuss its broader implications for drug development. Examples of basket trials are presented in both phase I and phase II settings.

Framework for metamodel-based design optimization considering product performance and assembly process complexity

This paper proposes a method for simultaneous evaluation of the assembly process complexity together with the performance of the future product. It allows for product design optimization, considering different aspects of the future design at the early stage of the development process. The proposed method, embodied in a fully automated framework, substitutes the traditional sequential development process with a more efficient and rapid combined procedure, which addresses multiple design aspects simultaneously. Design for assembly (DFA) rules, used as quantitative metrics of the ease-of-assembly of the whole product and individual assembly operations, are automatically evaluated together with performance metrics, estimated based on finite element (FE) simulations. The direct solution to this optimization problem might be inefficient or impossible since it requires the recurrent evaluation of computationally expensive discrete and continuous functions with unknown behavior that represent the optimization objectives and constraints. For that reason, the proposed framework employs regression models based on the Gaussian process and artificial neural networks, thus achieving the optimal design of a product as a result of metamodel-based design optimization (MBDO). The suggested approach is demonstrated in the optimization of a gearbox assembly, considering its mechanical performance and assembly process. Comparing the results of the metamodel-based and direct design optimization shows that MBDO allows finding a better solution using a three times smaller computational budget. In addition, analysis of the results obtained using stationary sampling data sets of different sizes highlighted the limitations of the employed sampling procedure.

Implementation and Validation of Explicit Immersed Boundary Method and Lattice Boltzmann Flux Solver in OpenFOAM

In this work, the explicit boundary-condition-enforced immersed boundary method (EIBM) and the lattice Boltzmann flux solver (LBFS) are integrated into OpenFOAM to efficiently solve incompressible flows with complex geometries and moving boundaries. The EIBM applies the explicit technique to greatly improve the computational efficiency of the original boundary-condition-enforced immersed boundary method. In addition, the improved EIBM inherits the accurate interpretation of the no-slip boundary condition and the simple implementation from the original one. The LBFS uses the finite volume method to discretize the recovered macroscopic governing equations from the lattice Boltzmann equation. It enjoys the explicit relationship between the pressure and density, which avoids solving the pressure Poisson equation and thus saves much computational cost. Another attractive feature of the LBFS lies in its simultaneous evaluation of the inviscid and viscous fluxes. OpenFOAM, as an open-source CFD platform, has drawn increasing attention from the CFD community and has been proven to be a powerful tool for various problems. Thus, implementing the EIBM and LBFS into such a popular platform can advance the practical application of these two methods and may provide an effective alternative for complicated incompressible flow problems. The performance of the integrated solver in OpenFOAM is comprehensively assessed by comparing it with the widely used numerical solver in OpenFOAM, namely, the Pressure-Implicit with Splitting of Operators (PISO) algorithm with the IBM. A series of representative test cases with stationary and moving boundaries are simulated. Numerical results confirm that the present method does not have any streamline penetration and achieves the second-order accuracy in space. Therefore, the present method implemented in the open-source platform OpenFOAM may have good potential and can serve as a powerful tool for practical engineering problems.

Combination of isotope dilution with liquid chromatography-inductively coupled plasma mass spectrometry for the simultaneous monitoring and evaluation of cadmium and inorganic arsenic in polished rice.

A new monitoring and evaluation technique for cadmium (Cd) and inorganic arsenic (i-As) in rice was developed, where the isotope dilution (ID) method was applied in combination with high performance liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS), following heat-assisted extraction. Cadmium and i-As in a rice sample were extracted using the HNO3-H2O2 extractant, and an appropriate amount of enriched 111Cd was spiked into it. Cadmium and As species were measured simultaneously by LC-ICP-MS. The cadmium concentration was calculated from the isotope dilution analysis, and i-As was determined by the comparison (1 point calibration) method using additional 111Cd as an internal standard. The proposed method provides accurate and precise determination of Cd based on the isotope dilution analysis. Moreover, it can be applied to a rapid screening test to find contaminated rice samples, by means of monitoring the intensity ratios of natural 111Cd and i-As to the additional 111Cd. The developed technique was applied to analyzing multiple rice reference materials, and the measurement results of Cd and i-As agreed with the certified values within the uncertainty range. It is noted that the grain size of rice samples does not affect the extraction data, when the rice sample is crushed into powder less than 850 μm. The proposed method was very useful for the monitoring and evaluation of Cd and i-As in rice as a precise analytical method as well as a screening method.

Development and Validation of Analytical Method by HPLC-PDA and Seasonality from Gallic Acid, Catechin, and Epicatechin in Leaf Extracts from Campomanesia adamantium

Campomanesia adamantium is native of the Brazilian Cerrado, and its leaves are popularly used as anti-inflammatory, antidiarrheal, and antiseptic in the urinary tract. This study aimed to develop and validate an analytical method by high-performance liquid chromatography for the simultaneous quantification and evaluation of the seasonal variability of gallic acid, catechin, and epicatechin, during 12 months, in C. adamantium leaf extracts. Chromatographic separations were performed with a mobile phase gradient of acetonitrile and 0.05% (v/v) trifluoroacetic acid solution, flow rate of 1.0 mL min-1, detection at 210 nm, C18 column (150 × 4.6 mm, 5 μm) and column oven temperature of 35 °C. The analytical method developed was selective, linear, precise, accurate, robust, and without matrix effect. The parameters obtained in the present study meet the requirements established by national and international guidelines. The best time for leaves harvesting, with the highest levels reached, was in September (0.0626%, m/v) and August (0.044%, m/v) for gallic acid, in June (0.3953%, m/v) and July (0.3804%, m/v) for catechin, and from May (0.1622%, m/v) and June (0.1415%, m/v) for epicatechin, in the dry season. Therefore, this study contributes by providing parameters for quality control of the raw material C. adamantium.