Effects of Carbidopa Premedication on 18F-FDOPA PET Imaging of Glioma: A Multiparametric Analysis

Purpose: This study aimed to determine the impact of carbidopa premedication on static, dynamic and radiomics parameters of 18F-FDOPA PET in brain tumors. Methods: The study included 54 patients, 18 of whom received carbidopa, who underwent 18F-FDOPA PET for newly diagnosed gliomas. SUV-derived, 105 radiomics features and TTP dynamic parameters were extracted from volumes of interest in healthy brains and tumors. Simulation of the effects of carbidopa on time-activity curves were generated. Results: All static and TTP dynamic parameters were significantly higher in healthy brain regions of premedicated patients (ΔSUVmean = +53%, ΔTTP = +48%, p < 0.001). Furthermore, carbidopa impacted 81% of radiomics features, of which 92% correlated with SUVmean (absolute correlation coefficient ≥ 0.4). In tumors, premedication with carbidopa was an independent predictor of SUVmean (ΔSUVmean = +52%, p < 0.001) and TTP (ΔTTP = +24%, p = 0.025). All parameters were no longer significantly modified by carbidopa premedication when using ratios to healthy brain. Simulated data confirmed that carbidopa leads to higher tumor TTP values, corrected by the ratios. Conclusion: In 18F-FDOPA PET, carbidopa induces similarly higher SUV and TTP dynamic parameters and similarly impacts SUV-dependent radiomics in healthy brain and tumor regions, which is compensated for by correcting for the tumor-to-healthy-brain ratio. This is a significant advantage for multicentric study harmonization.

Effects of carbidopa premedication on 18F-FDOPA PET imaging of brain tumors: a static, dynamic and radiomics analysis

Purpose This study aims to determine the impact of carbidopa premedication on static, dynamic and radiomics parameters of 18F-FDOPA PET imaging in brain tumors. Material and Methods The study included 54 patients that underwent 18F-FDOPA PET imaging for newly diagnosed gliomas. Among these, 18 patients received 100 mg of carbidopa. SUV parameters and 105 radiomics features were extracted from the static images. Dynamic data were available for 41 patients. Time to Peak (TTP) values were extracted from dynamic acquisitions. These parameters were obtained from volumes of interest in healthy brain as well as tumors. Simulation of the effects of carbidopa premedication on TTP values were also generated. Results All static and TTP dynamic parameters were significantly increased in healthy brain regions of premedicated patients (ΔSUVmean = + 53%, ΔTTP = + 48%, p < 0.001). Furthermore, carbidopa impacted 81% of radiomics features, of which 92% correlated with SUVmean (absolute correlation coefficient ≥ 0.4). In tumors, premedication with carbidopa was an independent predictor of SUVmean (ΔSUVmean = + 52%, p < 0.001) and TTP (ΔTTP = + 24%, p = 0.025). Interestingly, all parameters were no longer significantly modified by carbidopa premedication when using tumor-to-healthy-brain image and TAC ratios. Simulated data confirmed that carbidopa leads to an increase in tumor TTP values which is corrected by using these ratios. Conclusion In 18F-FDOPA PET brain imaging, carbidopa induces an increase of similar magnitude in SUV, SUV-dependent radiomics and TTP dynamic parameters in healthy brain and tumor regions which are compensated for after using the tumor-to-healthy-brain image and TAC ratios which is an important point for multicentric studies harmonization.

A Hybrid MCDM Approach towards Resilient Sourcing

Achieving a supply chain that is resilient to potential unforeseen disruptions (e.g., strikes, floods, tsunamis, etc.) remains one of the vital concerns of decision makers (DMs). To build up a reactive supply chain plan towards resilience, the purchasing department needs to pay the strictest attention to sourcing decisions. This study contributes to the literature through developing an efficient resilient supplier selection approach based on a new holistic framework that enables the identification of key resilience pillars (RPs) and traditional business criteria (TBC) in light of a thorough literature review and experts’ opinions. To this end, the relative importance of TBC/RP was measured by applying the DEMATEL (D) method. This was followed by the application of MABAC-OCRA-TOPSIS-VIKOR (MOTV) methods to verify the suppliers’ ranking. Furthermore, the Spearman rank correlation coefficient (SRCC) approach was used to investigate the correlation among the suppliers’ ranking, revealed via the four methods. In this work, a real sourcing problem of scrap metal for a steel manufacturing company was solved to prove the applicability of the proposed approach. The research outcome revealed that the TBC of “trust” is the most important criterion, followed by the “cost”, leaving the “geographical location” criterion as the least important one. In this context, the RP of “flexibility” attained the highest relative weight compared to “agility”, which secured the lowest weight. The results also showed “absolute” correlation among MABAC, VIKOR, and OCRA compared to “very strong” correlation between TOPSIS and the others. This research can support supply chain managers to achieve supply chain systems that reduce not only sourcing costs, but also potential losses because of disrupting threats, by building resilient supply chains.

A Rapid and Highly Predictive in vitro Screening Platform for Osteogenic Natural Compounds Using Human Runx2 Transcriptional Activity in Mesenchymal Stem Cells

The rapid aging of worldwide populations had led to epidemic increases in the incidence of osteoporosis (OP), but while treatments are available, high cost, adverse effects, and poor compliance continue to be significant problems. Naturally occurring plant-based compounds including phytoestrogens can be good and safe candidates to treat OP, but screening for osteogenic capacity has been difficult to achieve, largely due to the requirement of using primary osteoblasts or mesenchymal stem cells (MSCs), the progenitors of osteoblasts, to conduct time-consuming in vitro and in vivo osteogenic assay. Taking advantage of MSC osteogenic capacity and utilizing a promoter reporter assay for Runx2, the master osteogenesis transcription factor, we developed a rapid in vitro screening platform to screen osteogenic small molecules including natural plant-based compounds. We screened eight plant-derived compounds from different families including flavonoids, polyphenolic compounds, alkaloids, and isothiocyanates for osteogenic capacity using the human RUNX2-promoter luciferase reporter (hRUNX2-luc) transduced into the mouse MSC line, C3H10T1/2, with daidzein—a well-studied osteogenic phytoestrogen—as a positive control. Classical in vitro and in vivo osteogenesis assays were performed using primary murine and human bone marrow MSCs (BMMSCs) to validate the accuracy of this rapid screening platform. Using the MSC/hRUNX2-luc screening platform, we were able not only to shorten the selection process for osteogenic compounds from 3∼4 weeks to just a few days but also simultaneously perform comparisons between multiple compounds to assess relative osteogenic potency. Predictive analyses revealed nearly absolute correlation of the MSC/hRUNX2-luc reporter platform to the in vitro classical functional assay of mineralization using murine BMMSCs. Validation using human BMMSCs with in vitro mineralization and in vivo osteogenesis assays also demonstrated nearly absolute correlation to the MSC/hRUNX2-luc reporter results. Our findings therefore demonstrate that the MSC/hRUNX2 reporter platform can accurately, rapidly, and robustly screen for candidate osteogenic compounds and thus be relevant for therapeutic application in OP.

Identification and Reproducibility of Plasma Metabolomic Biomarkers of Habitual Food Intake in a US Diet Validation Study

Previous metabolomic studies have identified putative blood biomarkers of dietary intake. These biomarkers need to be replicated in other populations and tested for reproducibility over time for the potential use in future epidemiological studies. We conducted a metabolomics analysis among 671 racially/ethnically diverse men and women included in a diet validation study to examine the correlation between >100 food groups/items (101 by a food frequency questionnaire (FFQ), 105 by 24-h diet recalls (24HRs)) with 1141 metabolites measured in fasting plasma sample replicates, six months apart. Diet–metabolite associations were examined by Pearson’s partial correlation analysis. Biomarker reproducibility was assessed using intraclass correlation coefficients (ICCs). A total of 677 diet–metabolite associations were identified after Bonferroni adjustment for multiple comparisons and restricting absolute correlation coefficients to greater than 0.2 (601 associations using the FFQ and 395 using 24HRs). The median ICCs of the 238 putative biomarkers was 0.56 (interquartile range 0.46–0.68). In this study, with repeated FFQs, 24HRs and plasma metabolic profiles, we identified several potentially novel food biomarkers and replicated others found in our previous study. Our findings contribute to the growing literature on food-based biomarkers and provide important information on biomarker reproducibility which could facilitate their utilization in future nutritional epidemiological studies.

CORRELATIONS BETWEEN LINEAR DIMENSIONS OF THE LUMBAR INTERVERTEBRAL DISCS AND SOMATOMETRIC PARAMETERS IN GIRLS AND IN WOMEN OF THE FIRST ADULTHOOD

The relationships between linear dimensions of the lumbar intervertebral discs (IVDL1-L2, IVDL2-L3, IVDL3-L4, IVDL4-L5) and somatometric parameters in girls and females of the first adulthood were investigated. The numerous relationships between the partial (height, sagittal and transverse sizes) linear dimensions and total sizes of the lumbar intervertebral discs in girls and women of the first adulthood (16-26 years) with their somatometric parameters were found. The linear dimensions of the lumbar intervertebral discs (height, sagittal and transverse sizes) were measured on the MRI images in the axial, sagittal and coronal plains. The arithmetic means of absolute correlation coefficients between particular and total individual sizes of IVDL1-L2, IVDL2-L3, IVDL3-L4, IVDL4-L5 and relative quantity with somatometric parameters were calculated with following results: arithmetic means of absolute correlation coefficients for particular individual sizes are within 0,120 - 0,170; for total sizes – 0,190; for ratio of the total sizes to the mass-growth coefficient – 0,507.

Continuous and discontinuous nominal expressions in flexible (or “free”) word order languages: Patterns and correlates

This study explores continuous and discontinuous word order patterns of multi-word nominal expressions in flexible word order languages (traditionally referred to as “free word order” or “non-configurational” languages). Besides describing syntagmatic patterns, this paper seeks to identify any functional or other correlates that can be associated with different word orders. The languages under investigation are a number of Australian languages as well as Vedic Sanskrit, all of which have long been known for their syntagmatic flexibility. With respect to continuous order, evidence from several of these languages suggests that default ordering is primarily governed by functional templates. Deviations from default order, while maintaining continuity, can be attributed to different types of “focus” interpretations or heaviness effects. With respect to discontinuous order, I identify three sub-types. The most widespread one, “Left-Edge Discontinuity”, involves one element placed in or near utterance-initial position. It shows a clear, if not an absolute, correlation with different kinds of focus interpretations, similarly to deviations from the default order in continuity. The other two types of discontinuity are linked to the behaviour of specific function words. Besides teasing out cross-linguistic similarities, this paper also sheds light on language-specific characteristics that affect the forms and functions of complex (i.e. multi-word) nominal expressions in flexible word order languages, such as the nature of 2nd position (“Wackernagel”) elements.

Ethno-political challenges: reflection in the theoretical discourse and tools of state national policy

Introduction. The multilayered and contradictory development of the world, countries and regions against the backdrop of the consequences of globalization and international confrontation complicates the formulation and solution of internal management tasks, the choice of the optimal strategy and tactics for responding to rapidly changing situations, or, conversely, attempts to revive archaic institutions that reject the values of intercivilization dialogue. The purpose of this article is to identify and evaluate the place of the ethno-political challenges among the tools of the state national policy of the Russian Federation evidenced with relevant strategic planning documents.Materials and methods. The research was based on the study of official documents of the Russian Federation in the framework of the goal-setting and contextual analysis of political discourse, taking into account the concept of articulation. Methods of systematic and comparative analysis, political diagnostics were also used.The results of the research. The analysis made it possible to detect a significant, but not absolute correlation in the interpretation of ethno-political challenges for Russia in the considered strategic planning documents of the Russian Federation. It is shown that the meaning-forming plots of the official discourse in the ethno-political perspective have a largely conservative essence, referring to traditional values, preserving the identity of Russia as a civilization. Simultaneously it emphasizes the rejection of insularity, isolation, calls for activity in the international stage in various formats, for internal transformations. A certain coincidence of priority tasks in the context of actualized challenges in the field of interethnic relations, regional and spatial development of the country is revealed.Discussion and conclusions. The necessity of clarifying some of the provisions of the current strategic planning documents of the Russian Federation and of eliminating bottlenecks in them that do not agree with the modern discursive practices and the needs of managing the ethno-political sphere is substantiated. The authors proposed measures for improving the legislative support of ethnological examination, its practical implementation, expanding sociological and ethno-political monitoring with the integration of structures at the federal and regional levels and increasing attention to the local (municipal) level, early diagnosis and prevention of conflict situations, support for domestic culture and art, moral shaping of the elite and the training of personnel reserve in the spirit of awareness of belonging to the all-Russian civil nation.

Which Are the Effects of Hard and Soft Equality Constraints on the Iterative Outlier Elimination Procedure?

In this paper we evaluate the effects of hard and soft constraints on the Iterative Data Snooping (IDS), an iterative outlier elimination procedure. Here, the measurements of a levelling geodetic network were classified according to the local redundancy and maximum absolute correlation between the outlier test statistics, referred to as clusters. We highlight that the larger the relaxation of the constraints, the higher the sensitivity indicators MDB (Minimal Detectable Bias) and MIB (Minimal Identifiable Bias) for both the clustering of measurements and the clustering of constraints. There are circumstances that increase the family-wise error rate (FWE) of the test statistics, increase the performance of the IDS. Under a scenario of soft constraints, one should set out at least three soft constraints in order to identify an outlier in the constraints. In general, hard constraints should be used in the stage of pre-processing data for the purpose of identifying and removing possible outlying measurements. In that process, one should opt to set out the redundant hard constraints. After identifying and removing possible outliers, the soft constraints should be employed to propagate their uncertainties to the model parameters during the process of least-squares estimation.

Classification of Indian States and Union Territories based on their Soil Macronutrient and Organic Carbon Profiles

Soil fertility determines the successful development of a plant, and therefore it is important to achieve food security. Imbalanced and inadequate use of chemical fertilizers, irregular irrigation and harmful cultural practices deplete the soil profile nutrient profile, which is critical for the successful crop production. This study presents the results of the classification of the states across India based on their soil macronutrient profile. The entanglement coefficient of Unweighted Pair Group Method with Arithmetic Mean (UPGMA) and the neighbour-joining method was 0.81. Absolute correlation values were determined among the different classes of the soil nitrogen content and the corresponding classes of the soil phosphorus content. The K-mean clustering method divided the states and union territories into the three clusters. Overall, this works represents the grouping of Indian soils based on their soil macronutrient and organic carbon content.