Decomposition analysis of global value chains: Uncovering vulnerable spots in a selected economy (the example of Czechia).

Recent global turmoil has added to the importance of food security issues and the sustainability of production processes worldwide. This study aims to uncover the degree of domestic industries' dependence on the international fragmentation of production processes and identify the countries of origin of those producers who have managed to displace domestic producers in corresponding Global Value Chains. Using data retrieved from the World Input-Output Database, we studied Czechia's example via demarcation of domestic value-added (DVA) shares from foreign ones in final domestic products. A declining trend in DVA signalises an ever-increasing dependence on foreign inputs. The conducted analysis allowed a VA-structure (and its dynamics for a sequence of years) to be clearly identified for final domestic products among 30 industries that virtually cover the entire economy. The most alarming finding is the marked reduction of DVA in food manufacturing, which points to a weakening of Czech food security. Realising all the connections within GVCs may help to identify vulnerable spots in domestic production processes and prepare adequate response mechanisms in potential situations of possible interruptions from the foreign side. The detailed explanation of the decomposition technique provided in the study can be used in similar analyses of other economies to reveal noteworthy trends and prepare response measures.

Energy Logistic Regression and Survival Model: Case Study of Russian Exports.

The importance of environmental sustainability is becoming more and more obvious, so the rationale behind long-term usage of solely non-renewable energy sources appeared questionable. This study aims to identify, using Kaplan-Meier survival analysis and logistic regressions, the main determinants that affect the duration of Russian non-renewable energy exports to different regions of the world. Data were retrieved from the databanks of the World Development Indicators (WDI), World Integrated Trade Solution (WITS), and the French Centre for Prospective studies and International Information (CEPII). The obtained results point to the fact that approximately 52% of energy products survive beyond their first year of trading, nearly 38% survive beyond the second year, and almost 18% survive to the twelfth year. The survival of Russian non-renewable energy exports differs depending on the region, and the affecting factors are of different importance. The duration of Russian non-renewable energy exports is significantly linked to Russia's GDP, Total export, and Initial export values. A decline in Russia's GDP by 1% is associated with an increasing probability of a spell ending by 2.9% on average, in turn growing Total export and Initial export values positively linked with the duration of non-renewable energy exports from Russia. These findings may have practical relevance for strategic actions aimed at approaching both energy security and environmental sustainability.

Dinámica relacionada con la edad de parámetros antropométricos craneofaciales y su asociación con el tipo de oclusión dental en seres humanos de ambos géneros de: 17 a 24 años / Age-related dynamics of craniofacial anthropometric parameters and their association with the type of dental occlusion in humans of both genders aged 17­24 years

El propósito del estudio fue analizar la dinámica de los cambios relacionados con la edad de las estructuras craneofaciales de acuerdo con los parámetros antropométricos en hombres y mujeres de 17 a 24 años, y determinar la correlación, definida por análisis antropométrico, entre las formas de morfología craneofacial y los tipos de anomalías dento-maxilares. Materiales y métodos: Se realizó un examen antropométrico de 851 individuos (418 hombres y 433 mujeres) de 17 a 24 años y la evaluación de 45 mediciones entre puntos de referencia de tejidos blandos. Además, se realizó una valoración odontológica general, que incluyó la clasificación de las anomalías dentomaxilares. Resultados: Se detectó que el ancho de la cabeza, el largo de la cabeza, así como el ancho de la mandíbula y el ancho morfológico facial en las hembras alcanzan valores máximos de crecimiento a la edad de 20 años. Además, se obtuvieron datos que indicaron la continuación del crecimiento de los parámetros antropométricos craneofaciales mencionados anteriormente en los hombres durante el período de transición de la adolescencia a la edad adulta. Conclusión: la mordida profunda distal es la anomalía dento-maxilar (DMAn) más común en hombres y mujeres bielorrusos de 17 a 24 años. Junto con esto, la frecuencia de ocurrencia de maloclusión de mordida profunda distal en individuos con morfología craneofacial dolicocefálica es mayor en hombres y mujeres en comparación con otras formas de morfología craneofacial. La mordida profunda distal se acompaña de la disminución de los parámetros antropométricos de la altura facial, en comparación con la mordida mesial y abierta en la que hay un aumento estadístico. Además, se observa una disminución estadística en el valor de la profundidad facial inferior en individuos diagnosticados con mordida distal, en comparación con individuos con mordida mesial y normal. Estos resultados obtenidos del análisis antropométrico podrían ser útiles en el diagnóstico de anomalías dentofaciales y dento-maxilares, y en la simulación de resultados de tratamiento estéticamente estables.

The purpose of the study was to analyze the dynamics of age-related changes of craniofacial structures according to anthropometric parameters in males and females aged 17­24 years, and to determine the correlation, defined by anthropometric analysis, between forms of craniofacial morphology and the type of dento-maxillary anomalies. Materials and Methods: An anthropometric examination of 851 individuals (418 males and 433 females) aged 17­24 years and the evaluation of 45 measurements between soft tissue landmarks was performed. In addition, general dental assessment was conducted, which included the classification of the dento-maxillary anomalies. Results: It was detected that the head width, head length, as well as the mandible width, and the morphological facial width in females reach growth peak values at the age of 20 years. Furthermore, data was obtained which indicated growth continuation of the stated above craniofacial anthropometric parameters in males during the transitional period from adolescence to adulthood. Conclusion: Distal deep bite is the most commonly prevailed dento-maxillary anomalies (DMAn) in Belarusian men and women aged 17­24 years. Along with this, the frequency of distal deep bite malocclusion occurrence in individuals with dolichocephalic craniofacial morphology is higher in men and women when compared to other forms of craniofacial morphology. Distal deep bite is accompanied by the decrease of facial height anthropometric parameters, when compared to mesial and open bite in which there is a statistical increase. Moreover, a statistical decrease in the value of the inferior facial depth is observed in individuals diagnosed with distal bite, when compared to individuals with mesial and normal bite. These obtained results from anthropometric analysis could be useful in diagnosis of dentofacial and dento-maxillary anomalies, and in the simulation of aesthetically stable treatment results

Investigating the dynamic eco-efficiency in agriculture sector of the European Union countries.

One of the main aims of European Common Agricultural Policy (CAP) has been established on a considerable reduction of greenhouse gas (GHG) emissions without any decline in productivity by 2030. This introduces some challenges in the assessment of agricultural technical efficiency. In particular, we can formulate at least two problems that are worth to be addressed: (i) possibility of treating undesirable outputs and (ii) panel data analysis of agricultural technical efficiency enriched by eco-efficiency assessment. In this study, we applied a Window Slack-Based Measurement Data Envelopment Analysis (W-SBM-DEA) model in the presence of undesirable outputs to evaluate the performance of agriculture sector of EU-27 countries during the period from 2008 to 2017. The country-level cultivated agricultural area, labor, specific costs, overheads, and depreciation were considered as the model inputs, and the gross value of country-level crop and livestock products represented the desirable outputs. The agricultural total GHG emissions at the country-level were accounted for as the undesirable output in the model. Having compared the results of different models, the substantial difference in the performance of the EU countries was registered mainly due to incorporating undesirable outputs and window analysis when using SBM-DEA model. The results of eco-efficiency assessment indicated that the Netherlands, Belgium, Italy, and Malta are the most eco-efficient countries with a score higher than 0.90, while the lowest eco-efficiency scores were reported for Slovakia, Latvia, and Estonia. The highest average eco-efficiency scores of all EU members were registered in 2011 (0.82), 2012 (0.83), and 2017 (0.84). A comparison of eco-efficiency performance between the old and new EU members indicated that the greater scores were obtained by old EU members. The variability assessment results showed a low variability and subsequently a high stability in the European agricultural sector, particularly in the Netherlands, Italy, and Malta. Based on our findings, it was concluded that for assessing agricultural technical efficiency in European agriculture in the context of eco-efficiency, application of a W-DEA model with undesirable output for a specified period of time reduces the impacts of temporary changes and provides more realistic results when comparing to models without undesirable output. These more realistic assessments of technical efficiency could help policy-makers to make more precise decisions.

Lentiviral gene therapy vector with UCOE stably restores function in iPSC-derived neutrophils of a CDG patient.

A recent gamma-retroviral clinical Chronic Granulomatous Disease (CGD) gene therapy (GT) trial achieved proof-of-concept but was accompanied by activation of oncogenes and transgene silencing. The ubiquitous chromatin opening element (UCOE) comprises the sequences of two divergently oriented house-keeping gene promoters and is known to have anti-silencing properties. In a screen we identified two novel UCOE constructs that prevent adjacent promoter methylation in P19 cells. Experiments were continued with the shorter UCOE constructs in induced pluripotent stem cells (iPSC) derived from a p47phox-deficient CGD patient. The iPSC line was transduced with the lentiviral GT vectors expressing P47 under the constitutively active SFFV promoter with UCOE element (UCOE_SF) and without UCOE element (SF) adjacent to the SFFV promoter. The iPSC were expanded before propagation towards neutrophils. 20 days after transduction the UCOE_SF vector was protected from methylation in iPSC as previously shown in P19 cells, whereas the SF vector was heavily methylated in iPSC. The UCOE_SF vector maintained stable transgene expression in iPSC, macrophages and neutrophils, whereas the SF vector was strongly silenced. The UCOE_SF vector stably restored ROS production in neutrophils, whereas for the SF vector the count of ROS producing cells was marginal. To conclude, we have shown that the prevention of transgene silencing by UCOE is functionally and mechanistically preserved upon terminal neutrophil differentiation.

Severe glucose-6-phosphate dehydrogenase deficiency leads to susceptibility to infection and absent NETosis.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells in human subjects, causing hemolytic anemia linked to impaired nicotinamide adenine dinucleotide phosphate (NADPH) production and imbalanced redox homeostasis in erythrocytes. Because G6PD is expressed by a variety of hematologic and nonhematologic cells, a broader clinical phenotype could be postulated in G6PD-deficient patients. We describe 3 brothers with severe G6PD deficiency and susceptibility to bacterial infection. OBJECTIVE: We sought to study the molecular pathophysiology leading to susceptibility to infection in 3 siblings with severe G6PD deficiency. METHODS: Blood samples of 3 patients with severe G6PD deficiency were analyzed for G6PD enzyme activity, cellular oxidized nicotinamide adenine dinucleotide phosphate/NADPH levels, phagocytic reactive oxygen species production, neutrophil extracellular trap (NET) formation, and neutrophil elastase translocation. RESULTS: In these 3 brothers strongly reduced NADPH oxidase function was found in granulocytes, leading to impaired NET formation. Defective NET formation has thus far been only observed in patients with the NADPH oxidase deficiency chronic granulomatous disease, who require antibiotic and antimycotic prophylaxis to prevent life-threatening bacterial and fungal infections. CONCLUSION: Because severe G6PD deficiency can be a phenocopy of chronic granulomatous disease with regard to the cellular and clinical phenotype, careful evaluation of neutrophil function seems mandatory in these patients to decide on appropriate anti-infective preventive measures. Determining the level of G6PD enzyme activity should be followed by analysis of reactive oxygen species production and NET formation to decide on required antibiotic and antimycotic prophylaxis.

Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing.

We report on a series of sequential events leading to long-term survival and cure of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma-retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (HSCT) but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following GT both children completely resolved invasive Aspergillus nidulans infections. However, one child developed dual insertional activation of ecotropic viral integration site 1 (EVI1) and signal transducer and activator of transcription 3 (STAT3) genes, leading to myelodysplastic syndrome (MDS) with monosomy 7. Despite resistance to mismatched allo-HSCT with standard myeloablative conditioning, secondary intensified rescue allo-HSCT resulted in 100 % donor chimerism and disappearance of MDS. The other child did not develop MDS despite expansion of a clone with a single insertion in the myelodysplasia syndrome 1 (MDS1) gene and was cured by early standard allo-HSCT. The slowly developing dominance of clones harboring integrations in MDS1-EVI1 may guide clinical intervention strategies, i.e. early rescue allo-HSCT, prior to malignant transformation. GT was essential for both children to survive and to clear therapy-refractory infections, and future GT with safer lentiviral self-inactivated (SIN) vectors may offer a therapeutic alternative for X-CGD patients suffering from life-threatening infections and lacking HLA-identical HSC donors.

Human miR223 promoter as a novel myelo-specific promoter for chronic granulomatous disease gene therapy.

Targeting transgene expression to specific hematopoietic cell lineages could contribute to the safety of retroviral vectors in gene therapeutic applications. Chronic granulomatous disease (CGD), a defect of phagocytic cells, can be managed by gene therapy, using retroviral vectors with targeted expression to myeloid cells. In this context, we analyzed the myelospecificity of the human miR223 promoter, which is known to be strongly upregulated during myeloid differentiation, to drive myeloid-restricted expression of p47(phox) and gp91(phox) in mouse models of CGD and in primary patient-derived cells. The miR223 promoter restricted the expression of p47(phox), gp91(phox), and green fluorescent protein (GFP) within self-inactivating (SIN) gamma- and lentiviral vectors to granulocytes and macrophages, with only marginal expression in lymphocytes or hematopoietic stem and progenitor cells. Furthermore, gene transfer into primary CD34+ cells derived from a p47(phox) patient followed by ex vivo differentiation to neutrophils resulted in restoration of Escherichia coli killing activity by miR223 promoter-mediated p47(phox) expression. These results indicate that the miR223 promoter as an internal promoter within SIN gene therapy vectors is able to efficiently correct the CGD phenotype with negligible activity in hematopoietic progenitors, thereby limiting the risk of insertional oncogenesis and development of clonal dominance.

Association of hypoalbuminemia with the presence and size of pleural effusion in children with pneumonia.

OBJECTIVE: Hypoalbuminemia is a common finding in children with massive parapneumonic pleural effusion; however, its incidence and pathogenesis are unclear. The objective of this study was to assess the presence and severity of hypoalbuminemia in children with parapneumonic pleural effusion and to propose a possible pathophysiologic mechanism. METHODS: The clinical charts of patients who were hospitalized in a tertiary pediatric center with bacterial pneumonia complicated by pleural effusion were reviewed. The volume of pleural fluid was assessed semiquantitatively and categorized as small, moderate, or large. The lowest serum albumin level was recorded, and caloric intake and protein loss were evaluated. Findings were compared with age- and gender-matched children who had bacterial pneumonia without pleural effusion and with children who had acute illnesses other than pneumonia. RESULTS: Of the 50 patients in the study group, 15 (30%) had small effusions, 16 (32%) had moderate effusions, and 19 (38%) had large effusions. Moderate-to-severe hypoalbuminemia was found in 52% of the study group, 6% of the patients with pneumonia without pleural effusion, and none of the patients with other illnesses. Mean serum albumin level was lower in patients with large pleural effusions than in patients with small effusions (2.66 +/- 0.37 vs 3.66 +/- 0.47 g/dL). There was no evidence of albumin loss or significant malnutrition. Estimation of the amount of albumin in the drained pleural fluid suggested an albumin shift from blood to pleural fluid. CONCLUSIONS: Significant hypoalbuminemia is common in children with parapneumonic pleural effusion. Large effusions are associated with low serum albumin levels, which might be explained in part by a shift from blood to pleural fluid.

Caveolae: biochemical analysis.

Caveolae appear in a multitude of processes encompassing growth regulation and trafficking. We demonstrate the abundant presence of ESA/reggie-1/flotillin-2, ATP synthase beta subunit and annexin V in endothelial caveolae by immunopurification of caveolae from vascular endothelial membrane. Five proteins are abundant in a caveolin-1 protein complex, analyzed by sucrose gradient velocity sedimentation following octyl-beta-D-glucopyranoside extraction. Caveolin-1 alpha interacts with caveolin-1beta, caveolin-2, actin, the microsomal form of NADH cytochrome B5 reductase and ESA/reggie-1/flotillin-2 as shown by co-immunoprecipitation. We propose the concept that ATP biosynthesis in caveolae regulates mechanosignaling and is induced by membrane depolarization and a proton gradient. Pressure stimuli and metabolic changes may trigger gene regulation in endothelial cells, involving a nuclear conformer of caveolin-1, shown here with an epitope-specific caveolin-1 antibody, and immediate response of ion channel activity, regulated by ESA/reggie-1/flotillin-2.

LDL transcytosis by protein membrane diffusion.

Endothelial cell (EC) cultures of different, selected vascular beds and/or organs were screened for receptor-mediated transport of proteins with a semipermeable filter assay. In SVEC4-10 cells, a mouse lymphoid endothelial cell line, orosomucoid, albumin, insulin and LDL were transcytosed from the apical (luminal) to basal (abluminal) side by a receptor-mediated pathway. Specific LDL transcytosis involved transport of intact LDL. A pathway of degradation of LDL and basal release involved vesicles in transport to lysosomes and amino acid merocrine secretion. This newly described transcellular passage of LDL via lysosomes, as well as the standard pathway, were reduced to 70% by PEG(50)-cholesterol (PEG-Chol). Combined results of temperature-dependence analysis and PEG(50)-cholesterol sensitivity show that two pathways contribute to general LDL transcellular passage. We suggest a mechanism of domain hopping by protein membrane diffusion of receptors as the pathway for intact LDL delivery. Based on theoretical considerations we propose that active transport by protein membrane diffusion can be facilitated by an organizational structure of lipid microdomains and polar cellular organization.