Aggregation Response Research Articles

A study of platelet function in patients with chronic immune thrombocytopenia treated with thrombopoietin receptor agonists

BackgroundThrombopoietin receptor agonists (TPO-RAs) are widely used in immune thrombocytopenia (ITP) and are associated with increased thrombotic risk. However, data regarding their impact on platelet function is scarce. MethodsPlatelet function was evaluated in chronic ITP patients enrolled over one year, using light transmission aggregometry and platelet-derived microparticle (PMP) levels measurement with flow cytometry. Aggregation responses to various concentrations of ADP, collagen, ristocetin, and PMP levels were compared between TPO-RA-treated patients, patients treated with other agents and healthy individuals. ResultsTPO-RA-treated patients (n = 24) displayed significantly reduced aggregation responses to 2.5 μM, 5 μM, and 10 μM of ADP and collagen compared to 15 healthy individuals (59.5 % vs. 87.6 %, p < .0001, 43.6 % vs. 79.9 %, p < .0001, 26.1 % vs. 75.2 %, p < .0001, 67.2 % vs. 86 %, p < .0001, respectively). Reduced responses to ADP and collagen were also recorded in patients treated with other agents (n = 16) compared to healthy controls but without difference between the two treatment groups. Aggregation response to ristocetin was normal in all three groups. None of the patients yielded enhanced platelet aggregation. In TPO-RA-treated patients, a strong positive correlation between platelet counts and aggregation response to ristocetin was observed (rs = 0.65, p = .0005). PMP levels were significantly elevated in TPO-RA-treated patients compared to patients treated with other agents (49.5 vs 4.5 events/uL, p < .0001) and healthy controls (5 events/uL, p < .0001). ConclusionsThese results suggest that TPO-RAs may not enhance platelet aggregation responses, whereas impaired responses may be a disease feature. Furthermore, TPO-RAs may increase PMP levels and thus be implicated in the modulation of platelet function in ITP patients.

Platelet antiaggregant activity of Hypericum perforatum extracts

BackgroundIn addition to its potential use as an antidepressant, different studies have shown that Hypericum perforatum (HP) can have antibacterial, antioxidant, and antiviral properties. Despite this potential, most of the therapeutic bioactivities attributed to HP need further scientific support. In a previous study we found an inhibitory effect of HP in platelet activation markers. So, in the present work we investigate the effect of HP in another aspect of platelet function, platelet aggregation. MethodsFirst, the effect of different concentrations of the total alcoholic extract of HP on platelet aggregation was studied in 9 healthy donors by aggregometry methods using collagen as agonist. After that, to obtain dose-effect curves, 3 experiments were carried out independently in a single individual using collagen, adenosine diphosphate and epinephrine as agonists. ResultsOur results reveal a marked inter-individual variability and a significant dose-dependent decrease of aggregation responses induced by collagen in the presence of HP extracts (mean of minimum inhibition: 8% at a dose of 0.068 mg es/ml and mean of maximum inhibition: 43% at a dose of 0.456 mg es/ml). With the results obtained it was possible to obtained a IC50 value of 0.34 mg es/ml. ConclusionsWe can conclude that HP has a dose-dependent inhibitory effect on platelet function (activation and aggregation responses), therefore, our results suggest that HP may be recognized as an herbal medicine with anti-platelet properties.

Lipopolysaccharide from Proteus mirabilis Slows Platelet Plug Formation in Human Whole Blood

Platelets are well known for their role in hemostasis. Additionally, platelets play a crucial role in immune and inflammatory responses. Toll-like receptors (TLRs) can mediate bacterial interactions during infection, triggering platelets to initiate an inflammatory response. TLR-4 receptors enable direct interactions between platelets and the bacterial lipopolysaccharide (LPS) endotoxin. The aim of this study was to assess platelet plug formation in response to LPS from Proteus mirabilis. Human whole blood was treated with varying concentrations of LPS over a range of incubation times. Then, platelet plug formation time was measured, under high shear conditions using the platelet function analyzer PFA-100, as aperture closure time (CT). The addition of either 2 or 10 µg/mL of LPS to 80% whole blood significantly prolonged the CTs even in the absence of preincubation (p = 0.028 or p = 0.049, respectively). With added preincubation of LPS with whole blood, the measured CTs were further prolonged. If the preincubation time was set to 35 min, then even the addition of 0.2 µg/mL of LPS resulted in significant CT prolongation (p &lt; 0.001). Taken together, the platelet plug formation in the presence of collagen/ADP is significantly prolonged by the presence of LPS in a concentration and preincubation time-dependent manner. Exposure to P. mirabilis LPS reduces the platelet aggregation response in human whole blood.

Enhancement of heat transfer characteristics in wavy microchannel heat sinks with streamlined micropins within convergent-divergent flow passages

In the current study, the heat transfer characteristics of a novel design microchannel with a wavy sinusoidal convergent-divergent wall structure featuring streamlined pins have been numerically investigated under laminar flow conditions. Various amplitudes, wavelengths, pin heights, and Reynolds numbers are considered as parameters. The thermal and hydraulic characteristics are analyzed in terms of Nusselt number, Fanning friction factor, and Performance Evaluation Criteria number (PEC), which evaluates the heat transfer enhancement against the associated pressure drop. It is revealed that increasing the amplitude and decreasing wavelength, along with moderate pin heights, significantly augment heat transfer. The streamlined pins effectively direct the flow, and the resulting secondary flow and chaotic advection considerably enhance heat transfer in the designed configuration. The study demonstrates that the heat transfer can be improved by a factor of 4.79 compared to a straight microchannel. Under these geometric and flow conditions, the pressure drop increases by a factor of 9.87, and the PEC is found to be around 2.23. A multi-objective optimization study using the Non-dominated Sorting Genetic Algorithm (NSGA-II) is conducted with Genetic Aggregation Response Surface Methodology to evaluate the impact of various parameters on thermal-flow performance and to identify the optimal design with material quantity variation. According to the optimal results, a 5 % increase in material can augment thermal-flow performance by approximately 206.6 % compared to traditional microchannels. Finally, practical correlations for the Nusselt number and friction factor, accounting for various parameters, have been developed to facilitate in designing of microchannel cooling systems.

The effects of roots and earthworms on aggregate size distribution and their associated carbon under contrasting soil types and soil moisture conditions

Soil’s potential as a carbon sink is uncertain due to biotic and abiotic interactions. Soil aggregates are important carriers of organic carbon (OC), and clarifying the response of aggregates and their associated OC to plant roots and earthworms can better understand the carbon cycle in terrestrial ecosystems. Herein, we determined the regulatory role of plant roots (Lolium perenne) and earthworms (Metaphire tschiliensis) in isolation and in combination on aggregate size distribution and their associated OC and readily oxidizable OC (ROOC) under contrasting soil types (Phaeozems and Anthrosols) and soil moisture conditions (constant wetting, CW; wetting–drying cycle repeated four times, 4WD) by a laboratory microcosm experiment. Results showed that earthworm presence significantly increased plant biomass by 30 % and 221 % in Phaeozems and Anthrosols, respectively (p < 0.05). For Phaeozems, plant alone (P) and plant and earthworm in combination (PE) had lower proportion of large aggregate (5–8 and 2–5 mm) than bare soil (CK) under 4WD condition (p < 0.05). For Anthrosols, the PE treatment decreased the proportion of 5–8 and 2–5 mm aggregate by 45 % and 25 %, respectively, under CW condition, and decreased the proportion of 5–8 mm aggregate by 37 % under 4WD condition (p < 0.05). Moreover, the proportion of 5–8 and 2–5 mm aggregate in P treatment was lower under CW condition (6.92 % and 22.13 %) but was higher under 4WD condition (11.49 % and 32.55 %) than those in CK (14.69 % and 29.91 %; 8.85 % and 20.56 %) (p < 0.05). Our results further indicated that the PE treatment had relatively higher OC and ROOC contents, especially for small aggregates in Anthrosols. The study indicates that plant roots and earthworms significantly influence aggregate turnover and the carbon cycle, with soil type and moisture playing a crucial role.

How biotic interactions structure species' responses to perturbations.

Predicting how ecological communities will respond to disturbances is notoriously challenging, especially given the variability in species' responses within the same community. Focusing solely on aggregate responses may obscure extinction risks for certain species owing to compensatory effects, emphasizing the need to understand the drivers of the response variability at the species level. Yet, these drivers remain poorly understood. Here, we reveal that despite the typical complexity of biotic interaction networks, species' responses follow a discernible pattern. Specifically, we demonstrate that the species whose population abundances are most reduced by biotic interactions-which are not always the rarest species-are those that exhibit the strongest responses to disturbances. This insight enables us to pinpoint sensitive species within communities without requiring precise information about biotic interactions. Our novel approach introduces avenues for future research aimed at identifying sensitive species and elucidating their impacts on entire communities.

Impact of Multi versus Single Arterial Coronary Bypass Graft Surgery on Postoperative Atrial Fibrillation

The effect of multi-arterial (MA) versus single arterial (SA) coronary bypass graft surgery on postoperative atrial fibrillation (POAF) was not investigated. From May 2017 to May 2024, the patients with CYP2C19*2 or *3 allele receiving coronary artery grafting and post-operational aspirin 100 mg/day and clopidogrel 75mg/day were retrospectively reviewed and assigned into MA or SA group. The primary endpoint was the incidence rate of POAF in first week. The secondary endpoints were POAF burden, platelet aggregation, systemic immune-inflammation (SII) index and heart rate variability (HRV). The study included 58 cases in MA group and 174 cases in SA group. The incidence of POAF was 17% in MA group contrasting with 42% in SA group (hazard ratio: 0.353; 95% confidence interval: 0.218 to 0.569, P=0.0012). A lower POAF burden was observed in MA group than that in SA group (2 h [1, 5] versus 10 h [6, 20], P=0.02). Platelet aggregation (arachidonic acid, 46%±10% vs. 56%±8%, P<0.01; adenosine diphosphate, 58%±17% vs. 75%±13%, P<0.01) and inflammation response index (neutrophil-lymphocyte ratio, 26±4 vs. 28±5, P=0.006; SII index, 5019±771 vs. 5382±1204, P=0.032) was notably lower in MA group than those in SA group at one day after CABG. Holter electrocardiogram showed a higher HRV value in standard deviation of normal-to-normal RR intervals, and decreased low-frequency/high-frequency ratio in MA group. In conclusion, MA was associated with a lower incidence rate of POAF, and paralleled with a lower AF burden, platelet aggregation, inflammation reaction and a higher parasympathetic nerve tone compared with SA regimen.

Divergent responses of soil aggregation and aggregate-carbon to fertilization regimes jointly explain soil organic carbon accrual in agroecosystems: A meta-analysis

Soil aggregation can be substantially affected by fertilizers and contributes to soil organic carbon (SOC) sequestration in agroecosystems. However, the mass and C distributions in different aggregates in responses to fertilization regimes are not often synchronous, which may largely affect soil C storage and stability. We conducted a meta-analysis of 2440 paired observations from 63 publications to assess the fertilization effects (i.e. inorganic, organic, and their combinations) on soil aggregation and aggregate-associated OC, as well as their linkages to the stimulated bulk soil C. Overall, fertilizer application significantly increased the mean weight diameter of soil aggregates by 27.8%. The proportion of large (> 2mm) and small (0.25-2mm) macroaggregates were significantly increased by 19.8% and 17.2%, and that of microaggregate (0.053-0.25mm) and silt-clay fraction (< 0.053mm) were significantly decreased by 6.0% and 18.4%, respectively. In contrast, fertilization significantly increased C concentration in all aggregates. Organic fertilizer applications had remarkably greater effects than inorganic fertilizer applications on soil C concentration but the effects declined with decreasing aggregate size (from 36.5% to 13.2%), while that of inorganic application changed very little among aggregates (from 14.1% to 10.0%). The fertilizer effects on soil aggregation and aggregate-associated OC divergently responded to the gradients of major agronomic conditions (i.e. climate, soil properties, and duration). Organic fertilizer applications tended to have distinctly greater promotion effect than solely inorganic fertilizer applications with temperate climate, neutral-to-alkaline pH and more sand-like texture of soil. The importance of mineral- rather than larger size aggregate-associated OC in contributing to the bulk SOC pool tended to increase in the long term. The inorganic-organic combinations exhibited the most lasting effect on SOC accrual. In conclusion, the responses of bulk soil C to fertilizer applications were not always in accordance with those of soil aggregation, but can be well explained when jointly considering soil aggregate C. Our findings highlight the varying contributions of aggregates to the soil C pool in diverse and complicated agronomic situations, which are important to the agricultural C sink stability.

The role of inflammation biomarkers in carotid artery stenosis procedures

BackgroundCarotid revascularization procedures, such as carotid endarterectomy (CEA) and carotid artery stenting (CAS), can lead to restenosis. Monitoring restenosis onset through biomarkers is crucial in clinical practice. This study aimed to evaluate inflammation biomarkers in CEA and CAS to determine their predictive value for restenosis risk post-procedure. MethodsA retrospective analysis was conducted on the clinical records of patients with carotid stenosis who underwent CEA or CAS over one year at the Vascular Surgery departments of an interuniversity center. Eligible asymptomatic patients with carotid stenosis (70-99%) underwent revascularization. Differences between pre- and early post-procedural inflammation indices were assessed, and restenosis risk was evaluated using Receiver Operating Curve analysis and logistic regression. ResultsThe cohort comprised 100 patients, 68 undergoing CEA and 32 undergoing CAS. Significant values were observed for inflammation ratios post-CEA: neutrophils to lymphocytes ratio (NLR) (p=0.036), platelets to lymphocytes ratio (PLR) (p=0.009), monocytes to lymphocytes ratio (MLR) (p<0.001), systemic inflammation index (SII) (p=0.024), systemic immune response index (SIRI) (p=0.003), and aggregate inflammation response index (AISI) (p<0.001). At 12-month follow-up, 12% of patients experienced restenosis; 50% were men and 50% women. Women showed a higher restenosis rate (26.1% vs 7.8%). Pre-intervention NLR (OR [95% CI] = 13.38 [1.88 to 95.44], p=0.010) and SIRI (OR [95% CI] = 10.22 [2.65 to 39.43], p=0.001) remained significantly associated with restenosis after adjusting for sex and smoking. ConclusionThe study provided a predictive model for restenosis, identifying pre-intervention NLR and SIRI as independent predictors of restenosis at 12-month follow-up.

Glycation Produces Topologically Different α-Synuclein Oligomeric Strains and Modulates Microglia Response via the NLRP3-Inflammasome Pathway.

α-Synuclein, a key player in Parkinson's disease and other synucleinopathies, possesses an inherently disordered structure that allows for versatile structural changes during aggregation. Microglia, the brain immune cells, respond differently to various α-synuclein strains, influencing their activation and release of harmful molecules, leading to neuronal death. Post-translational modifications, such as glycation in α-synuclein, add a layer of complexity to microglial activation. This study aimed to explore the impact of glycation on α-synuclein aggregation and microglial responses, which have not been studied before. Biophysical analyses revealed that glycated α-synuclein oligomers had distinct morphologies with a more negative and hydrophobic surface, preventing fibril formation and interfering with membrane interactions. Notably, there was increased cytosolic Ca2+ dysregulation, redox stress, and mitochondrial instability compared to cells exposed to unmodified α-synuclein oligomers. Additionally, glycated α-synuclein oligomers exhibited impaired binding to Toll-like receptor 2, compromising downstream signaling. Surprisingly, these oligomers promoted TLR4 endocytosis and degradation. In our experiments with oligomers, glycated α-synuclein oligomers preferred NLRP3 inflammasome-mediated neuroinflammation, contributing differently from unmodified α-synuclein oligomers. In summary, this study unveils the mechanism underlying the effect of glycation on α-synuclein oligomers and highlights the conformation-specific microglial responses toward extracellular α-synuclein.

Abstract B104: Identifying gaps in equitable cancer care: insights from US-based oncology professionals engaged in continuing medical education

Abstract Introduction: A previous evaluation of a five-part accredited continuing medical education (CME) designed to inspire action for equitable cancer care amongst US-based multidisciplinary oncology care team members, showed significant improvements in relevant knowledge and confidence (pre to post activity). This study aimed to revisit the data collected in the scope of this project to identify remaining challenges in ensuring equitable cancer care is delivered to all patients, with underlying gaps in knowledge, confidence and attitude that may be addressed through future CME. Methods: A secondary analysis of data was performed on quantitative (case-based multiple-choice) responses collected from US-based HCPs who completed at least one of the five accredited CME activities that were part of the program titled “Addressing Racial Disparities in Cancer Care”. Questions assessed learners’ knowledge, confidence, and attitudes after exposure to the CME. Crosstabulations with chi-square statistical tests compared quantitative responses by sub-group. The analysis focused on post-CME data to identify remaining educational gaps, with the aim of informing the development of future CME programs. Results: The five-part CME education reached 1151 unique HCPs involved in cancer care, with activity participation varying between n=103 to n=433. The profession/specialty sub-group most represented in aggregated responses across the five-part CME were registered nurses specialized in hematology/oncology (n=575/1145, 50%). Across US regions, respondents were mostly located in South US (n=446/1150, 39%). A challenge in helping patients navigate socio- economic barriers to oncology care was found, with the following four related gaps affecting a portion of respondents post-CME exposure: 1) misconception that the most important determinant of treatment adherence is a patient’s perceived treatment efficacy rather than optimal patient-provider communication (n=57/400, 14%), 2) sub-optimal knowledge of the impact of a patient’s community and/or partner on influencing their treatment-seeking behavior (n=31/97, 32%), 3) sub-optimal knowledge of necessary steps to address the root cause of a patients’ missed appointments (n=36/227, 16%), 4) sub-optimal confidence in addressing a patients’ personal circumstances limiting their access to cancer-care (n=424/1151, 37%). Conclusions: This study identified remaining gaps in knowledge, confidence and attitude among US-based HCPs post-exposure to a CME activity aimed at promoting equitable cancer care. Considering these gaps were observed post-education, the actual proportion of US-based HCPs affected is likely underestimated. Future continuing learning initiatives aimed at addressing cancer care disparities in the US should consider targeting gaps identified in this study by challenging learners to re-consider their knowledge, beliefs and confidence in best approaches to navigating the socio-economic barriers hindering patients from seeking cancer care (e.g., via adaptive learning, peer-to-peer learning). Citation Format: Monica Augustyniak, Karen Eldridge, Jayne Gurtler, Benyam Muluneh, Amy DePue, Julia Rodriguez-O'Donnell, Stacy Atkinson, Sophie Péloquin, Ann Murphy, Patrice Lazure. Identifying gaps in equitable cancer care: insights from US-based oncology professionals engaged in continuing medical education [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B104.

Identification of antibody targets associated with lower HIV viral load and viremic control.

High HIV viral loads (VL) are associated with increased morbidity, mortality, and on-going transmission. HIV controllers maintain low VLs in the absence of antiretroviral therapy (ART). We previously used a massively multiplexed antibody profiling assay (VirScan) to compare antibody profiles in HIV controllers and persons living with HIV (PWH) who were virally suppressed on ART. In this report, we used VirScan to evaluate whether antibody reactivity to specific HIV targets and broad reactivity across the HIV genome was associated with VL and controller status 1-2 years after infection. Samples were obtained from participants who acquired HIV infection in a community-randomized trial in Africa that evaluated an integrated strategy for HIV prevention (HPTN 071 PopART). Controller status was determined using VL and antiretroviral (ARV) drug data obtained at the seroconversion visit and 1 year later. Viremic controllers had VLs <2,000 copies/mL at both visits; non-controllers had VLs >2,000 copies/mL at both visits. Both groups had no ARV drugs detected at either visit. VirScan testing was performed at the second HIV-positive visit (1-2 years after HIV infection). The study cohort included 13 viremic controllers and 64 non-controllers. We identified ten clusters of homologous peptides that had high levels of antibody reactivity (three in gag, three in env, two in integrase, one in protease, and one in vpu). Reactivity to 43 peptides (eight unique epitopes) in six of these clusters was associated with lower VL; reactivity to six of the eight epitopes was associated with HIV controller status. Higher aggregate antibody reactivity across the eight epitopes (more epitopes targeted, higher mean reactivity across all epitopes) and across the HIV genome was also associated with lower VL and controller status. We identified HIV antibody targets associated with lower VL and HIV controller status 1-2 years after infection. Robust aggregate responses to these targets and broad antibody reactivity across the HIV genome were also associated with lower VL and controller status. These findings provide novel insights into the relationship between humoral immunity and viral containment that could help inform the design of antibody-based approaches for reducing HIV VL.

Commodity prices and production networks in small open economies

We study the role of domestic production networks in the transmission of commodity price fluctuations in small open economies. First, we present a tractable model of a small open economy's production network to explain sectoral propagation patterns. We demonstrate that the domestic production network is crucial in shaping the propagation of commodity prices. Using a panel of 31 sectors across 9 small open economies, we empirically confirm the model's predictions. Next, we construct a dynamic model of a small open economy featuring a production network to study the macroeconomic importance of the network structure in shaping both aggregate and sectoral responses to commodity price shocks. We show that: (i) the network-adjusted labor share of the commodity sector, rather than the sector's size, is key to understanding the real wage's response to commodity price fluctuations; and (ii) non-unitary elasticities of substitution in production are crucial for understanding the cross-sectional implications of these fluctuations.

How to construct monthly VAR proxies based on daily surprises in futures markets

It is common in applied work to estimate responses of macroeconomic aggregates to news shocks derived from surprise changes in daily futures prices around the date of policy announcements. This requires mapping the daily surprises into a monthly shock that may be used as an external instrument in a monthly VAR model or local projection. The standard approach has been to sum these daily surprises over the course of a given month when constructing the monthly proxy variable, ignoring the accounting relationship between daily and average monthly price data. In this paper, I discuss an alternative approach to constructing monthly proxies from daily surprises that takes account of this link and revisit the question of how to use OPEC announcements to identify news shocks in VAR models of the global oil market. The proposed approach calls into question the interpretation of the identified shock as oil supply news and implies quantitatively and qualitatively different estimates of the macroeconomic impact of OPEC announcements.

Changes in Soil Aggregate Carbon Components and Responses to Plant Input during Vegetation Restoration in the Loess Plateau, China.

Vegetation restoration is an effective measure to cope with global climate change and promote soil carbon sequestration. However, during vegetation restoration, the turnover and properties of carbon within various aggregates change. The effects of plant source carbon input on surface soil and subsurface soil may be different. Thus, the characteristics of carbon components in aggregates are affected. Therefore, the research object of this study is the Robinia pseudoacacia forest located in 16-47a of the Loess Plateau, and compared with farmland. The change characteristics of organic carbon functional groups in 0-20 cm, 20-40 cm, and 40-60 cm soil layers were analyzed by Fourier near infrared spectroscopy, and the relationship between the chemical structure of organic carbon and the content of organic carbon components in soil aggregates was clarified, and the mechanism affecting the distribution of organic carbon components in soil aggregates was revealed in the process of vegetation restoration. The results show the following: (1) The stability of surface aggregates is sensitive, while that of deep aggregates is weak. Vegetation restoration increased the surface soil organic carbon content by 1.97~3.78 g·kg-1. (2) After vegetation restoration, the relative contents of polysaccharide functional groups in >0.25 mm aggregates were significantly reduced, while the relative contents of aromatic and aliphatic functional groups of organic carbon were significantly increased. The opposite is true for aggregates smaller than 0.25 mm. (3) With the increase in soil depth, the effect of litter on organic carbon gradually decreased, while the effect of root input on the accumulation of inert carbon in deep soil was more lasting.

STABILIZATION MECHANISMS OF EU MONETARY POLICY IN THE CONTEXT OF INTERACTION WITH THE FINANCIAL SPHERE OF UKRAINE

Existing classic methods of analysing the monetary policy of the central bank, such as the aggregate response function, explain the behavior of the ECB in a rather simplified way. This is the result of the fact that classical methods do not consider the regional features of the members of the European Monetary Un ion and the structure of the system of central banks. The study of monetary policy with the involvement of macroeconomic theories of organization, theories of teams and coalition behavior, which are new for a macroeconomic subject, can make a significant contribution to the research process of European monetary integration. Since European integration is declared as a strategic direction of Ukraine’s economic development, the analysis and generalization of the problem of the modern European economy in the context of the impact of Russia’s war against Ukraine from 2022 is relevant. Therefore, in order to understand the problems and prospects of modernization of the functioning of the monetary and credit system in the EU, it is important to research and scientifically substantiate the stabilization mechanisms for Ukraine. The article investigates some stabilization mechanisms that are Ukraine Facility and Multi-Agency Donor Coordination Platform. Funding by Ukraine Facility is analysed through its pillars, components and implementation of main conditions for receiving benefits on the way of Ukrainian economy recovery. MultiAgency Donor Coordination Platform for Ukraine, as innovative instrument for coordinating activities of its members, is researched on the base of its existing funding mechanisms: the G7 Finance Track, the G7+ Coordination Group on energy infrastructure and the International Financial Institutions (IFIs) Coordination Group.

Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report.

Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined. Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released. Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] μmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4. Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.

Individual differences in perceived changes and impacts on well-being of working from home during the COVID-19 pandemic

This study examines how individual differences in employees' demographics, physical workspace, job satisfaction, workplace support, and pandemic-induced changes affected subjective well-being, productivity, and overall flourishing (Flourishing Index, FI) while working from home (WFH). A cohort of 602 employees in Bangkok, Thailand, was surveyed. Factor Analysis of Mixed Data (FAMD) revealed underlying interactions between variables that reflected differences in FI scores and work-related perceptions. In-person focus group interviews were conducted with 30 participants following their return to work to deepen understanding of aggregate survey responses. We found that the flourishing domains and short-term positive and negative affects are significantly influenced by satisfaction with the physical environment, demographics (e.g., age, marital status, and employment tier), and perceived changes in emotions, job demand, and resources. Individuals who enjoyed higher well-being ratings while WFH tended to be male, above 35 years old, in more senior employment positions, and married or living with a partner. Qualitative results confirmed how individual differences provided resilience and well-being under WFH while revealing more nuanced aspects of employer-employee support relevant to future personnel interventions. The variable groups also interact with each other, suggesting potential scenarios where individuals and organizations can implement more targeted interventions, such as physical environmental comfort, work-life balance, and social system support in future WFH situations to sustain employees’ well-being. It also shows that flourishing can be used as an indicator of worker well-being that reflects many nuanced life aspects, offering a new management tool for workplace transitions to WFH and hybrid models.

Analysis of the effect of aggregate type on the dynamic behaviour of concrete

This paper focuses on how different aggregate types affect the dynamic response of concrete. While Split Hopkinson Pressure Bar (SHPB) is commonly used to assess dynamic behaviour through the dynamic increase factor (DIF), the specific influence of aggregate type, a major component of concrete, remains unclear. This influence is investigated using fast Fourier transform analysis of strain signals. Two different types of aggregates, sandstone and schist, with distinct geological origins and mineral compositions, are used to examine this effect. Energy analysis is performed to understand how aggregate type affects energy absorption. The fineness modulus of fractured specimens is also determined which allow the comparison of post-fracture grain sizes. A crucial link between aggregate type and dynamic response of concrete is observed. Stiffer aggregates lead to stiffer concrete, which influence the frequency of energy responsible for damage initiation. At lower strain rates, concrete with stiffer aggregates absorbs lower-frequency energy. However, as strain rate increases, the frequency of absorbed energy becomes more dependent on the extent of damage within the aggregates themselves. The type of aggregate also significantly affects the size distribution of the fractured material. To analyse the stress distribution under dynamic loading, numerical simulations are carried out. These simulations showed that the maximum stress in concrete is related to the stiffness of the aggregate.

A Platelet Reactivity ExpreSsion Score derived from patients with peripheral artery disease predicts cardiovascular risk

Platelets are key mediators of atherothrombosis, yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. In this study, we investigate the association of platelet hyperreactivity and cardiovascular events, and introduce a tool, the Platelet Reactivity ExpreSsion Score (PRESS), which integrates platelet aggregation responses and RNA sequencing. Among patients with peripheral artery disease (PAD), those with a hyperreactive platelet response (>60% aggregation) to 0.4 µM epinephrine had a higher incidence of the 30 day primary cardiovascular endpoint (37.2% vs. 15.3% in those without hyperreactivity, adjusted HR 2.76, 95% CI 1.5–5.1, p = 0.002). PRESS performs well in identifying a hyperreactive phenotype in patients with PAD (AUC [cross-validation] 0.81, 95% CI 0.68 –0.94, n = 84) and in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 –0.79, n = 35). Following multivariable adjustment, PAD individuals with a PRESS score above the median are at higher risk for a future cardiovascular event (adjusted HR 1.90, CI 1.07–3.36; p = 0.027, n = 129, NCT02106429). This study derives and validates the ability of PRESS to discriminate platelet hyperreactivity and identify those at increased cardiovascular risk. Future studies in a larger independent cohort are warranted for further validation. The development of a platelet reactivity expression score opens the possibility for a personalized approach to antithrombotic therapy for cardiovascular risk reduction.