Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such data for first-line ICI therapy and especially for chemotherapy-ICI combinations are still scarce, we retrospectively evaluated baseline 18F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n=70) or as monotherapy (n=15). Maximum and mean standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis and bone marrow-/ spleen to liver ratio (BLR/SLR) were calculated. Kaplan-Meier analyses and Cox-regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p<0.001). Median PFS/OS were significantly longer in patients with MTV≤70mL versus >70mL (PFS: 10 months (M; 95% confidence interval 4-16) vs. 4M (3-5), p=0.001; OS: not reached vs. 10M (5-15), p=0.004). Disease control rate was 81% vs. 53% for MTV≤/>70mL (p=0.007). BLR ≤1.06 versus >1.06 was associated with better outcomes (PFS: 8M (4-13) vs. 4M (3-6), p=0.034; OS: 19M (12-/) vs. 6M (4-12), p=0.005). In patients with MTV>70mL, concomitant BLR≤1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI treated NSCLC, with BLR allowing additional risk stratification.

We consider a family of nonlinear singularly perturbed PDEs whose coefficients involve a logarithmic dependence in time with confluent Fuchsian singularities that unfold an irregular singularity at the origin and rely on a single perturbation parameter. We exhibit two distinguished finite sets of holomorphic solutions, so-called outer and inner solutions, by means of a Laplace transform with special kernel and Fourier integral. We analyze the asymptotic expansions of these solutions relatively to the perturbation parameter and show that they are (at most) of Gevrey order 1 for the first set of solutions and of some Gevrey order that hinges on the unfolding of the irregular singularity for the second.

While human activities and climate change are threatening available natural ecosystems, targeted studies on the biological cycle, propagation, and cultivation of threatened species are crucial both for their conservation and sustainable exploitation. This study was designed to bridge extant research gaps regarding the vulnerable local endemic Campanula pelviformis, a wild edible green traditionally consumed in Crete (Greece) with agro-alimentary and medicinal interest as well as ornamental value. New knowledge was obtained on the abiotic environmental conditions prevailing in its wild habitats (natural distribution mapped in Geographical Information Systems and linked with open-source databases). We collected seeds from wild-growing populations (three lowland, two semi-mountainous), we tested their germination at four different temperatures (10, 15, 20 and 25oC) and under different light conditions (light/dark and darkness), and we performed fertilization trails [integrated nutrient management (INF), chemical fertilization (ChF), control] examining morphological and physiological characteristics, above- and below-ground macro- and micronutrients contents, as well as their phenol content and antioxidant capacity. There were population and temperature effects on seed germination and their interaction was statistically significant. Campanula pelviformis germinated better at 10 and 15 oC (&gt;85% for all populations) with no preference on light conditions (98.75% and 95% in light and dark conditions). The INF application increased root dry mass, chlorophyll content index and chlorophyll fluorescence compared to other treatments and was beneficial for macro- and micronutrients concentrations in above-ground parts compared to previously studied wild-growing material, while below-ground parts were positively impacted by both fertilization types. Total phenols and antioxidant capacity were both increased by ChF fertilization. The data furnished herein led to the re-evaluation and upgrade of the feasibility and the readiness timescale for its sustainable exploitation in different economic sectors.

In this paper, we study nonlocal problems for a fractional diffusion equation and a degenerate hyperbolic equation with singular coefficients in the lower terms. The uniqueness of the solution to the problem is proved by the method of energy integrals. The existence of a solution is equivalently reduced to the question of the solvability of Volterra integral equations of the second kind and a fractional differential equation. For a particular solution of the proposed problem, its visualization is carried out for various values of the order of the fractional derivative. It is shown that the order of the derivative affects the intensity of the diffusion process (subdiffusion), as well as the shape of the wave front.

Addressing the urgent sustainability challenges in the wine industry, this study explores the efficacy of sustainability-oriented innovations (SOIs) and smart farming technologies (SFTs) across wine value chains in Cyprus and Italy. Employing KPIs for a rigorous assessment, the research delves into the environmental, economic, and social impacts of these technologies. In Cyprus (SIP7), the integration of digital labelling and smart farming solutions led to a substantial reduction in pesticide usage by up to 75% and enhanced the perceived quality of wine by an average of 8%. Italy's SIP10 witnessed a 33.4% decrease in greenhouse gas emissions, with an additional benefit of a 5.3% improvement in intrinsic product quality. Notably, SIP10 also introduced a carbon credit system, potentially generating an average annual revenue of €4,140 per farm. These findings highlight the transformative potential of SOIs and SFTs in promoting sustainable practices within the wine industry, demonstrating significant advancements in reducing environmental impact, improving product quality, and enhancing economic viability. The study underscores the critical role of innovative technologies in achieving sustainability goals and provides a compelling case for wider adoption within the agricultural sector.

(1) In an era where sustainable behavior is increasingly crucial, understanding the discrepancy between individuals' sustainability-oriented values and their actual behaviors, known as the inner-outer gap, is vital. This study explores the potential of the Tripartite Structure of Sustainability (TSS) framework to address this gap within the context of sustainable education. By reviewing literature from the databases APA, ERIC, and Web of Science, we systematically examined factors influencing sustainable actions. (2) Employing a qualitative content analysis approach, we analyzed 56 articles over a 15-year period, identifying 83 factors that either bridge or reinforce the inner-outer gap. These factors were categorized within the TSS framework, which segments sustainability-oriented actions into individual, social, and self-transcendent domains, alongside their activation points: stable, situational, or automated. (3) Our analysis revealed that self-focused factors often reinforce the gap, suggesting a hindrance to sustainable behavior. Conversely, self-transcendent factors consistently bridged the gap, promoting sustainability. Social factors showed variable impacts based on the ethical and sustainable context they were placed in, suggesting that the social environment's orientation significantly influences sustainable behavior. (4) The study concludes that the TSS framework offers a promising approach to advancing sustainability in education by facilitating a paradigm shift towards holistic and interconnected perspectives. This shift is critical for fostering sustainable behaviors, thereby contributing to the field of educational psychology and offering practical implications for educators aiming to nurture a sustainable future.

Large values and gradients of stresses and deformations, triggering concentrations of stresses and deformations, arise in the corner areas of a structure. The action of forced deformations, leading to the finite rupture of the contact between the elements of a structure, also triggers the concentration of stresses, while the rupture reaches an irregular point, a line on the area boundary. The theoretical analysis of the stress-strain state (SSS) of areas with angular cutouts in the boundary under the action of discontinuous forced deformations is reduced to the study of singular solutions to the homogeneous problem of the elasticity theory that has power-related features. The calculation of stress concentration coefficients in the domain of a singular solution to the elastic problem makes no sense. It is experimentally proven that the zone, that is close to the vertex of the angular cutout in the area boundary, has substantial deformations, rotations, and it corresponds to rising values of the first and second derivatives of displacements along the radius in cases of sufficiently small radii in the neighbourhood of the irregular point of the boundary. For such areas, it is necessary to consider the plane problem of the elasticity theory, taking into account the geometric nonlinearity under the action of forced deformations. This will allow analyzing the effect of relations between orders of values of deformations, rotations, and forced deformations on the form of the equation of equilibrium. The purpose of this work is to analyze the effect of relations of deformation orders, rotations, forced deformations on the form of the equilibrium equation in the polar coordinate system for a V-shaped area under the action of forced temperature-induced deformations with regard for the geometrical non-linearity and physical linearity.

In the face of the upcoming 30th anniversary of econophysics, we review our contributions and other related works on the modeling of the long–range memory phenomenon in physical, economic, and other social complex systems. Our group has shown that the long–range memory phenomenon can be reproduced using various Markov processes, such as point processes, stochastic differential equations and agent–based models. Reproduced well enough to match other statistical properties of the financial markets, such as return and trading activity distributions and first–passage time distributions. Research has lead us to question whether the observed long–range memory is a result of actual long–range memory process or just a consequence of non–linearity of Markov processes. As our most recent result we discuss the long–range memory of the order flow data in the financial markets and other social systems from the perspective of the fractional Lèvy stable motion. We test widely used long-range memory estimators on discrete fractional Lèvy stable motion represented by the ARFIMA sample series. Our newly obtained results seem indicate that new estimators of self–similarity and long–range memory for analyzing systems with non–Gaussian distributions have to be developed.

Goals: To use visual logistics for interpreting COVID-19 molecular and rapid antigen test (RAgT) performance, determine prevalence boundaries where risk exceeds expectations, and evaluate benefits of recursive testing along home, community, and emergency spatial care paths. Methods: Mathematica/open access software helped graph relationships, compare performance patterns, and perform recursive computations. Results: Tiered sensitivity/specificity comprise: T1) 90%/95%; T2) 95%/97.5%; and T3) 100%/≥99%, respectively. In emergency medicine, median RAgT performance peaks at 13.2% prevalence, then falls below T1, generating risky prevalence boundaries. RAgTs in pediatric ERs/EDs parallel this pattern with asymptomatic worse than symptomatic performance. In communities, RAgTs display large uncertainty with median prevalence boundary of 14.8% for 1/20 missed diagnoses, and at prevalence >33.3-36.9% risk 10% false omissions for symptomatic subjects. Recursive testing improves home RAgT performance. Home molecular tests elevate performance above T1, but lack adequate validation. Conclusions: Widespread RAgT availability encourages self-testing. Asymptomatic RAgT and PCR-based saliva testing present the highest chance of missed diagnoses. Home testing twice, once just before mingling, and molecular-based self-testing help avoid false omissions. Community and ER/ED RAgTs can identify contagiousness in low prevalence (<22%). Real-world trials of performance, cost-effectiveness, and public health impact could identify home molecular diagnostics as the optimal diagnostic portal.

We introduce the Transformation Flower Approach (TFA), a Theory of Change that attends to multiple value creation and institutional change as a dual design challenge. We highlight how the TFA integrates social scientific theories and models relevant for transformative change (in particular focusing on pathways, leverage points, governance, power, and values) and demonstrate its practical value by an application to the ongoing transformation of the Dutch food system. By providing a holistic, transdisciplinary and practically relevant approach that aims to support new social contract formation, the TFA goes beyond other transformative change approaches. Based on the notion of pathways, it offers a toolbox that aids in working towards desired futures, involving both incumbents and challengers in an effort to harness untapped yet proximal potentials in a forward-looking way. By embracing an innovation approach, it not only promises to circumvent resistance to change, but also serves as a step-by-step approach to identify options for multiple value creation and effective cooperation. We demonstrate the analytical and practical value of the TFA by discussing action perspectives at various levels and scales in the context of the Dutch food system transition, including (1) area-oriented approaches, (2) acceleration agendas for specific transformation pathways, and (3) actor-specific transformation flowers. In developing these, we emphasize the importance of interdependencies between leverage points. Our approach helps to identify opportunities to link transformative options (the what), actors (the who) and levers (the how) in dynamic interaction to embark on transformative pathways.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.