Search Results (44)

Behavior change technologies are increasingly deployed in everyday contexts where perception errors are difficult to avoid. Such errors can undermine user trust and long-term engagement, while purely technical approaches to error elimination are often impractical in open-world environments. This study proposes a fault-tolerant design that translates algorithmic uncertainty into anthropomorphic expressions of vulnerability. By decoupling task-outcome feedback from internal confidence states, an embodied agent communicates uncertainty through a five-level nonverbal framework comprising posture, facial expression, and motion intensity. The approach was implemented in an interactive waste-sorting system and examined through a three-week field study in a semi-public university corridor. Three feedback strategies were compared: an outcome-only baseline, a persistently confident agent, and an adaptive agent whose vulnerability expression varied according to a transformed confidence signal. The findings suggest differences in user behavior across conditions. Under the adaptive condition, user sorting accuracy exhibited a fluctuation–recovery pattern during the final deployment phase, whereas accuracy under the confident-agent condition showed a declining trend. Correct-trial stay durations were shorter under the adaptive condition, consistent with the formation of a more streamlined interaction routine. In contrast, observations from error cases were limited by the small number of misclassification events. Due to the exploratory nature of the study, the small sample size of the questionnaire and the sequential deployment structure, the results should be considered preliminary evidence. Nevertheless, the findings suggest that expressing vulnerability in an anthropomorphic way may be a promising approach for communicating uncertainty in behavior change systems. Full article

This study proposes a theoretical–empirical framework for analyzing political regimes based on a structural analogy between electoral behavior and spin-glass systems in statistical physics. Society is modeled as a system of interacting agents (voters) influenced by both interpersonal interactions and external factors such as media and institutions, formalized through a social Hamiltonian. By introducing a partition function and free energy, political regimes are interpreted as distinct macroscopic phases governed by four effective macro-parameters: external field, conformism, interaction heterogeneity, and inverse social temperature. Democratic societies correspond to a multistable regime characterized by sensitivity to initial conditions and replica symmetry breaking (RSB), reflecting the coexistence of competing social configurations. Authoritarian regimes, in contrast, arise when a strong unidirectional external field, high conformism, and low effective social temperature stabilize a single dominant macroscopic state, producing a regime analogous to replica symmetry (RS). A central result of the model is the distinction between the predictability of macroscopic outcomes and structural social multistability, as well as between natural and externally imposed homogenization of collective behavior. To illustrate the empirical relevance of the framework, the model is applied to the transition from the Weimar Republic to the National Socialist regime (1919–1933), using aggregated electoral data to construct proxy indicators for the effective parameters governing social interactions. The proposed approach enables structural identification of early signals of authoritarian transition through changes in the parameters of social dynamics. Full article

Even when people with diabetes mellitus (DM) meet their cholesterol goals, they still face a higher risk of heart and blood vessel problems. One major reason is a particle called lipoprotein(a), or Lp(a), which is similar to LDL cholesterol. Raised levels of Lp(a) are inherited rather than caused by lifestyle. Lp(a) can build up in the body and make it easier for blood clots to form because it closely resembles a protein called plasminogen, reducing its ability to form plasmin that dissolves blood clots. At the same time, chemical changes like oxidation and glycation can make blood vessels more inflamed, adding to the risk. Elevated concentrations of Lp(a) (>30 mg/dL; 75 nmol/L), and particularly >50 mg/dL (125 nmol/L), are independently associated with coronary artery disease, ischemic stroke, diabetic nephropathy, retinopathy, and neuropathy. Conventional lipid-lowering therapies exert neutral or modest effects on Lp(a), in contrast to RNA-based targeted agents (antisense oligonucleotides and siRNA [Small Interfering RNA]), which achieve reductions of 70–95% and show consistent results in Phase 2 clinical trials. In this review, we bring together findings from laboratory research and clinical studies, and highlight why it is important to measure Lp(a) levels—at least once in a person’s life, and especially in those with diabetes—to help doctors better assess risk and plan more effective treatments. In diabetic populations, the adaptation of Lp(a)-targeted therapies could redefine the management of residual risk and improve both cardiovascular and microvascular outcomes. Full article

Background/Objectives: Targeted cancer therapies increasingly rely on modulating specific cell death pathways and kinase signaling. Due to their structural versatility and potential to induce mechanistically distinct cytotoxic responses, benzoxazine–purine hybrids represent a promising scaffold for anticancer drug development. The objective of this study was to design and evaluate novel benzoxazine–purine derivatives for their antiproliferative activity and elucidate their underlying mechanisms of action. Methods: A series of benzoxazine–purine compounds was synthesized via a modular and efficient approach. The synthetic route involved a one-pot cyclization of substituted 2-aminophenols with epichlorohydrin, followed by tosylation and subsequent Mitsunobu coupling with halogenated purines. Their antiproliferative activity was assessed in MCF-7 (breast) and HCT-116 (colon) cancer cell lines using MTT assays. Selected compounds were evaluated further for kinase inhibition, effects on the cell cycle, membrane integrity (Annexin V/PI staining), ultrastructural changes (SEM), and caspase activation (Western blot). In silico ADMET profiling was also performed. Results: Compounds 9 and 12 exhibited the most potent antiproliferative activity, with low micromolar IC₅₀ values. Compound 12 showed dual HER2/JNK1 kinase inhibition and induced caspase-8-dependent pyroptosis-like cell death, characterized by membrane rupture and inflammatory features. In contrast, compound 8 lacked kinase inhibition and promoted S-phase arrest with apoptotic-like morphology. Both compounds demonstrated favorable physicochemical and ADMET profiles, including high intestinal absorption and an absence of mutagenicity. Conclusions: The rational design of benzoxazine–purine hybrids resulted in the discovery of compounds with distinct mechanisms of action. Compound 12 induces inflammatory cell death by modulating kinases, while compound 9 acts through a kinase-independent apoptotic pathway. These results underscore the therapeutic potential of scaffold-based diversification for developing targeted anticancer agents. Full article

Recently, the development of nanoparticle pigments has attracted interest in chemical preparation due to their potential functional properties, such as phosphate-based pigments. The present research focuses on the feasibility of synthesising the BaCr₂(P₂O₇)₂ pigment under hydrothermal conditions. The effect of the microstructural features of ceramic pigments (the crystalline structure, morphology, and particle size) on their optical properties (colour and reflectance) was also studied. The BaCr₂(P₂O₇)₂ compound was prepared in different fluid media, including water and NaOH solutions (0.5–1.0 M), at several reaction temperatures (170–240 °C) and intervals (6–48 h). The single-phase BaCr₂(P₂O₇)₂ did not crystallise without by-products (BaCr₂O₁₀, BaCr₂(PO₇)₂) in water and the alkaline solutions, even at 240 °C for 48 h; in these fluids, the ionic Cr³⁺ species oxidised to Cr⁶⁺. In contrast, the BaCr₂(P₂O₇)₂ single-phase crystallisation was favoured by adding urea as a reductant agent (25.0–300.0 mmol). Monodispersed BaCr₂(P₂O₇)₂ fine particles with a mean size of 44.0 nm were synthesised at a low temperature of 170 °C for 6 h with 0.5 M NaOH solution in the presence of 50.0 mmol urea. The phosphate pigment particle grew to approximately 62.0 nm by increasing the treatment temperature to 240 °C. A secondary dissolution–recrystallisation achieved after 24 h triggered a change in the particle morphology coupled with the incrementation of the concentration of NaOH in the solution. The pyrophosphate BaCr₂(P₂O₇)₂ pigments prepared in this study belong to the green colour spectral space according to the CIELab coordinates measurement, and exhibit 67.5% high near-infrared (NIR) solar reflectance. Full article

Background: Tracheal intubation and mechanical ventilation are facilitated by neuromuscular blocking agents. We investigated the effectiveness of subjective clinical evaluation of neuromuscular function on retroglossal area size, since it determines spontaneous ventilation adequacy following tracheal extubation. Secondarily, we correlated changes in retroglossal area and depth of neuromuscular block assessed during both respiratory phases using quantitative neuromuscular monitoring. Methods: Once mechanical ventilation was no longer needed, antagonists were used to reverse the neuromuscular block in 21 consenting patients; adequacy of reversal was assessed subjectively by delivering a sequence of four rapid (2 Hz) electrical stimuli (train-of-four, TOF) to a peripheral nerve and assessing attainment of four equal muscle contractions (TOF ratio = 1.0), signifying normal neuromuscular function. Retroglossal area during both inhalation and exhalation were measured pharyngoscopically at various phases of neuromuscular recovery, including at baseline after anesthesia induction but before neuromuscular block onset and at recovery before tracheal extubation; area changes were correlated with depth of quantitatively measured neuromuscular block. Results: Clinicians’ subjective evaluation of readiness for tracheal extubation failed to identify significant residual block in most patients who required rescue antagonism. Markedly decreased retroglossal areas (inhalation: 39.5% of baseline; exhalation: 20.1% of baseline) were present at extubation, and 11 out of 21 (52.4%) patients needed rescue antagonism. In contrast, in patients with neuromuscular recovery to the currently recommended threshold determined quantitatively (TOF ratio > 0.90), retroglossal areas were only 80% recovered but returned to near baseline values when the TOF ratio ≥ 0.95. Conclusions: Quantitative monitoring should guide the timing of tracheal extubation. Current definitions of the minimal threshold for adequate neuromuscular recovery (TOF ratio > 0.90) after mechanical ventilation in postoperative patients should be re-evaluated. A TOF ratio > 0.95 better correlates with return to normal (baseline) retroglossal area during both inhalation and exhalation. Full article

Background: When plotting data points corresponding to the contrast-agent-induced change in transverse relaxation rate from a dynamic gradient-echo (GRE) magnetic resonance imaging (MRI) study versus a corresponding spin-echo study, a loop or vortex curve rather than a reversible line is formed. The vortex curve area is likely to reflect vessel architecture and oxygenation level. In this study, the vortex effect seen when using only GRE-based estimates, i.e., contrast-agent concentration based on GRE transverse relaxation rate and contrast-agent concentration based on quantitative susceptibility mapping (QSM), was investigated. Methods: Twenty healthy volunteers were examined using 3 T MRI. Magnitude and phase dynamic contrast-enhanced MRI (DSC-MRI) data were obtained using GRE echo-planar imaging. Vortex curves for grey-matter (GM) regions and for arterial input function (AIF) data were constructed by plotting concentration based on GRE transverse relaxation rate versus concentration based on QSM. Vortex parameters (vortex area and normalised vortex width) were compared with QSM-based whole-brain OEF estimates obtained using 3D GRE. Results: An obvious vortex effect was observed, and both GM vortex parameters showed a moderate and significant correlation with OEF (r = −0.51, p = 0.02). The vortex parameters for AIF data showed no significant correlation with OEF. Conclusions: GRE-based GM vortex parameters correlated significantly with whole-brain OEF. In agreement with expectations, the corresponding AIF data, representing high fractions of arterial blood, showed no significant correlation. Novel parameters, based solely on standard GRE protocols, are of relevance to investigate, considering that GRE-based DSC-MRI is very common in brain tumour applications. Full article

This research examines the possibility of the washing process as a supplementary operation after extensive extended physical separation sequences for processed incinerator bottom ash (pr.IBA), which is the mineral fraction resulting from conventional separation operation of municipal solid waste (MSW) incinerator bottom ash (IBA) in Germany. Citric acid is employed as the only primary treatment agent in several variations of parameter combinations. It includes the type of solvent, washing duration, acid concentration, liquid-to-solid ratio, and introduction of external agitation (stirring and heating). The analysis results revealed that the concentration of copper, zinc, and manganese in the mineral phase of pr.IBA can be reduced by the citric acid washing process. The most significant change is observed in the zinc content, where a reduction of up to 50% is successfully achieved. In contrast, the silicon concentration is relatively unaffected during citric acid washing, but a concentration decrease is detected for calcium. The aluminum and iron contents in the studied fraction of pr.IBA are also soluble in citric acid solution, although the rates are expected to be exceptionally slow. In this instance, stirring and heating over a prolonged washing duration are necessary before a decrease in their concentration can eventually occur. Full article

The demand for advanced Al-based alloys with tailored structural and magnetic properties has intensified for applications requiring a high thermal stability and performance under challenging conditions. This study investigated the phase evolution, magnetic properties, thermal stability, and microstructural changes in the Al-based alloys Al₈₂Fe₁₆Nb₂ and Al₈₂Fe₁₄Nb₂Mn₂, synthesized via mechanical alloying (MA), using stearic acid as a process control agent. The X-ray diffraction results indicated that Al₈₂Fe₁₆Nb₂ achieved a β-phase solid solution with 13–14 nm crystallite sizes after 5 h of milling, reaching an amorphous state after 10 h. In contrast, Al₈₂Fe₁₄Nb₂Mn₂ formed a partially amorphous structure within 10 h, with enhanced stability with additional milling. Magnetic measurements indicated that both alloys possessed soft magnetic behavior under shorter milling times (1–5 h) and transitioned to hard magnetic behavior as amorphization progressed. This phenomenon was associated with a decrease in saturation magnetization (M_s) and an increase in coercivity (H_c) due to structural disorder and residual stresses. Thermal stability analyses on 10 h milled samples conducted via differential scanning calorimetry showed exothermic peaks between 300 and 800 °C, corresponding to phase transformations upon heating. Post-annealing analyses at 550 °C demonstrated the presence of phases including Al, β-phase solid solutions, Al₁₃Fe₄, and residual amorphous regions. At 600 °C, the Al₃Nb phase emerged as the β-phase, and the amorphous content decreased, while annealing at 700 °C fully decomposed the amorphous phases into stable crystalline forms. Microstructural analyses demonstrated a consistent reduction in and homogenization of particle sizes, with particles decreasing to 1–3 μm in diameter after 10 h. Altogether, these findings highlight MA’s effectiveness in tuning the microstructure and magnetic properties of Al–Fe–Nb (Mn) alloys, making these materials suitable for applications requiring a high thermal stability and tailored magnetic responses. Full article

In the transition to sustainable energy consumption, waste heat recovery and storage systems become key to advancing Europe’s energy efficiency and reducing carbon emissions, especially by harnessing thermal energy from low-temperature sources like wastewater. This study focuses on optimizing a heat recovery system that uses heat pipes for effective heat extraction and coconut oil as a phase change material for efficient thermal storage. A total of 12 numerical simulations were conducted to analyze the outcomes of varying operational parameters, including the diameter of the heat pipe, condenser size, secondary agent flow rate, coil length, and primary agent inlet temperature. The numerical findings indicate that reduced flow rates, in combination with smaller condenser diameters and increased primary agent temperatures, greatly improve the efficiency of heat absorption and transfer. Following a 4 h test period, the most successful outcome resulted in a melting fraction of 98.8% and a temperature increase of 18.95 °C in the output temperature of the secondary agent. In contrast, suboptimal conditions resulted in only a 2.21 °C rise and a 30.80% melting fraction. The study highlights the importance of component sizing and optimization, noting that strategic modifications and appropriate phase change materials can lead to highly efficient and scalable systems. Full article

Radiotherapy treatment plans have become highly conformal, posing additional constraints on the accuracy of treatment delivery. Here, we explore the use of radiation-sensitive ultrasound contrast agents (superheated phase-change nanodroplets) as dosimetric radiation sensors. In a series of experiments, we irradiated perfluorobutane nanodroplets dispersed in gel phantoms at various temperatures and assessed the radiation-induced nanodroplet vaporization events using offline or online ultrasound imaging. At 25 °C and 37 °C, the nanodroplet response was only present at higher photon energies (≥10 MV) and limited to <2 vaporization events per cm² per Gy. A strong response (~2000 vaporizations per cm² per Gy) was observed at 65 °C, suggesting radiation-induced nucleation of the droplet core at a sufficiently high degree of superheat. These results emphasize the need for alternative nanodroplet formulations, with a more volatile perfluorocarbon core, to enable in vivo photon dosimetry. The current nanodroplet formulation carries potential as an innovative gel dosimeter if an appropriate gel matrix can be found to ensure reproducibility. Eventually, the proposed technology might unlock unprecedented temporal and spatial resolution in image-based dosimetry, thanks to the combination of high-frame-rate ultrasound imaging and the detection of individual vaporization events, thereby addressing some of the burning challenges of new radiotherapy innovations. Full article

The present study examined the hypothesis that changes in the oxidation–reduction state of thiol residues in functional proteins play a major role in the expression of the ventilatory responses in conscious rats that occur during a hypoxic–hypercapnic (HH) gas challenge and upon return to room air. A HH gas challenge in vehicle-treated rats elicited robust and sustained increases in minute volume (via increases in frequency of breathing and tidal volume), peak inspiratory and expiratory flows, and inspiratory and expiratory drives while minimally affecting the non-eupneic breathing index (NEBI). The HH-induced increases in these parameters, except for frequency of breathing, were substantially diminished in rats pre-treated with the potent and lipophilic disulfide-reducing agent, L,D-dithiothreitol (100 µmol/kg, IV). The ventilatory responses that occurred upon return to room air were also substantially different in dithiothreitol-treated rats. In contrast, pre-treatment with a substantially higher dose (500 µmol/kg, IV) of the lipophilic congener of the monosulfide, N-acetyl-L-cysteine methyl ester (L-NACme), only minimally affected the expression of the above-mentioned ventilatory responses that occurred during the HH gas challenge or upon return to room air. The effectiveness of dithiothreitol suggests that the oxidation of thiol residues occurs during exposure to a HH gas challenge and that this process plays an essential role in allowing for the expression of the post-HH excitatory phase in breathing. However, this interpretation is contradicted by the lack of effects of L-NACme. This apparent conundrum may be explained by the disulfide structure affording unique functional properties to dithiothreitol in comparison to monosulfides. More specifically, the disulfide structure may give dithiothreitol the ability to alter the conformational state of functional proteins while transferring electrons. It is also possible that dithiothreitol is simply a more efficient reducing agent following systemic injection, although one interpretation of the data is that the effects of dithiothreitol are not due to its reducing ability. Full article

To assess the impact of first-line treatment with targeted agents (TAs) or fludarabine, cyclophosphamide, and rituximab (FCR)-based chemo-immunotherapy (CIT) on overall survival (OS) compared to age- and sex-matched individuals in the general population, we conducted an aggregated analysis of phase 3 clinical trials, including the two FLAIR sub-studies, ECOG1912, and CLL13 trials. The restricted mean survival time (RMST), an alternative measure in outcome analyses capturing OS changes over the entire history of the disease, was used to minimize biases associated with the short follow-up time of trials. Patients treated with TAs demonstrated a higher 5-year RMST (58.1 months; 95% CI: 57.4 to 58.8) compared to those treated with CIT (5-year RMST, 56.9 months; 95% CI: 56.7–58.2). Furthermore, the OS comparison of treatment groups with the AGMGP suggests that TAs may mitigate the impact of CLL on OS during the first five years post-treatment initiation. In summary, the 5-year RMST difference was −0.4 months (95% CI: −0.8 to 0.2; p = 0.10) when comparing CLL patients treated with TAs to the Italian age- and gender-matched general population (AGMGP). A similar trend was observed when CLL patients treated with TAs were compared to the US AGMGP (5-year RMST difference, 0.3 months; 95% CI: −0.1 to 0.9; p = 0.12). In contrast, CLL patients treated with FCR exhibited sustained OS differences when compared to both the Italian cohort (5-year RMST difference: −1.6 months; 95% CI: −2.4 to −0.9; p < 0.0001) and the US AGMGP cohort (5-year RMST difference: −0.9 months; 95% CI: −1.7 to −0.2; p = 0.015). Although these results support TAs as the preferred first-line treatment for younger CLL patients, it is crucial to acknowledge that variations in patient selection criteria and clinical profiles across clinical trials necessitate a cautious interpretation of these findings that should be viewed as directional and hypothesis-generating. A longer follow-up is needed to assess the survival improvement of younger CLL patients treated with TAs relative to the AGMGP. Full article

There is an evolving landscape of systemic combination regimens for patients with advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In this review, we provide a comprehensive outline of the existing clinical trials/prospective studies investigating these combinations. PubMed was searched using key relevant terms to identify articles referring to GEP-NETs and combination treatments. No systematic search of the literature or metanalysis of the data was performed, and we focused on the most recent literature results. Primarily, phase 1 and 2 clinical trials were available, with a smaller number of phase 3 trials, reporting results from combination treatments across a wide range of antiproliferative agents. We identified significant variability in the anti-tumor activity of the reported combinations, with occasional promising results, but only a very small number of practice-changing phase 3 clinical trials. Overall, the peptide receptor radionuclide therapy (PRRT)-based combinations (with chemotherapy, dual PPRT, and targeted agents) and anti-vascular endothelial growth factor (VEGF) agent combinations with standard chemotherapy were found to have favorable results and may be worth investigating in future, larger-scale trials. In contrast, the immune-checkpoint inhibitor-based combinations were found to have limited applicability in advanced, well-differentiated GEP-NETs. Full article

Magnetic hybrid hydrogels have exhibited remarkable efficacy in various areas, particularly in the biomedical sciences, where these inventive substances exhibit intriguing prospects for controlled drug delivery, tissue engineering, magnetic separation, MRI contrast agents, hyperthermia, and thermal ablation. Additionally, droplet-based microfluidic technology enables the fabrication of microgels possessing monodisperse characteristics and controlled morphological shapes. Here, alginate microgels containing citrated magnetic nanoparticles (MNPs) were produced by a microfluidic flow-focusing system. Superparamagnetic magnetite nanoparticles with an average size of 29.1 ± 2.5 nm and saturation magnetization of 66.92 emu/g were synthesized via the co-precipitation method. The hydrodynamic size of MNPs was changed from 142 nm to 826.7 nm after the citrate group’s attachment led to an increase in dispersion and the stability of the aqueous phase. A microfluidic flow-focusing chip was designed, and the mold was 3D printed by stereo lithographic technology. Depending on inlet fluid rates, monodisperse and polydisperse microgels in the range of 20–120 μm were produced. Different conditions of droplet generation in the microfluidic device (break-up) were discussed considering the model of rate-of-flow-controlled-breakup (squeezing). Practically, this study indicates guidelines for generating droplets with a predetermined size and polydispersity from liquids with well-defined macroscopic properties, utilizing a microfluidic flow-focusing device (MFFD). Fourier transform infrared spectrometer (FT-IR) results indicated a chemical attachment of citrate groups on MNPs and the existence of MNPs in the hydrogels. Magnetic hydrogel proliferation assay after 72 h showed a better rate of cell growth in comparison to the control group (p = 0.042). Full article