Search Results (20,005)

Background: Pancreatic cancer (PC) and colorectal cancer (CRC) are among the most lethal malignancies, with growing evidence pointing to the gut microbiota’s role in their progression. This study aimed to explore the anticancer potential of two microbiota-derived postbiotics, N-acetylcysteine (NAC) and tetrahydro β-carboline carboxylic acid (THC), in targeting some hallmark traits of PC and CRC, both as standalone agents and in combination with standard chemotherapeutics (gemcitabine for PC and 5-fluorouracil (5-FU) for CRC). Methods: Cell viability assays and IC₅₀ determination was assessed using either the Muse™ Count & Viability Kit or the Sulforhodamine B assay; cell death was determined by Annexin V/Propidium Iodide and cell cycle assessed by Propidium Iodide was analyzed by flow cytometry. Results: Here, we found that NAC selectively reduced the viability of PC cells BxPC-3 without triggering apoptosis, while effectively inducing apoptosis in PC cells Panc-1 and in CRC cell lines. THC exhibited stronger anticancer activity, inhibiting proliferation and promoting apoptosis in all tested PC and CRC cells, even at lower concentrations. Combination treatments yielded promising enhancement effects. NAC enhanced the cytotoxicity of gemcitabine in Panc-1 cells through increased apoptosis. NAC, when combined with 5-FU, also increased apoptosis of CRC cells. THC further potentiated gemcitabine’s impact on Panc-1 cells by increasing apoptosis and by inducing cell cycle changes in BxPC-3. In the CRC model, THC co-treatment with 5-FU reduced cell viability and increased apoptosis in all cells. Conclusions: These findings provide preliminary in vitro evidence supporting the potential of integrating microbiota-derived postbiotics with conventional chemotherapy both in PC and CRC. Full article

Dynamic contrast-enhancement (DCE) modality of MRI is typically considered secondary in prostate cancer (PCa) diagnostics, due to the common interpretation that its diagnostic power is lower than that of other modalities like T2-weighted (T2W) or diffusion-weighted imaging (DWI). To challenge this paradigm, this study introduces a novel concept of a difference map, which relies exclusively on DCE-MRI for the localization of peripheral zone prostate cancer using functional data analysis-based (FDA) signal processing. The proposed workflow uses discrete voxel-level DCE time–signal curves that are transformed into a continuous functional form. First-order derivatives are then used to determine patient-specific time points of greatest enhancement change that adapt to the intrinsic characteristics of each patient, producing diffmaps that highlight regions with pronounced enhancement dynamics, indicative of malignancy. A subsequent normalization step accounts for inter-patient variability, enabling consistent interpretation across subjects and probabilistic PCa localization. The approach is validated on a curated dataset of 20 patients. Evaluation of eight workflow variants is performed using weighted log loss, the best variant achieving a mean log loss of 0.578. This study demonstrates the feasibility and effectiveness of a single-modality, automated, and interpretable approach for peripheral prostate cancer localization based solely on DCE-MRI. Full article

Background: Pulmonary infarction (PI) is the result of the occlusion of distal pulmonary arteries resulting in damage to downstream lung areas that become ischemic, hemorrhagic, or necrotic, and it is often a complication of an underlying condition such as pulmonary embolism (PE). Since in most of cases it is located peripherally, lung ultrasound (LUS) can be a good evaluation tool. The typical radiological features of PI are well-known; however, there are limited data on its sonographic characteristics and its evolution. Methods: The aim of this study is to evaluate, using LUS, a convenience sample of patients with acute PE with computed tomography (CT) consolidation findings consistent with PI. Patients’ clinical characteristics were collected and LUS findings at baseline and their short-term progression was assessed. LUS was performed within 72 h of PE diagnosis (T0) and repeated after one (T1) and four weeks (T2). Each procedure started with a focused examination of the areas of lesions based on CT findings, followed by an exploration of the other posterior and lateral lung fields. The convex probe was used for initial evaluation integrating LUS evaluation with the linear one was employed for smaller and more superficial lesions and when appropriate. Color Doppler mode was added to study vascularization. Results: From June to October 2023, 14 consecutive patients were enrolled at the Respiratory Unit of the University Hospital of Pisa. The main population characteristics included the absence of respiratory failure and prognostic high-risk PE (100%), the absence of significant comorbidities (79%), and the presence of typical symptoms, such as chest pain (57%) and dyspnea (50%). The average number of consolidations per patient was 1.4 ± 0.6. Follow-up LUS showed the disappearance of some consolidations and some morphological changes in the remaining lesions: the presence of hypoechoic consolidation with a central hyperechoic area (“bubbly consolidation”) was more typical at T1 while the presence of a small pleural effusion often persisted both at T1 and T2. A decrease in wedge/triangular-shaped consolidations was observed (82% at T0, 67% at T1, 24% at T2), as was an increase in elongated shapes, representing a residual pleural thickening over time (9% at T0, 13% at T1, 44% at T2). A reduction in size was also observed by comparing the mean diameter, long axis, and short axis measurements of each consolidation at the three different studied time points: the average of the short axes and the median of the mean diameters showed a statistically significant reduction after four weeks. Additionally, a correlation between lesion size and pleuritic pain was described, although it did not achieve statistical significance. Conclusions: Patients’ clinical characteristics and ultrasound features are consistent with previous studies studying PI at PE diagnosis. Most consolidations detected by LUS change over time regarding size and form, but a minority of them do not differ. LUS is a safe and non-invasive exam that could help to improve patients’ clinical approach in emergency rooms as well as medical and pulmonology settings, clinically contextualized for cases of chest pain and dyspnea. Future studies could expand the morphological study of PI. Full article

Background: Sleep is a key determinant of recovery and performance in elite athletes, yet its optimization extends beyond sleep duration alone and encompasses multiple subjective and physiological dimensions. Environmental factors, including the sleep surface, represent modifiable components of sleep that may influence perceived sleep quality. This study aimed to examine whether an individually adjustable modular sleep system improves subjective sleep quality in elite athletes and whether alterations in objective sleep metrics, circadian timing, or nocturnal autonomic physiology accompany such changes. Methods: Forty-three elite athletes participated in this pre–post-intervention study (without a control group). Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), while objective sleep and physiological parameters were recorded using a wearable device (Oura Ring, 3rd generation). Outcomes were averaged across three consecutive nights at baseline (T0) and post-intervention (T1). Baseline values were derived from the final three nights of a standardized pre-intervention monitoring period (minimum 7 nights), and post-intervention values from the final three nights following a standardized intervention exposure period (minimum 14 nights). Statistical analyses included paired frequentist tests and complementary Bayesian paired-sample analyses. Results: Subjective sleep quality improved significantly following the intervention, with a mean reduction in PSQI score of 0.67 points (p < 0.001). In contrast, no meaningful changes were observed in total sleep time (p = 0.28), REM duration (p = 0.26), circadian timing (p = 0.47), or nocturnal minimum heart rate (p = 0.42), as supported by the absence of physiological changes in these parameters. Conclusions: It seems that an individually adjustable sleep system can be able to improve perceived sleep quality in elite athletes without disrupting sleep architecture, circadian regulation, or nocturnal autonomic function. In athletes whose sleep duration and physiological sleep metrics are already near optimal, such micro-environmental interventions may offer a feasible, low-risk means of enhancing recovery by targeting subjective sleep quality. This dimension dissociates from objective sleep measures. Optimizing the sleep surface may therefore represent a practical adjunct to existing recovery strategies in high-performance sport. Full article

Lipid A is a component of lipopolysaccharide (LPS) of Gram-negative bacteria. Previously, we demonstrated that synthesized lipid A derived from Alcaligenes faecalis (ALA) could enhance antigen-specific immunoglobulin (Ig) A and T helper (Th) 17 responses, when ALA was co-administered experimentally with an antigen as a vaccine adjuvant. This raised concerns about the safety of the ALA usage, since IgA and Th17 responses have been suggested to play a pathogenic role in several immune-mediated diseases, including multiple sclerosis (MS). We investigated whether ALA administrations could exacerbate an animal model of MS, Theiler’s murine encephalomyelitis virus (TMEV) infection. TMEV-infected SJL/J mice were administered ALA at various time points, and their neurological signs were observed for 7 weeks. We found that ALA administrations did not exacerbate TMEV-induced inflammatory disease or viral persistence in the central nervous system (CNS), clinically or histologically. Furthermore, ALA administrations did not enhance TMEV-specific humoral and cellular responses, including IgA and Th17 responses. On the other hand, principal component analysis (PCA) of the fecal, not the ileal, samples showed significant changes in the microbiota, characterized by increases in the relative abundance of bacteria belonging to the phylum Bacteroidota, including the genera Alistipes and Bacteroides. Therefore, ALA injections could be safe for use in immune-mediated diseases, whose immunopathology has been associated with IgA and Th17 responses. Full article

This paper presents a PSCAD-based analysis of short-circuit faults and protection characteristics in a real distribution-level microgrid that integrates a 1 MWh battery energy storage system (BESS) with a 500 kW power conversion system (PCS) and a 500 kW photovoltaic (PV) plant connected to a 22.9 kV feeder. While previous studies often rely on simplified inverter models, this paper addresses the critical gap by integrating actual manufacturer-defined control parameters and cable impedances. This allows for a precise analysis of sub-millisecond transient behaviors, which is essential for developing robust protection schemes in inverter-dominated microgrids. The PSCAD model is first verified under grid-connected steady-state operation by examining PV output, BESS power, and grid voltage at the point of common coupling. Based on the validated model, DC pole-to-pole faults at the PV and ESS DC links and a three-phase short-circuit fault at the low-voltage bus are simulated to characterize the fault current behavior of the grid, BESS and PV converters. The DC fault studies confirm that current peaks are dominated by DC-link capacitor discharge and are strongly limited by converter controls, while the AC three-phase fault is mainly supplied by the upstream grid. As an initial application of the model, an instantaneous current change rate (ICCR) algorithm is implemented as a dedicated DC-side protection function. For a pole-to-pole fault, the ICCR index exceeds the 100 A/ms threshold and issues a trip command within 0.342 ms, demonstrating the feasibility of sub-millisecond DC fault detection in converter-dominated systems. Beyond this example, the validated PSCAD model and associated data set provide a practical platform for future research on advanced DC/AC protection techniques and protection coordination schemes in real BESS–PV microgrids. Full article

Carbon sequestration and oxygen release (CSOR) are core regulating functions of terrestrial ecosystems. However, regional assessments often fail to (i) separate scale-driven high supply from per-area efficiency, (ii) detect structural instability and degradation risk from long-term trajectories, and (iii) provide evidence that is comparable across units for management prioritization. Using Minnesota, USA, we integrated satellite-derived net primary productivity (NPP; 1998–2021) with a Quantity–Intensity–Structure (Q–I–S) framework to quantify CSOR, detect trends and change points (Mann–Kendall and Pettitt tests), map spatial clustering and degradation risk (Exploratory Spatial Data Analysis, ESDA), and attribute natural and human drivers (principal component regression and GeoDetector). CSOR increased overall from 1998 to 2021, with a marked shift around 2013 from a slight, variable decline to sustained recovery. Spatially, CSOR showed a persistent north–south gradient, with higher and improving services in northern Minnesota and lower, more degraded services in the south; persistent degradation was concentrated in a central high-risk belt. The Q–I–S framework also revealed inconsistencies between total supply and condition, identifying high-supply yet degrading areas and low-supply areas with recovery potential that are not evident from the totals alone. Climate variables primarily controlled CSOR quantity and structure, whereas human factors more strongly influenced intensity; the interactions of the two further shaped observed patterns. These results provide an interpretable and transferable basis for diagnosing degradation and prioritizing restoration under long-term environmental change. Full article

The development of high-performance wood-based materials has attracted increasing interest as a means of enhancing the mechanical properties of wood for structural applications. Mechanical densification combined with chemical pretreatment is an effective approach; however, many reported methods rely on complex multi-component chemical systems or severe chemical conditions designed to dissolve lignin or hemicelluloses. In this study, a simplified NaOH-only pretreatment followed by hot-press densification was investigated, targeting selective cell-wall plasticization rather than extensive polymer dissolution. Juniper (Juniperus communis), hawthorn (Crataegus monogyna), and birch (Betula pendula) were used as samples of softwood and hardwood species. Wood specimens were pretreated in 1 M NaOH at 145 °C for 10–30 min and subsequently densified by radial compression. Changes in chemical composition were evaluated by HPLC after acid hydrolysis and FTIR spectroscopy, while microstructural changes were examined using SEM. Physical and mechanical properties were assessed through density measurements and three-point bending tests. The results show that NaOH-only pretreatment induces hemicellulose deacetylation and modification of interpolymer linkages without substantial changes in the main wood polymer contents. Densification resulted in effective lumen collapse and a compact microstructure, leading to a significant increase in density and mechanical properties. Overall, the results demonstrate that efficient wood densification and mechanical enhancement can be achieved by promoting polymer mobility through selective cleavage of interpolymer bonds, using a simplified, single-alkali pretreatment that reduces chemical complexity and material loss while avoiding extensive lignin or hemicellulose dissolution. Full article

This study evaluated the damage behavior of 321 austenitic stainless steel under tensile loading by measuring its magnetic properties. The results indicate that, at room temperature, the magnetic properties of 321 stainless steel respond distinctly to mechanical loading. Changes under external stress are primarily attributed to the phase transformation from austenite to martensite. Both coercive force and magnetic Barkhausen noise effectively characterize this material’s deformation and phase transformation processes: the coercive force dynamics curve exhibits an initial rise, followed by a decline with a decrease during the specimen’s necking stage. Magnetic Barkhausen noise is highly sensitive to stress changes, especially during the elastic stage. In situ measurements show that, at a stress of 300 MPa, the magnetic Barkhausen noise peak voltage signal reaches 0.060 V, which is a 100.0% increase compared to the original specimen (0.030 V). Therefore, when assessing the stress state and damage of stainless steel using coercive force and magnetic Barkhausen noise techniques, attention should be paid to the inflection characteristics of the coercive force dynamic curve and the inflection points in the peak values of the magnetic Barkhausen noise voltage signal. These features can be used to effectively monitor crack initiation and propagation in austenitic stainless steel. Full article

This study determined the elastic properties of “green” concrete with cement partially replaced by oil shale ash (OSA) and reinforced with short basalt integral fibers (BIFs). Commercially available Deutsche Basalt Faser (DBF) GmbH Turbobuild Integral basalt fibers were used. There is currently a high demand both for strengthening concrete and applying ecological approaches with respect to circular economy. Oil shale ash is the byproduct of oil shale combustion. Basalt fiber is produced by melting basalt rock. Both BIF and OSA are used as additives in concrete. Cement replacement by OSA non-linearly changes the concrete’s strength properties, and the addition of BIF improves them. An experimental investigation was conducted using four-point bending tests and cube sample compression tests. Theoretical methods such as Voigt and Reuss boundaries, the Halpin–Tsai method, and the Mori–Tanaka method were used to predict the elastic properties of the fabricated samples. The theoretical models can provide useful information, although they may not fully capture the real properties observed experimentally. The results show that BIFs protect against instant brittle destruction. The experiments demonstrated an optimal OSA concentration for a fixed amount of BIF, resulting in the highest load-bearing capacity of the concrete. The addition of either 15% OSA only or 20% OSA and CBF can increase the stiffness of the concrete. This article provides guidance to the construction sector on using OSA and CBF together. Full article

Cancer and Alzheimer’s disease (AD) display an inverse relationship, and there is a need to further explore this interplay. One key genetic contributor to AD is SORL1, the loss of which is thought to be causally related to AD development. SORL1 also appears to be implicated in cancer. To examine SORL1 and its network, this article simulated SORL1 and its interactions via signal-flow Boolean modelling, including in silico knockouts (mirroring in vivo loss-of-function mutations). This model (SKM034) predicted a total of 29 key changes in molecular relationships following the loss of SORL1 or another highly connected protein (ERBB2). Literature validation demonstrated that 2 of these predictions were at least partially validated experimentally, whilst 27 were Potentially Novel Predictions (PNPs). Complementing the in-depth relationship analyses was signal flow analysis through the network’s structure, validated using cell line and cancer patient RNA-seq data. Correct prediction rates for these analyses reached 60% (statistically significant relative to a random model). This article demonstrates the clinical relevance of this Alzheimer’s-related network in a cancer context and, through the PNPs, provides a strong starting point for in vitro experimental validation. As with previously published models using similar methods, the model may be reanalysed in different contexts for further discoveries. Full article

Instead of being a mechanism used by management in the name of productivity, it is suggested that social power theory can be combined with the extended marketing mix to empower groups of actors in organisations. These two foundational rubrics usually perpetuate the status quo, but when used with a fresh approach, they may be used to improve engagement. The question is how these two theories can be used to describe performance, connections and power relationships, and how might this change organisations for the better? This conceptual paper combines these two rubrics in a single heuristic that reflects hidden currents in organisations. Understanding how these intersections work can foster greater empowerment for actors and produce efficiencies for management. Learning how to use the points of leverage would be a significant step forward for marketing within and between organisations. Full article

Background: The albumin–bilirubin (ALBI) grade provides an objective assessment of hepatic reserve, but the need for calculation by means of a formula has hampered its use at the bedside. This study aimed to develop simple cut-off values for ALBI grade and validate its performance in a large multi-center real-world cohort. Methods: A mathematical simulation evaluated every possible ALBI pair that falls within the Child–Pugh classification (CP) A range, discretized to 0.1 increments. Cut points for patient stratification without equation-based calculation were derived. Validation was conducted with the Chang Gung Research Database (CGRD), which contains data from 10 hospitals in Taiwan. Patients with same-day albumin and bilirubin measurements in 2024 were included. Results: Mathematical modeling identified clinically applicable cutoffs—albumin ≥ 4.4 g/dL or ≤3.5 g/dL and bilirubin ≥ 2.4 mg/dL—with further refinement at albumin 4.0 g/dL and bilirubin ≥ 1.0 mg/dL. Among 7583 CP-A patients, 82% were directly classifiable without computation, with consistent applicability across chronic liver disease and hepatocellular carcinoma (HCC) subgroups. Equation dependence increased only slightly in the HCC group, confirming robustness across disease severities. Conclusions: Simplified cutoff rules derived from mathematical modeling and validated in a multi-center cohort enable rapid recognition of ALBI grade in most CP-A patients. This approach enhances the clinical usability of ALBI and supports its integration into patient care, clinical trials, and treatment allocation. Full article

RNA-directed DNA methylation (RdDM), a new plant breeding technology, induces epigenetic modifications that can be inherited even after segregation of the responsible transgene. The transgene-free descendants (null segregants) are potentially exempt from the regulation of genetically modified plants. To evaluate the risks of potential unintended molecular changes in the null segregants of RdDM-positive plants, we produced null segregants (S44end2-null) from a transgenic tobacco line in which RdDM targeting the promoter of the transgene was introduced. Comprehensive multi-omics analyses, including transcriptomics, proteomics, and metabolomics, were conducted using S44end2-null and wild-type (WT) plants. Principal component analysis demonstrated clear separation of the transcriptomic and proteomic profiles of the two groups. The metabolomic profiles of S44end2-null plants exhibited considerable overlap with those of WT plants. Proteomic analysis of the null segregants of tobacco plants transformed with an empty vector demonstrated distinct cluster separation from WT plants. Because only sporadic DNA methylation on the tobacco genome was expected by the RdDM construct used in this study, the observed differences in omics profiles are considered to be significantly influenced by genetic variation accumulated during the transformation and regeneration processes (somaclonal variation). The safety assessment points for null segregants using RdDM technology are discussed. Full article

Background: No Fourier transform infrared (FTIR) spectroscopy studies have directly evaluated adrenalectomy vessels, the technique’s established ability to probe collagen/elastin-associated spectral features and lipid peroxidation-related signatures, and protein structural damage. Stable gastric pentadecapeptide BPC 157 therapy was found to maintain the vascular function under severe stress, as FTIR spectroscopy recently demonstrated rapid peptide-induced molecular changes in healthy rat blood vessels, particularly in lipid content and protein secondary structure. Methods: To extend these findings and highlight the BPC 157 vascular background in the special circumstances of the course following unilateral adrenalectomy, abdominal aortas were collected at 15 min, 5 h, and 24 h after unilateral adrenalectomy for the FTIR spectroscopy assessment. Results: FTIR spectra were acquired, preprocessed, and analyzed using principal component analysis (PCA), support vector machine discriminant analysis (SVMDA), and band-specific statistics. BPC 157 (10 ng/kg intragatrically immediately after unilateral adrenalectomy) produced a clear, reproducible separation of aortic spectra from control samples at all time points. The main discriminatory spectral signatures were observed in three regions, including amide I and amide II (protein-related bands, consistent with collagen/elastin contributions) and lipid C–H stretching bands. These spectral signatures are consistent with early extracellular matrix reinforcement and membrane preservation in the vascular wall and align with the recovering effect on the lesions in counteraction of the severe vascular and multiorgan failure, attenuation/elimination of thrombosis and blood pressure disturbances in various occlusion/occlusion-like syndromes. Conclusions: Together, after unilateral adrenalectomy, the FTIR data provide molecular-level spectral signatures consistent with rapid remodeling of the aortic wall toward a more structurally stable and functionally favorable state. Full article