Search Results (1,757)

The marine carbonate reef–shoal reservoirs in the gentle slope platform margin of the M block, eastern Sichuan Basin, were well developed during the Changxing Period in late Permian and represent a favorable carbonate reservoir play for petroleum exploration. The lack of effective research methods has hindered the analysis of their unique sedimentary characteristics and controlling factors. Based on cores, thin sections, well logs, testing analyses, and high-resolution 3D seismic data, this study analyzes the lithological associations, microfacies types, reservoir physical properties, and seismic reflection characteristics of reef–shoal reservoirs. On this basis, the reef–shoal sedimentary characteristics and controlling factors were analyzed. The main conclusions are as follows: (1) Two major categories and eight subcategories of petrography were identified in marine carbonate reef–shoals, and five microfacies were identified: reef base, reef core, reef flank, reef-top–shoal, and inter-reef sea. Among these, the reef-top–shoal constitutes the optimal reservoir, while the reef flank develops secondary reservoirs. (2) The reef–shoals exhibit an external mound or wedge-shaped reflection, with internally discontinuous or chaotic reflections. Discontinuous reflections are observed at the top, while onlap terminations are present on its flanks. (3) The vertical accretion of the marine reef–shoals is small, but the platform margin belt is wide in planar, multiple rows reef–shoal bodies are identified, reflecting their small scale, discrete planar distribution, rapid lateral migration, and diverse stacking patterns. (4) The regional gentle slope marine platform margin geological setting, tectonic paleogeomorphology, and high-frequency sea level fluctuation collectively control the sedimentary structure and the formation of high-quality reservoirs of the marine reef–shoal complex. This research provides guidance for petroleum exploration and favorable reservoir prediction in the marine carbonate reservoirs of the Sichuan Basin. Full article

Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data on treatment feasibility, efficacy, and related toxicities, with a specific focus on immune-related adverse events (irAEs). Methods: We conducted a retrospective analysis of patients who completed at least the neoadjuvant sequence of pembrolizumab combined with chemotherapy for early-stage TNBC at Montpellier Cancer Institute from April 2022 to July 2024. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The pathological complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes (ypT0/Tis ypN0). Results: We reviewed data from 92 patient records. The median age at diagnosis was 50 years (range: 27–76). The history of autoimmune disease was noted in 3.2% of patients. Grade 3–4 irAEs were observed in 20% of patients and included hepatitis (8.6%), colitis (3.3%), skin toxicity (2.1%), myocarditis (2%), arthralgia (1%), autoimmune hemolytic anemia (1%), hypothyroidism (1%), and adrenal insufficiency (1%). No treatment-related deaths were reported. Immunotherapy was discontinued due to irAEs in 29.3% of patients in the study population. The pCR rate was 61,1%, with no significant association between the number of neoadjuvant pembrolizumab cycles and the pCR rate (p = 0.7). Patients experiencing grade 3–4 irAEs had a pCR rate of 80%, compared to 56.7% in those without such toxicities (p = 0.079). Initial positivity of antinuclear antibodies (ANA) was not associated with an increased incidence of irAEs. Conclusions: The immune-related adverse events and efficacy data observed in our cohort were broadly comparable to those reported in the KEYNOTE-522 trial, with no treatment-related deaths. Patients with grade 3–4 irAEs tended to have higher pCR rates. Full article

Automated recognition of rock mass discontinuities in vegetated high-slope terrains remains a challenging task critical to geohazard assessment and slope stability analysis. This study presents an integrated framework combining close-range UAV photogrammetry with an Improved Superpoint Transformer (ISPT) for semantic segmentation and structural characterization. High-resolution UAV imagery was processed using an SfM–MVS photogrammetric workflow to generate dense point clouds, followed by a three-stage filtering workflow comprising cloth simulation filtering, volumetric density analysis, and VDVI-based vegetation discrimination. Feature augmentation using volumetric density and the Visible-Band Difference Vegetation Index (VDVI), together with connected-component segmentation, enhanced robustness under vegetation occlusion. Validation on four vegetated slopes in Buyun Mountain, China, achieved an overall classification accuracy of 89.5%, exceeding CANUPO (78.2%) and the baseline SPT (85.8%), with a 25-fold improvement in computational efficiency. In total, 4918 structural planes were extracted, and their orientations, dip angles, and trace lengths were automatically derived. The proposed ISPT-based framework provides an efficient and reliable approach for high-precision geotechnical characterization in complex, vegetation-covered rock mass environments. Full article

Background and Objectives: Behçet’s disease (BD) is a multisystem inflammatory disorder with significant physical, psychological, and social burdens. However, patient-reported outcomes and subjective symptom experiences remain under-recognized in clinical practice. This study aimed to provide a patient-centric analysis of the disease burden, treatment challenges, and unmet needs in BD. Materials and Methods: A multinational cross-sectional study was conducted using a structured questionnaire among 528 BD patients recruited from online support groups and a specialized clinic. The questionnaire gathered information about participants’ backgrounds, medical histories, how symptoms affected them, psychological and social factors, side effects of treatments, and their suggestions for better care. Data were analyzed descriptively. Results: The mean age of the participants was 41.4 years, and 69.3% were male. The most common symptoms that significantly affected daily life were severe fatigue (82.8%), joint pain and swelling (79.0%), and neurological issues (74.1%). Nearly half of patients perceived that fatigue (49.1%) and neurological symptoms (45.1%) were underestimated by healthcare providers. Psychological distress was prevalent, with 74.1% of participants reporting either depression or anxiety. Side effects related to treatment were frequently encountered (56.3%), resulting in treatment discontinuation for 53.4% of the individuals. The main unmet needs identified were fatigue reduction (59.1%), pain management (43.0%), and the minimization of side effects (59.1%). Furthermore, patients expressed a desire for enhanced communication (62.9%), validation of their unobserved symptoms (74.1%), and comprehensive disease education (67.6%). Conclusions: BD imposes a profound multidimensional burden, with a significant disconnect between patient experiences and their perception of clinical recognition. Fatigue, pain, psychological distress, and treatment-related challenges contribute substantially to unmet needs. A patient-centered approach emphasizing communication, symptom validation, and holistic support is essential to improving care and quality of life in BD. Full article

A major danger that significantly raises the possibility of deep coal mining accidents is the delayed water influx from the bottom plate, which is brought on by the activation of tiny faults brought on by mining at the working face of the restricted aquifer. This study develops 17 numerical models utilizing FLAC3D simulation software 6.00.69 to clarify the activation and water inburst mechanisms of minor faults influenced by various parameters, incorporating fluid–solid coupling effects in coal seam mining. The developmental patterns of the stress field, displacement field, plastic zone, and seepage field of the floor rock layer were systematically examined in relation to four primary factors: aquifer water pressure, minor fault angle, fracture zone width, and the distance from the coal seam to the aquifer. The results of the study show that the upper and lower plates of the minor fault experience discontinuous deformation as a result of mining operations. The continuity of the rock layers below is broken by the higher plate’s deformation, which is significantly larger than that of the lower plate. The activation and water flow into small faults are influenced by many elements in diverse ways. Increasing the distance between the coal seam and the aquifer will make the water conduction pathway more resilient. This will reduce the amount of water that flows in. On the other hand, higher aquifer water pressure, a larger fracture zone, and a fault that is tilted will all help smaller faults become active and create channels for water to flow into. The gray relational analysis method was used to find out how sensitive something is. The sensitivities of each factor to water influence were ranked from high to low as follows: distance between the aquifer and coal seam (correlation coefficient 0.766), aquifer water pressure (0.756), width of the fracture zone (0.710), and angle of the minor fault (0.673). This study statistically elucidates the inherent mechanism of delayed water instillation in minor faults influenced by many circumstances, offering a theoretical foundation for the accurate prediction and targeted mitigation of mine water hazards. Full article

The increase in population and demand for the various needs of citizens increases the interaction with the geo-environment. Thus, the rate of natural events affecting daily human life increases. Such an event occurred on a rock cliff in a densely populated area in İstanbul (Türkiye). More than four rock blocks (approximately 3–5 m³) belonging to the Paleozoic sequence of İstanbul, composed of nodular limestone with sandy-clay interlayers, detached and fell. The blocks traveled along a path of approximately 60 m and stopped by crushing a couple of buildings downslope. The path was rough and contained various surface conditions (e.g., bedrock, talus, and plants). This study was initiated by the examination of the dimensions of failed rock blocks, their paths, and topographic conditions. Unmanned vehicles (drones) facilitated the generation of 3D numerical models of topographic changes on the site. Quantifying discontinuity properties (such as persistence, spacing, roughness, etc.) and defining weathering properties comprises the second stage, along with sampling. Based on digital topographic data and field observations, cross-sections were defined by means of possible rockfall areas within the area of potentially unstable blocks. Numerical analysis and rockfall analysis were conducted along these critical sections. Interpretation of laboratory data and results obtained from numerical studies leads to an understanding of the mechanism of the recent rockfall event and demonstrates the most critical areas to be considered and reinforced. The research comprises proposing appropriate reinforcement techniques due to the strong Turkish regulations along the “Bosphorus Waterfront Protected Zone”. The study advises pre-cleaning of potentially unstable blocks after a fence production on paths where rocks could fall, and rock anchors in some localities with varying lengths. The latest part of the research covers the re-assessment of mitigation processes with numerical models, which shows that the factor of safety increased to the desired levels. The reinforcement applications at the site match well with the proposed prevention methods. Full article

A statistical analysis of wind power development in each U.S. state from 2000–2022 shows that the Production Tax Credit strongly promoted wind power development, especially when it was due to expire, and producers rushed to qualify. This implies that the Inflation Reduction Act should also have an important effect in promoting wind power, with an exaggerated effect when developers perceive that tax credits will be discontinued. Physical wind power potential is positively related to wind power development among states. States with high potential selectively pass Renewable Portfolio Standards, but they have no statistically significant influence on capacity developed among the subset of states participating in wind power development. No other policy variables considered—natural gas prices, state permitting systems, electrical restructuring, enrollment in regional transmission organizations—displayed any practically useful association with wind power development nationally over time or among states. Full article

In this study, we evaluated the returns and return volatility of a Brazilian stablecoin linked to fertilizers during periods preceding its discontinuation. In light of the safe haven literature, we also tested the correlation between this stablecoin and a traditional cryptocurrency, Bitcoin, and modeled its behavior during periods of Bitcoin’s extreme returns. In terms of methodology, we employ GARCH-family models (including DCC-GARCH) to analyze daily data from 1 December 2022 to 16 January 2025. We also employ an analysis using Large Language Models (LLMs), evaluating the stablecoin time series considering the period of its discontinuation. The results indicated that as the discontinuation date approached, the stablecoin exhibited statistically significant lower returns and higher volatility. While the DCC-GARCH indicated no correlation between the assets, we found that the stablecoin’s returns exhibited a negative relationship with Bitcoin’s extreme returns, challenging its potential efficacy as a safe haven. This article offers practical contributions for digital asset investors, indicating that even physically backed stablecoins, designed for stability, are subject to significant volatility, idiosyncratic risks, and potential discontinuation. Full article

Geometric discontinuities are unavoidable in additively manufactured polymer components and can significantly alter their mechanical response; however, their effects are rarely quantified in a systematic and geometry-comparative manner. In this study, the tensile behavior of FDM-printed PLA+ specimens with three different geometries—dog-bone, circular-hole, and U-notched (manufactured and tested in accordance with ASTM D638 (Type IV))—was experimentally and numerically investigated. Tensile tests were conducted using a universal testing machine equipped with an extensometer, while finite element simulations were performed using an experimentally calibrated Ramberg–Osgood-based elastic–plastic material model. The dog-bone specimens exhibited an ultimate tensile strength (UTS) of 41–43 MPa and a Young’s modulus of 3.06 GPa, representing the intrinsic material response under nearly homogeneous stress conditions. Circular-hole specimens maintained comparable strength (38–42 MPa) but showed reduced ductility (1.4–1.6%) and a slightly increased apparent modulus of 3.17 GPa due to localized deformation. In contrast, U-notched specimens displayed the highest apparent modulus (≈5.30 GPa) and nominal UTS (46–49 MPa), accompanied by a pronounced reduction in ductility (0.9–1.0%), indicating severe stress concentration and predominantly brittle fracture behavior. Finite element analysis showed excellent agreement with experimental results, with peak von Mises stresses reaching approximately 42 MPa for all geometries, corresponding closely to the experimentally measured tensile strength. These results demonstrate that geometric discontinuities strongly govern stress localization, apparent stiffness, and fracture initiation in FDM-printed PLA+ components. The validated Ramberg–Osgood-based modeling framework provides a reliable tool for predicting geometry-dependent mechanical behavior under quasi-static loading and supports geometry-aware design of additively manufactured polymer structures. Full article

Accurate prediction of the shear strength of rock discontinuities requires accounting for surface roughness, which is a factor neglected in the classical Mohr–Coulomb criterion. This study proposes a fractal-enhanced Mohr–Coulomb model that incorporates the surface fractal dimension Ds as a geometric state variable governing both the cohesion and internal friction angle. The fractal dimension is treated as an objective, scale-invariant descriptor, computable via established methods, such as box-counting and power spectral density analysis, which are known to yield consistent results when applied to joint topography. The model predicts a nonlinear increase in shear strength with Ds, producing a dynamically adjustable failure envelope that can exceed the classical Mohr–Coulomb estimates by 25–40% for rough joints, which is consistent with trends observed in experimental shear tests. By linking strength parameters directly to measurable surface geometry, the framework provides a physically interpretable bridge between micro-scale roughness and macro-scale mechanical response. Although the current formulation assumes monotonic, dry, and quasi-static conditions, the explicit dependence on Ds offers a foundation for future extensions that incorporate anisotropy, damage evolution, and hydro-mechanical coupling. Full article

Background/Objectives. Chronic benzodiazepine (BDZ) use is frequently maintained beyond recommended durations due to neuroadaptation, psychological dependence, and withdrawal-related issues. Passiflora incarnata L., herba (P. incarnata) has shown anxiolytic and GABAergic activity that may mitigate withdrawal symptoms, while cognitive-behavioural therapy (CBT) targets maladaptive beliefs and behaviours sustaining BDZ misuse. This study investigates the independent and interactive effects of P. incarnata and CBT on BDZ dose reduction during a three-month tapering program. Methods. This retrospective observational study included 186 outpatients with anxiety or depressive disorders in clinical remission undergoing BDZ tapering, of whom 93 received a dry extract of P. incarnata as adjunctive treatment and 93, matched for diagnosis, age and sex, followed a standard tapering protocol. BDZ doses were assessed at baseline and three months. CBT was recorded as a binary variable based on the information documented in the medical records. An ANCOVA was performed to assess the impact of CBT and P. incarnata on BDZ reduction (change in mg diazepam equivalents), adjusting for sex, age, education, baseline anxiety and depression scores, initial BDZ and antidepressant dosage. A subgroup analysis was conducted to investigate the role of P. incarnata dosage in BDZ reduction. Results. Both CBT and P. incarnata were associated with significantly greater reductions in BDZ dosage at three months (CBT: p = 0.005, effect size: 0.032; P. incarnata: p < 0.001, effect size: 0.128). A significant interaction between CBT and P. incarnata was also observed (p = 0.037, effect size: 0.018), indicating a synergistic effect when both interventions were combined. Baseline sociodemographic characteristics, BDZ and antidepressant dosage and symptom severity did not differ significantly between groups. Patients taking 400–600 mg of P. incarnata dry extract showed a higher BDZ reduction compared to those taking 200 mg. Conclusions. These findings suggest that P. incarnata and CBT exert independent yet complementary effects in supporting BDZ tapering. Their combination appears to enhance dose reduction beyond either intervention alone, supporting a multimodal approach that addresses both neurobiological and psychological components of BDZ addiction. Prospective controlled studies are needed to confirm these results and to clarify their impact on long-term discontinuation outcomes. Full article

The historic Rockborn strain of the canine distemper virus was widely used as a vaccine, but its use was discontinued due to safety concerns. Yet, Rockborn-like canine distemper virus strains are still used in some vaccine formulations. Genetic analysis of this strain was previously limited to the H gene, leaving its full evolutionary and pathogenic potential unclear. This study aimed to determine the complete genome sequence of the Rockborn strain to reconstruct its origin, understand its evolution, and provide a reference for improving diagnostics and future research on virulence markers. An amplicon-based sequencing protocol using MinION nanopore technology was employed to determine the complete genome of the Rockborn-46th laboratory strain. The genome was assembled, annotated, and analyzed in comparison with 223 genomes. The complete genome of the Rockborn strain was 15,690 nucleotides in length. Phylogenetic analysis revealed that Rockborn forms a unique lineage with field isolates from a masked civet in China and a dog in the United States. Crucially, a significant recombination event was identified, showing that the Rockborn strain acted as a parental strain, contributing its F and H genes to create mosaic viruses. The full-genome characterization of the Rockborn strain confirms that Rockborn-like viruses persist and actively contribute to the evolution of canine distemper virus through recombination. This finding highlights the inadequacy of single-gene analysis for diagnostics and surveillance, and underscores the necessity of whole-genome sequencing to accurately track the virus epidemiology and evolution. Full article

This paper presents an easy-to-use analytical method for stability analysis of composite plates with dense bidirectional microstructure. The main characteristic feature of such a defined composite is that due to its periodic nature the obtainable governing partial differential equations are characterised by discontinuous, strongly oscillating coefficients. Such cases bring many difficulties during derivation of their solution. In order to simplify calculations, the initial governing equations are transformed with the use of the tolerance averaging technique, so a system of partial differential equations with constant coefficients is obtained. The most important finding of the presented work is that the form of the mentioned equations is similar to the classic equations, which describe the stability issue of the thin homogeneous plate. Consequently, the analytical solution to such issues is easily obtainable. Moreover, when compared to, for example, finite element method (FEM) analysis, it requires substantially less computation resources, which can be perceived as its superior feature. Therefore, the proposed method is convenient for engineering applications. In this paper, a comparative analysis of the results obtained from the proposed analytical models with the results obtained from the FEM has been carried out. The impact of materials and dimensions of microstructure on the values of critical normal and shear forces has also been analysed. Full article

Background: β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors demonstrated amyloid-lowering efficacy but failed in phase II/III clinical trials due to adverse effects and limited disease-modifying outcomes. This study employed an integrated network pharmacology and molecular docking approach to quantitatively elucidate the multitarget mechanisms of 4 (phase II/III) discontinued BACE1 inhibitors (Verubecestat, Lanabecestat, Elenbecestat, and Umibecestat) and the preclinical compound AM-6494 in Alzheimer’s disease (AD). Methods: Drug-associated targets were intersected with AD-related genes to construct a protein–protein interaction (PPI) network, followed by topological analysis to identify hub proteins. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using statistically significant thresholds (p < 0.05, FDR-adjusted). Molecular docking was conducted using AutoDock Vina to quantify binding affinities and interaction modes between the selected compounds and the identified hub proteins. Results: Network analysis identified 10 hub proteins (CASP3, STAT3, BCL2, AKT1, MTOR, BCL2L1, HSP90AA1, HSP90AB1, TNF, and MDM2). GO enrichment highlighted key biological processes, including the negative regulation of autophagy, regulation of apoptotic signalling, protein folding, and inflammatory responses. KEGG pathway analysis revealed significant enrichment in the PI3K–AKT–MTOR signalling, apoptosis, and TNF signalling pathways. Molecular docking demonstrated strong multitarget binding, with binding affinities ranging from approximately −6.6 to −11.4 kcal/mol across the hub proteins. Umibecestat exhibited the strongest binding toward AKT1 (−11.4 kcal/mol), HSP90AB1 (−9.5 kcal/mol), STAT3 (−8.9 kcal/mol), HSP90AA1 (−8.5 kcal/mol), and MTOR (−8.3 kcal/mol), while Lanabecestat showed high affinity for AKT1 (−10.6 kcal/mol), HSP90AA1 (−9.9 kcal/mol), BCL2L1 (−9.2 kcal/mol), and CASP3 (−8.5 kcal/mol), respectively. These interactions were stabilized by conserved hydrogen bonding, hydrophobic contacts, and π–alkyl interactions within key regulatory domains of the target proteins, supporting their multitarget engagement beyond BACE1 inhibition. Conclusions: This study demonstrates that clinically failed BACE1 inhibitors engage multiple non-structural regulatory proteins that are central to AD pathogenesis, particularly those governing autophagy, apoptosis, proteostasis, and neuroinflammation. The identified ligand–hub protein complexes provide a mechanistic rationale for repurposing and optimization strategies targeting network-level dysregulation in Alzheimer’s disease, warranting further in silico refinement and experimental validation. Full article

Background: Non-absorbable polyvinyl alcohol sponges (Merocel) are widely used in otolaryngology for nasal and ear packing but are prone to bacterial colonization and biofilm formation, which may increase infection risk and drive frequent use of systemic antibiotics. Sustained-release drug delivery systems enable prolonged local antiseptic activity at the site of packing while minimizing systemic exposure. Methods: We developed a sustained-release varnish containing chlorhexidine (SRV-CHX) and coated sterile Merocel sponges. Antibacterial, in vitro, activity against Staphylococcus aureus and Pseudomonas aeruginosa was evaluated using kinetic diffusion assays on agar, optical density (OD₆₀₀) measurements of planktonic cultures, drop plate, ATP-based viability assays, biofilm analysis by MTT metabolic assay, crystal violet bio-mass staining, high-resolution scanning electron microscopy (HR-SEM), and spinning disk confocal microscopy. Results: SRV-CHX-coated sponges produced sustained zones of inhibition on agar plates for up to 37 days against S. aureus and 39 days against P. aeruginosa, far exceeding the usual 3–5 days of clinical sponge use. Planktonic growth was significantly reduced compared with SRV-placebo, and a bactericidal effect persisted for up to 16 days for S. aureus and 5 days for P. aeruginosa before becoming predominantly bacteriostatic. Biofilm formation was markedly inhibited, with suppression of metabolic activity and biomass for at least 33 days for S. aureus and up to 16 days for P. aeruginosa. HR-SEM and confocal imaging confirmed sparse, discontinuous biofilms and predominance of non-viable bacteria on SRV-CHX-coated sponges compared with dense, viable biofilms on the placebo controls. Conclusions: Coating Merocel sponges with SRV-CHX provides prolonged antibacterial and anti-biofilm activity against clinically relevant pathogens. This strategy may reduce dependence on systemic antibiotics and improve infection control in nasal and ear packing applications in otolaryngology. Full article