Search Results (26,052)

HER2-low breast cancer, also known as IHC 1+ or IHC 2+ without ERBB2 amplification, is a new concept in the biology of breast cancer that has removed the binary classification of HER2-positive or HER2-negative breast cancer. The recent introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd), has improved therapeutic outcomes for HER2-low breast cancer by demonstrating high efficacy in HER2-low tumors through efficient payload delivery. However, differences in ADC efficacy exist among HER2-low breast cancer patients, with tumor cells showing resistance to ADCs. Recent research indicates that the tumor microenvironment (TME) plays a critical role in determining the efficacy of ADCs against tumor cells. TME creates a barrier to the delivery of ADCs to tumor cells that show resistance to ADCs. This review article aims to highlight the current understanding of the biology of HER2-low breast cancer and its response to ADCs with reference to the tumor microenvironment. Full article

This study reports the synthesis, spectroscopic characterization, and biological evaluation of a novel moxifloxacin hydrazide derivative (MOX-H) and its metal complexes with Co(II), Ni(II), Cu(II), VO(IV), and Gd(III). The ligand was synthesized by hydrazinolysis of moxifloxacin hydrochloride, and the resulting hydrazide was subsequently complexed with the respective metal salts. The interaction between MOX-H and the metal ions yielded the corresponding complexes, formulated as [Co(H₂O)Cl(MOX-H)₂]Cl·2.5H₂O, [Ni(H₂O)Cl(MOX-H)₂]Cl.4.5H₂O, [VO(MOX-H)₂]SO₄.3.5H₂O, [Gd (H₂O)(MOX-H)₂(NO₃)₂]NO₃.2H₂O, and [Cu(MOX-H)₂(H₂O)Cl]Cl·xH₂O (where x = 2, 2.5, 0.5, for products synthesized via template, microwave-assisted, and hydrothermal methods, respectively). The synthesized analogues were characterized by elemental analysis (CHN), FT-IR, UV-visible, and ¹H NMR spectroscopy, and mass spectrometry, as well as thermogravimetric (TG/DTG) and magnetic measurements. FT-IR spectra confirmed coordination through the hydrazide carbonyl and amine groups, while UV–visible and magnetic data indicated predominantly octahedral geometries. The thermal behavior exhibited multistep decomposition with activation parameters supporting exothermic processes. When compared to the free ligand, the metal complexes showed increased antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungus species, particularly for the Co(II) and Cu(II) complexes, which showed the largest inhibition zones. The Cu(II)–MOX-H complex exhibited the lowest MIC values (4.88–9.76 µg/mL) among all tested compounds, confirming its outstanding antibacterial potency and high sensitivity compared to the free ligand and standard drug. Cytotoxicity assays demonstrated selective anticancer activity, with the Cu(II)–MOX-H complex showing the highest potency (IC₅₀ ≈ 2.95 µM against MCF-7 and IC₅₀ ≈ 0.98 µM against HepG-2), while maintaining minimal toxicity toward normal cells. These findings were corroborated by molecular docking investigations, which showed that the MOX-H complexes had substantial binding affinities (−9 to −10 kcal/mol) toward DNA topoisomerase II, consistent with their observed biological effects. Full article

This study examines the role of Paradoxical Leadership (PL) in enhancing sustainable service performance in Egypt’s hotel industry, with Organizational Citizenship Behavior (OCB) serving as a key mediating mechanism. Moving beyond conventional performance frameworks, the research examines how the dual nature of PL behaviors encourages discretionary employee actions that advance social sustainability, employee well-being, responsible service delivery, and long-term organizational resilience. Employing a survey-based quantitative design, data were collected from 397 hotel employees in Egypt using a structured questionnaire assessing overall PL, its five core dimensions, and OCB. A structured questionnaire was used to measure overall PL, its five core dimensions, OCB, and sustainable service performance. The data were analyzed using SPSS Version 24 and WarpPLS 8, confirmatory factor analysis, reliability analysis, and regression-based mediation analysis to examine the relationships among the study variables. The findings reveal that PL positively influences sustainable service performance, while OCB not only enhances service outcomes but also significantly mediates the relationship between PL and performance. In addition, each dimension of PL—balancing self- and other-centeredness (SO), maintaining distance while fostering closeness (CD), treating employees uniformly while recognizing individuality (UI), preserving decision control while encouraging autonomy (CA), and enforcing work requirements while allowing flexibility (RF)—significantly strengthens employees’ citizenship behaviors. Full article

Background/Objectives: Enteropathogenic Escherichia coli O157:H7 infection disrupts intestinal homeostasis, causing dysbiosis, barrier dysfunction, and inflammation. This study aimed to evaluate the protective efficacy and mechanisms of a novel probiotic, Bacteroides thetaiotaomicron type strain ATCC 29148, isolated from goat feces, against E. coli O157:H7-induced colitis. Methods: This study assessed the protective potential of the probiotic strain Bacteroides thetaiotaomicronBT6 and BT7 in vitro for GI tolerance, adhesion, and no adverse effects were observed. For the in vivo experiment, male C57BL/6J mice were divided into groups treated with Bacteroides thetaiotaomicron (BT6), PBS, E. coli O157:H7, or a combination. We employed integrated analyses including 16S rRNA gene sequencing, antioxidant status, cytokine profiling, and short-chain fatty acid (SCFA) measurement. Results: In vitro, Bacteroides thetaiotaomicron (BT6 and BT7) showed high gastrointestinal tolerance (71.89–93.22% survival). In vivo, it significantly mitigated infection-associated weight loss and disease activity (p < 0.05). Probiotic treatment enhanced barrier integrity, reduced colonic inflammation, and modulated systemic immune responses, notably increasing anti-inflammatory IL-10 while decreasing pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 (p < 0.05). It also alleviated oxidative stress by reducing malondialdehyde (MDA) and elevating antioxidant enzymes (SOD, CAT, GSH) and ATP. Fecal SCFA profiling revealed increased propionic and butyric acid. 16S sequencing indicated that B. thetaiotaomicron (BT6) administration increased beneficial families (Lactobacillaceae, Muribaculaceae) and suppressed pathobionts. Conclusions: B. thetaiotaomicron (BT6) probiotic with potential for mitigating enteropathogenic infection, an effect mainly determined by its capacity to reestablish the intestinal epithelial barrier and enhance global host health, and modulating the inflammatory response Full article

Background: Precise staging of prostate cancer is vital for treatment planning and prognosis. While [⁶⁸Ga]Ga-PSMA-11 PET-CT has demonstrated high diagnostic accuracy in detecting metastatic disease, the interpretation of indeterminate or potentially benign PSMA-avid bone lesions remains a clinical challenge in routine practice. Methods: We conducted a retrospective single-centre study involving 214 patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET-CT between January 2021 and January 2024. Patients with prior known bone metastases or alternative PSMA radiotracers were excluded. Only those with follow-up imaging were included for diagnostic accuracy analysis. Follow-up modalities included PSMA PET-CT, CT, MRI, and bone scintigraphy. Final classification (metastatic or benign) was based on radiological and clinical assessment. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using follow-up imaging as the reference standard. Lesions classified as indeterminate were analysed separately and excluded from diagnostic performance calculations. Results: Of the 214 included patients, 142 had follow-up imaging. Among 80 patients with bone lesions initially reported as metastatic, 74 (92.5%) were confirmed. Among 28 patients initially reported as having benign bone lesions, 26 (92.9%) remained benign on follow-up. Thirty-four patients with indeterminate lesions were reviewed; four were ultimately metastatic. Excluding indeterminate cases, sensitivity, specificity, PPV, and NPV were 97.4%, 86.7%, 94.9%, and 92.9%, respectively. Diagnostic discordance was primarily associated with benign uptake in the ribs, iliac bones, pubic rami and degenerative changes. Conclusions: [⁶⁸Ga]Ga-PSMA-11 PET-CT shows excellent sensitivity and positive predictive value for detecting metastatic bone disease in prostate cancer. However, benign lesions may also exhibit uptake, emphasising the importance of integrating imaging results with PSA levels, Gleason scores, and TNM staging. Prospective studies are needed to validate these findings and assess their impact on long-term outcomes. Full article

While recent research has extensively investigated the feasibility of incorporating various agricultural by-products as aggregate replacements in concrete, the specific potential of crushed date kernel (CDK) remains insufficiently characterized despite their abundance. This study evaluates the performance of concrete incorporating CDK as a partial replacement for fine aggregates at volumetric ratios ranging from 5% to 30%. The experimental program was oriented to find the major properties of the mixes, such as compressive strength, splitting tensile strength, flexural strength, and bonding, in addition to the Ultrasonic Pulse Velocity, water absorption, density, and thermal conductivity. The compressive strength of the standard mixture was 26.73 MPa, the flexural strength was 4.47 MPa, and the thermal conductivity was 1.99 W/m·K after 28 days. A compressive strength of 26.78 MPa was recorded for a 5% substitution, but the flexural strength of 4.85 MPa was greater, along with a reduction in the thermal conductivity of 1.86 W/m·K. Higher replacement ratios led to a gradual loss of mechanical strength, whereas 30% replacement gave a corresponding stress of 19.65 MPa. However, thermal conductivity continued to decrease to a value of 1.27 W/m·K, indicating a better insulation capacity. Furthermore, the TOPSIS multi-criteria decision-making analysis demonstrated a robust classification across multiple weighting combinations. The analysis identified the 5% replacement ratio as the optimum for operating and the 10% replacement as optimum on a sustainability basis. Full article

This study presents an experimental investigation into a novel hybrid strengthening system for reinforced concrete (RC) beams that combines externally bonded carbon-fiber-reinforced polymer (CFRP) sheets with a spray-applied polyurea coating (Linex XS-350). Seven beams were tested under four-point bending to evaluate the effects of two main parameters, CFRP thickness and single vs. double layers, and polymer coating configurations, i.e., none, thin with 2 mm, thick with 4 mm, and embedded. The coating was intended to act as an elastic confinement layer that mitigates peeling stresses and enhances CFRP concrete bond performance. The results demonstrated significant improvements in strength, ductility, and strain capacity for coated specimens compared with CFRP-only beams. The inclusion of Linex increased the ultimate load by up to 24% in single-layer beams and 20% in double-layer beams, while bottom-fiber strain at failure increased by more than fivefold, indicating enhanced CFRP utilization. The uncoated beams failed prematurely by CFRP peeling, whereas the coated and embedded specimens transitioned to CFRP rupture with more gradual and ductile behavior. The combined use of multiple CFRP layers and polymer coating produced the most effective performance, with the double-layer embedded configuration (B7) achieving the highest load, strain, and energy absorption. The findings confirm that integrating polyurea coatings with CFRP can effectively delay debonding and significantly improve the reliability and toughness of strengthened RC members, offering a practical solution for more resilient structural retrofitting. Full article

Johne’s disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is endemic in Saudi Arabia and contributes to substantial production losses in small-ruminant herds. This study investigated MAP infection in 388 locally raised small ruminants (151 sheep and 237 goats) using IS900 real-time PCR (qPCR) on fecal samples and indirect ELISA on serum samples. Ziehl–Neelsen (ZN) staining and pathological assessment were applied as supportive tools in necropsied cases. Overall, qPCR detected MAP DNA in 135/388 animals (34.8%), with higher positivity in goats (100/237; 42.1%) than in sheep (35/151; 23.1%). ELISA detected MAP antibodies in 120/388 animals (30.9%), including 90/237 goats (37.9%) and 30/151 sheep (19.8%). Based on clinical examination (presence/absence of clinical signs), qPCR-positive animals were categorized as subclinical (n = 15; 10 goats and 5 sheep) or clinically progressed (n = 120; 90 goats and 30 sheep). Gross and histopathological findings were assessed in a necropsied subset (n = 20; 10 subclinical and 10 clinically progressed), revealing mild focal granulomatous enteritis with scant acid-fast bacilli in subclinical cases and diffuse lepromatous-type granulomatous lesions with abundant bacilli in clinically progressed animals. Genotyping and subtyping were performed on tissue-derived DNA from six necropsied cases using DMC, IS900, and F57 targets, and IS900 sequencing confirmed the circulation of both Type C/II and Type S/I MAP strains. Collectively, these findings demonstrate widespread MAP infection among small ruminants in Saudi Arabia, with higher detection rates and more pronounced pathology in goats, and highlight the genetic heterogeneity of circulating MAP strains. Full article

Accurate cell and nuclei segmentation remains challenging due to the sensitivity of classical graph-cut methods to parameter tuning. While deep learning models like U-Net offer strong performance, they require large annotated datasets and substantial GPU resources. This work presents a cost-effective alternative: a genetic programming (GP) framework that jointly optimizes unary cost functions and regularization parameters for graph-cut segmentation, coupled with automatic seed selection. Evaluation is conducted under two distinct protocols: (1) oracle-guided per-image optimization, establishing upper-bound performance (mean Dice 0.822, IoU 0.733), and (2) true generalization via train/test split, where expressions learned on 50 images are applied to 50 unseen images (mean Dice 0.695, IoU 0.588). The fixed-model generalization still significantly outperforms the baseline graph cut ($+0.158$ Dice, $p<0.001$). Cross-dataset validation on MoNuSeg (H&E histopathology) achieves a Dice score of 0.823 with the fixed GP model, significantly outperforming the baseline (+0.272). This result uses a single fixed model—the best-performing expression from BBBC038 training—applied in a zero-shot manner to MoNuSeg without any retraining or domain adaptation. All 100 images showed non-negative improvement under oracle optimization in the experiments. The method requires no GPU training, runs in 550 s per image for oracle search, and offers interpretable symbolic cost functions. Code and annotations are provided to ensure reproducibility. This approach offers a practical, interpretable alternative in resource-constrained biomedical imaging settings. Full article

Image captioning using deep learning bridges computer vision and natural language processing, enabling machines to generate human-like textual descriptions for images. While significant progress has been made in English, in Arabic, the image captioning field remains under-explored due to the language’s morphological complexity, right-to-left script, and scarcity of annotated datasets. This paper addresses this gap by adapting the BLIP-2 (Bootstrapped Language—Image Pre-training) model for Arabic caption generation, leveraging machine-translated datasets, like Flickr 30k, to overcome resource limitations. BLIP-2 combines a vision transformer (ViT) for image encoding and a CamelBERT large language model (LLM) for text generation, enhanced by a lightweight Querying Transformer (Q-Former) for cross-modal alignment. Despite challenges such as translation artifacts and linguistic nuances, our experiments demonstrate promising results in generating coherent Arabic captions. In short, this study highlights the potential of BLIP-2 for multilingual applications while underscoring the need for native Arabic datasets and further optimization. Ultimately, this work contributes to advancing inclusive artificial intelligence technologies for Arabic-speaking communities, with applications in assistive tools, education, and content creation. Full article

This study proposes a four-dimensional Historical Building Defect Information Modeling (HBDIM) framework designed to support the documentation, diagnosis, and conservation of deteriorated historic stucco elements. The framework integrates multi-source digital documentation techniques, including terrestrial laser scanning (TLS), high-resolution photogrammetry, and automated total station measurements with laboratory-based material diagnostics to create a unified digital environment for defect detection and conservation assessment. The approach was applied to the Baron Empain Palace in Egypt as a representative case study of complex architectural heritage affected by material deterioration. Within the HBDIM workflow, point cloud processing and defect-oriented information modeling were used to identify and spatially localize deterioration features such as cracking, erosion, and material loss. Laboratory investigations—including computed tomography (CT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray fluorescence (XRF)—were conducted to evaluate the effectiveness of calcium hydroxide nanoparticle consolidation treatments and to relate microstructural material behavior to spatially mapped defects within the digital model. Mechanical testing demonstrated a significant improvement in material performance, with treated stucco samples exhibiting an average compressive strength increase of approximately 69.06% compared to untreated specimens. The results demonstrate that integrating digital documentation, defect-oriented modeling, and material diagnostics within a four-dimensional framework provides a robust platform for linking geometric deterioration patterns with material-level conservation performance. By embedding diagnostic data and treatment outcomes within a temporally structured digital model, the HBDIM approach supports preventive conservation strategies, long-term monitoring, and data-driven decision-making in sustainable heritage management. Full article

Numerous studies have shown that overweight and obesity significantly increase the risk of severe illnesses, including type 2 diabetes, hypertension, and knee osteoarthritis. This study aims to develop a generalized mathematical model to manage the growing prevalence of overweight and obesity. We first demonstrate that the model’s solution remains positive and bounded under specific conditions. To determine optimal intervention strategies, we apply Pontryagin’s minimum principle (PMP) to establish necessary optimality conditions. The Forward–Backward Sweeping Method (FBSM) is then used to obtain numerically optimal controls and to demonstrate their effect over a fixed time interval. The results indicate that the proposed approach effectively reduces overweight and obesity while ensuring cost-effectiveness. Full article

This study investigates the shear performance of reinforced concrete (RC) beams strengthened with near-surface-mounted (NSM) carbon fiber-reinforced polymer (CFRP) ropes under ambient and elevated temperature conditions. An experimental program comprising twelve RC beams was conducted, including both normal- and high-strength concrete specimens. The beams were strengthened using CFRP ropes installed at two orientations (45° and 90°) and two spacing configurations (150 mm and 200 mm). Ten specimens were exposed to a temperature of 600 °C prior to shear testing. The experimental results were evaluated against finite element (FE) simulations and shear strength predictions obtained from ACI 440.2R provisions. The FE models demonstrated close agreement with the observed experimental response, whereas ACI 440.2R consistently yielded conservative shear strength estimates, particularly for high-strength concrete beams. The results confirm that inclined CFRP configurations and reduced rope spacing significantly enhance shear capacity, even after severe thermal exposure, with measured strength gains reaching approximately 75% relative to unheated control beams and up to 135% compared to heated control specimen. The findings emphasize the sensitivity of NSM CFRP in terms of strengthening effectiveness to elevated temperature and highlight the limitations of existing design provisions when applied to fire-damaged RC members. Full article

In response to recent advances in computer-aided drug discovery (CADD) enabled by high-performance computing, computational approaches were employed to support and rationalize the investigation of a VEGFR-2-targeted anticancer candidate, combining molecular-level modeling with experimental validation. Initial in silico ADMET profiling and molecular docking were conducted to support the evaluation of drug-like properties and target engagement within a series of para-toluidine-based derivatives (1–14). The most biologically active compound was further evaluated through 100 ns molecular dynamics simulations and comprehensive DFT calculations to investigate binding stability and electronic characteristics. Based on a rational design strategy and supported by computational analyses, the compounds were synthesized and fully characterized using IR, MS, ¹H/¹³C NMR, and elemental analysis. Biological evaluation was performed against HepG-2, MCF-7, HCT-116, and normal WI-38 cells. Mechanistic studies included VEGFR-2 inhibition, wound-healing migration assays, cell-cycle distribution analysis, apoptosis assessment, and caspase-3 activation. Several derivatives exhibited micromolar cytotoxic activity, with compound 14 emerging as the most active against HepG-2 cells (IC₅₀ = 7.84 ± 0.5 µM), showing cytotoxic activity comparable to that of sorafenib (IC₅₀ = 9.18 ± 0.6 µM) and demonstrating favorable selectivity toward normal WI-38 cells (IC₅₀ = 67.75 ± 3.6 µM). Compound 14 showed moderate VEGFR-2 inhibitory activity (IC₅₀ = 0.55 µM), significant suppression of cell migration, pronounced G₀/G₁ cell-cycle arrest, and robust apoptosis induction supported by caspase-3 activation. Molecular docking and MD simulations supported a stable binding mode within the VEGFR-2 active site. This integrated framework highlights compound 14 as a selectively active VEGFR-2-oriented anticancer candidate scaffold with a favorable selectivity profile, supported by experimental and computational analyses, warranting further lead optimization. Full article

Fractional differential equations provide a flexible framework for describing evolutionary processes in complex media, where nonlocality and memory effects play central roles, and classical integer-order models are frequently inadequate to capture these behaviors. In this work, we revisit the time-fractional Harry Dym (HD) evolution equation in the Caputo sense and construct high-precision analytical approximations using the recently developed Tantawy technique (TT). The method generates a rapidly convergent fractional-power series in time without resorting to perturbative assumptions, auxiliary decomposition polynomials, linearization procedures, or integral transforms, and it remains computationally economical even at high approximation orders. Closed, compact expressions are derived up to the fifth-order approximation and can be systematically extended, yielding excellent agreement with the known exact solution of the classical/integer HD model and with approximations obtained via the new iterative method. A detailed error analysis is carried out by computing absolute and maximum residual errors over the entire computational domain, demonstrating the accuracy, stability, and robustness of the TT for the HD-type fractional nonlinear evolution equation. From a physical perspective, the proposed framework offers a reliable tool for modeling nonlinear wave structures in dispersive media with significant memory and, more generally, for treating a broad class of fractional nonlinear wave equations arising in physics and engineering. Full article