Search Results (2,202)

This study explores how Spanish/Catalan bilinguals acquire requests in Greek as a Foreign Language (FL), focusing on the role of proficiency in different communicative contexts. Fifty-four learners of Greek from different proficiency levels and fifty-three native Greek speakers participated in this study. Data was collected via role plays featuring varied social parameters (+/−Power, +/−Social Distance, +/−Imposition). Retrospective verbal reports were also employed to gain insights into learners’ use of requests, providing an overall view of their self-perceptions and pragmatic concerns across different proficiency levels. The findings revealed differences between native and non-native speakers in request types and the number of modifications, highlighting that increased proficiency does not necessarily result in target-like pragmatic performance. Additionally, social parameters clearly influenced learners’ requesting behavior, although their ability to interpret and appropriately respond to these variables developed inconsistently across different contexts and proficiency levels. Ultimately, the findings of this study may contribute to a better understanding of L2 pragmatic development in Greek as an FL and, in turn, inform pedagogical practices aimed at enhancing learners’ pragmatic competence. Full article

This study examines the generalized nonlinear Hunter–Saxton (HS) model: ${\Phi }_{tx}=\Phi {\Phi }_{xx}+\gamma {\Phi }_x^2,\gamma \ne 0,$ that describes the evolution of spatial potential and angular velocity in the vector field of nematic liquid crystals. Closed-form nematicons are derived via the order reduction of the traveling wave ODE. The qualitative structures are analyzed for different values of the nonlinear parameter $\gamma$. The solutions are graphically depicted to discover rich nematicon geometries including parabolic, cuspon, kink, and singular wave structures. A comprehensive dynamic analysis of the reduced nonlinear ordinary system is performed using the phase plane method, which helps to reveal the non-isolated continuity of equilibrium and the role of singular manifolds in shaping the system’s sensitivity and stability. Bifurcation cases are investigated for distinct values of $\gamma$, and various transitions in trajectory geometry and semi-stability features are shown. The novelty appears in the comprehensive integrating of analytic and dynamic characterizations, through global phase and bifurcation analysis, of the generalized HS equation (HSE), which uncovers the control of nonlinear coefficient $\gamma$ in governing the geometry and stability of the nematicons. Also, the analysis confirms the non-chaotic nature of the associated two-dimensional system, compatible with the Poincaré–Bendixson theorem. Full article

Background: Melanoma and triple-negative breast cancer (TNBC) are the most aggressive skin and breast cancers, often diagnosed at late stages with limited treatment options. The melanoma-associated antigen melanotransferrin (MTf) is overexpressed in these solid tumors, where it drives tumorigenesis, progression, and chemoresistance. Its inhibition correlates with tumor regression, making MTf a promising therapeutic target. This study aimed to develop a novel, selectively targeted antibody–drug conjugate (ADC) against MTf-expressing melanoma and TNBC cancer cells using SNAP-tag fusion protein conjugation technology. Methods: We generated an L49(scFv)-SNAP-tag antibody fusion protein engineered through the genetic fusion of a humanized anti-MTf single-chain variable fragment (scFv) with a SNAP-tag fusion protein capable of site-specific self-labelling with O⁶-benzylguanine (BG) modified substrates in 1:1 stoichiometry. Binding and internalization of the conjugate labeled with BG-Alexa 488 (L49(scFv)-SNAP-Alexa488) were assessed by confocal microscopy and flow cytometry in MTf-overexpressing cell lines. Cytotoxicity was evaluated using the cell viability XTT assay after conjugating the SNAP-fusion protein to the potent monomethyl auristatin-F (BG-AURIF). Results: The L49(scFv)-SNAP-Alexa488 conjugate demonstrated specific binding and internalization into MTf-positive melanoma and TNBC cells. The corresponding ADC, L49(scFv)-SNAP-Linker-AURIF, exerted potent, antigen and dose-dependent cytotoxicity, with IC₅₀ values in the nanomolar range (4.77–34.43 nM). Conclusions: We successfully generated a novel SNAP-tag-based ADC that selectively eliminates MTf-overexpressing tumor cells. This proof-of-concept highlights MTF’s value as a therapeutic target and demonstrates that a smaller-format, non-cleavable linker SNAP-tag-based ADC can achieve potent nanomolar cytotoxicity, supporting further development of MTF-targeted immunotherapies for melanoma and TNBC. Full article

Background: Shoulder instability imposes a substantial burden in U.S. military populations, yet epidemiology and outcomes reporting is heterogeneous. This study aims to quantify the epidemiology of shoulder instability among U.S. active-duty servicemembers and to report operative management patterns and outcomes. Methods: A systematic review was performed by searching MEDLINE, EMBASE, Scopus, Cochrane, and SPORTDiscus through 1 August 2025. Eligible studies enrolled U.S. active-duty servicemembers with clinical and/or radiographic evidence of instability. After a single comprehensive search with uniform inclusion criteria, studies were assigned to two prespecified cohorts: (1) epidemiology (incidence, directionality, risk factors) and (2) operative management/outcomes (procedure distribution, failure, complications, return to duty [RTD] and return to sport [RTS]). Incidence was pooled as a person-years–weighted fixed-effect estimate; directionality proportions were meta-analyzed with random-effects (logit-transformed) models among patient-level, unidirectional cases. Results: Forty-nine studies were included (epidemiology, n = 8; outcomes, n = 41). Three epidemiologic datasets (42,310 events; 20,472,363 person-years) yielded a pooled military incidence of 2.07 per 1000 person-years (95% CI, 2.05–2.09). Among unidirectional cases (n = 916 shoulders), anterior instability comprised 83.9% (95% CI, 70.5–91.9) and posterior the remaining 16.1% (95% CI, 8.1–29.5). Outcome series most commonly reported arthroscopic Bankart repair (n = 933 shoulders), bony augmentation (e.g., Latarjet/Bristow; n = 700), posterior labral repair (n = 649), combined repairs (n = 511), and open Bankart (n = 442). Weighted mean failure ranged 4.7–23.6%; complications 5.2–10.9%; and reoperations 5.3–17.7%. RTD ranged 50.0–84.7% and RTS 4.8–75.0%. Conclusions: Shoulder instability in U.S. servicemembers occurs at rates exceeding population-based civilian estimates, with a relatively greater share of posterior and combined patterns. Operative outcomes vary substantially across procedures. Full article

(1) Background: In the Sudano-Sahelian zone of Cameroon, which is affected by drought and forest decline, Vachellia nilotica leaves and seeds are fodder for livestock. (2) Methods: A provenance and progeny study on growth performance and heritability of V. nilotica was carried out to provide a reliable database for tree selection, improvement programs, and the creation of future forested areas in this region. Open-pollinated seeds from 120 mother trees (10 half-sib families per provenance) representing twelve provenances, 50–100 km apart, were used for a progeny trial near Maroua, the Far North region of Cameroon. The experimental design was a Fisher block. (3) Results: The results reveal significant differences among provenances only for the number of leaves, and the variability was marked by coefficients of variation ranging from 0.24−0.63. Narrow-sense heritability was measured, varying from 0.01 ± 0.009 to 0.74 ± 0.02, and genetic gain reached 21.83 at the selection intensity of 5% for the number of leaves per plant. The phenotypic coefficient of variation varied between 14% and 90%. Half-sib families were classified into three subgroups using hierarchical ascending classification, and provenances were grouped into five groups using principal component analysis. (4) Conclusions: These results could contribute to initiating tree selection, but more provenances, longer-term experiments, and molecular genetic testing are needed to complement these nursery-level observations. Full article

Lysosomal storage disorders (LSDs) are a group of rare inherited diseases caused by mutations in the genes encoding the proteins involved in normal lysosomal functions, leading to an accumulation of undegraded substrates within lysosomes. Among the most prominent clinical features are neurological impairment and neurodegeneration, arising from widespread cellular dysfunction. The development of powerful and reliable animal model systems that can in vivo recapitulate human LSD pathologies is critical for understanding disease mechanisms and advancing therapeutic strategies. In this study, we identified the Drosophila melanogaster orthologs of human LSD-related genes using the DIOPT tool and performed tissue-specific gene silencing along the brain–midgut axis via the use of GAL4/UAS and RNAi combined technologies. Transgenic fly models presented key features of human LSD pathologies, including significantly shortened lifespans and a progressive locomotor decline that serves as a measure for neuromuscular disintegration, following age- and sex-dependent patterns. These phenotypic parallels in pathology strongly support the functional relevance of the selected orthologs and underscore the value of Drosophila as a versatile in vivo model system for advanced LSD pathology research, offering state-of-the-art genetic tools for molecularly dissecting disease mechanisms and providing cutting-edge novel platforms for high-throughput genetic and/or pharmacological screening, moving towards development of new therapeutically beneficial drug-based regimens and mutant gene-rescue schemes. Full article

Background: Global declines in immunisation rates and a resurgence in measles pose a threat, even in countries like Australia that have achieved elimination status. National coverage in Australia is measured at static timepoints, so it is unclear at what age children received their vaccines. This may permit the emergence of immunity gaps, leaving children susceptible to measles between those reporting timepoints. Methods: A cross-sectional retrospective analysis was conducted using routinely collected data from the Australian Immunisation Register for children residing in Hunter New England Local Health District (HNELHD), New South Wales, born from 1 January 2015 to 1 June 2019 as a quality improvement initiative. Coverage, age at immunisation, and on-time immunisation were described by demographic, local geographic and age variables. Reverse survival analysis was conducted to determine the timing of achieving 95% MCV2 coverage. To ensure the cultural integrity of the research, an Aboriginal researcher co-led the design, analysis and interpretation of results. Results: The analysis included 53,390 children. Measles coverage exceeded the national and international target of 95% MCV2 coverage, with coverage in Aboriginal children surpassing national rates for all children. Pockets of low coverage were identified in several smaller geographic areas and subpopulations. Median age of MCV1 receipt was 375 days (IQR: 369–390 days), and MCV2 was 560 days (IQR: 551–583 days). More recent birth cohorts had earlier immunisation. On-time immunisation rates were high, and most children receiving measles immunisation late were still immunised within six months of the schedule date. The 95% MCV2 coverage threshold was achieved at 1582 days of age. Conclusions: Robust measles immunisation coverage and timeliness were found in HNELHD, Australia. Timeliness data analysis is a useful adjunct to static coverage data in understanding immunisation protection. Improving immunisation data availability, accessibility, and timeliness offers potential to better inform targeted public health activity. Full article

The New Jersey Safe Schools Program (NJSS) provides required training for secondary school career–technical education work-based learning (WBL) supervision, allowing certified teachers to supervise students in school-sponsored work placements. During each training’s virtual live session day, a new activity for teachers to use to connect the U.S. Substance Abuse and Mental Health Services Administration’s (SAMHSA) “Eight Dimensions of Wellness” model (8DW) to individual young workers was conducted. NJSS implemented an optional “Eight Dimensions of Young Worker Wellness” activity with 67 volunteer participants (44% response rate) in February–November 2024. Using Mentimeter, teachers were given a student worker scenario and asked how aspects of the scenario pertained to each of the 8DW (emotional, environmental, financial, intellectual, occupational, physical, social, spiritual). A qualitative, inductive content analysis of open responses collected via Mentimeter was conducted. Most teachers selected emotional and social dimensions of 8DW when asked to select the two most important for young workers to incorporate into their work lives. This new NJSS activity encouraged teachers to examine different aspects of their own health, and potentially they could then apply it to the health, safety, and wellness of their students and co-workers, as a proactive approach to promote comprehensive wellness. Full article

This study aimed to evaluate, through finite element analysis (FEA), the biomechanical behavior of edentulous maxillary overdentures supported on 2, 3, and 4 implants with conometric connections, and to determine the minimum implant number that maintains stresses within physiological limits. A 3D finite element model of a resorbed edentulous maxilla was generated from CT images and processed in ANSYS v19.0. Subsequently, six models were simulated according to implant number (2, 3, or 4) and cortical bone thickness (0.5 mm or 1 mm). Conical connection implants and cobalt–chromium-reinforced overdentures with Equator attachments were modeled. Bilateral axial loads were applied and Von Mises equivalent stresses were calculated for implants and abutments, while maximum and minimum principal stresses were analyzed in bone. Results showed that the highest deformation and stress concentrations were observed in the two-implant models, with trabecular stresses ranging from 6.5 to 8.4 MPa, exceeding the 5 MPa safety threshold. In contrast, both three- and four-implant models maintained trabecular stresses below 3 MPa, while keeping cortical bone stresses within physiological limits. The three-implant tripod configuration demonstrated a comparable stress distribution to the four-implant models. From a biomechanical perspective, overdentures supported on four implants with 1 mm cortical thickness showed the most favorable performance. Nevertheless, the three-implant model represented a biomechanically acceptable and potentially cost-effective alternative, suggesting its viability as a simplified clinical option that warrants further investigation. Full article

Background: Severe (FIGO grade 3b & c) placenta accreta spectrum (PAS) is potentially a life-threatening condition due to catastrophic haemorrhage at delivery. Consequently, interventional radiology (IR) techniques are often employed to prevent massive blood loss, but this is not always readily available, is costly, and can cause significant morbidity, including distal limb ischaemia due to thrombus formation. We believe that internal iliac ligation under direct vision is a safe option to control bleeding. We sought to evaluate the short- and long-term outcomes relating to this technique compared to IR. Methods: This is a mixed-methods cohort study of women with severe PAS who underwent hysterectomy with either surgical devascularisation, as part of the Soleymani and Collins (SAC) technique, or IR insertion of internal iliac balloon catheters, in a UK tertiary referral centre for PAS between 2011 and 2022. Only women with intraoperative diagnosis of very severe PAS (FIGO stage 3b & c) were included in this study. Results: Of the 22 women invited to participate in the long-term component of the study, 59% agreed. Women in the surgical devascularisation group experienced no adverse short or late sequelae related to internal iliac arterial ligation. Pelvic devascularisation (11 patients, 41%) demonstrated a reduction in median estimated blood loss, 1600 millilitres vs. 2500 millilitres in the IR balloon catheter group (p = 0.04). Conclusions: We have demonstrated that the SAC technique for surgical devascularisation is a safe method for achieving haemorrhage control during caesarean hysterectomy for severe PAS. It also appears to be at least as effective at haemorrhage control as IR balloon occlusion of the internal iliac vessels. Full article

Bone is a structurally complex and dynamic tissue that plays a crucial role in mobility and skeletal stability. However, conditions such as osteoporosis, osteoarthritis, trauma-induced fractures, infections, and malignancies often necessitate the use of orthopedic and dental implants. Despite significant progress in implant biomaterials, challenges such as bacterial infection, inflammation, and loosening continue to compromise implant longevity, frequently leading to revision surgeries and extended recovery times. Smart coatings have emerged as a next-generation solution to these problems by providing on-demand, localized therapeutic responses to microenvironmental changes around implants and promoting bone regeneration. Such coatings can minimize antibiotic resistance by enabling controlled, stimulus-triggered drug release. Although the idea of using pH-sensitivity as a tool to make smart coatings is not a new thought, there are no options currently good enough to enter clinical studies. This review provides a comprehensive overview of recent advances in pH-sensitive polymers, hybrid composites, porous architectures, and bioactive linkers designed to dynamically respond to pathological pH variations at implant sites. By investigating the mechanisms of action, antibacterial and anti-inflammatory effects, and roles in bone regeneration, it is shown that the ability to provide time-dependent drug release for both short-term and long-term infections, as well as keeping the environment welcoming to the bone cell growth and replacement, is not an easy goal to reach, even with a fully biocompatable, non-toxic, and semi-biodegradable (one that releases the drug, but does not fade away) coating material compound. Reviewing all available options, including their functions and failures, finally, emerging trends, translational barriers, and future opportunities for clinical implementation are highlighted, underscoring the transformative potential of bioresponsive coatings in orthopedic and dental implant technologies. Full article

In recent years, pervious oyster shell habitat (POSH) units have been developed and deployed as part of living shoreline projects in Northeast Florida. POSH units are modular artificial oyster reef structures made from cement and recycled oyster shells. POSH units aim to improve oyster recruitment, attenuate wave energy, trap sediment, and restore salt marsh habitat. Previous studies demonstrated the units’ ability to attract oyster larvae and reduce shoreline bed stress in some areas. This paper further explores the effect of POSH unit placement on bed stress under boat wake conditions using large-eddy simulations (LES). Results indicated that certain POSH unit arrangements may be preferable; a small overlap between segments may help block flow and reduce associated stresses, while a chevron pattern may benefit sites subject to oblique waves. However, even these more “optimized” configurations resulted in bed stresses with similar orders of magnitude when compared to more linear arrangements. Understanding how POSH units affect bed stress and potential erosion patterns can help restoration stakeholders design future living shorelines with POSH units or other similar structures. Full article

In this paper, we present an integrative framework based on Evolutionary Stackelberg Game Theory to model the strategic interaction between a physician, acting as a rational leader, and a heterogeneous population of treatment-sensitive and treatment-resistant breast cancer cells. The model incorporates ecological competition, evolutionary adaptation, and spatial heterogeneity, enabling prediction of tumor progression under clinically relevant treatment protocols. Using tumor volume data obtained from breast cancer-bearing mice treated with Capecitabine and Gemcitabine, we estimated treatment and subject-specific parameters via the GEKKO optimization package in Python. Benchmarking against classical tumor growth models (Exponential, Logistic, and Gompertz) showed that while classical models capture monotonic growth, they fail to reproduce complex, non-monotonic behaviors such as treatment-induced regression, rebound, and phenotypic switching. The game-theoretic approach achieved superior alignment with experimental data across Maximum Tolerated Dose, Dose-Modulation Adaptive Therapy, and Intermittent Adaptive Therapy protocols. To enhance adaptability, we integrated reinforcement learning (RL) for both single-agent and combination chemotherapy. The RL agent learned dosing policies that maximized tumor regression while minimizing cumulative drug exposure and resistance, with combination therapy exploiting dose diversification to improve control without exceeding total dose budgets. Incorporating reaction diffusion equations allowed the model to capture spatial dispersal of sensitive (cooperative) and resistant (defector) phenotypes, revealing that spatially aware adaptive strategies more effectively suppress resistant clones than non-spatial approaches. These results demonstrate that evolutionarily informed, spatially explicit, and computationally optimized strategies can outperform conventional fixed-dose regimens in reducing resistance, lowering toxicity, and improving efficacy. This framework offers a biologically interpretable tool for guiding evolution-aware, patient-tailored cancer therapies toward improved long-term outcomes. Full article

Baltimore’s historic row-home neighborhoods face escalating risks to energy, heat, and durability under intensifying climate stress. This study develops a Housing-Performance Atlas that quantifies multi-hazard performance for eight representative archetypes using DesignBuilder/EnergyPlus Version 7.3.1.003, under Baltimore TMY3 boundary conditions. Performance is evaluated across the following four adaptation domains: energy use intensity, passive survivability during 72 h outage events, roof overheating exposure (>150 °F exceedance hours), and material service life derived from ISO 15686 and synthesized into Lean and Full Deficit Indices for comparative resilience ranking. Results show that EUI ranged from 46.7 to 67.6 kBtu ft⁻²·yr⁻¹, survivability from 0 to 23 h, and roof temperatures exceeded 150 °F for 150–210 h, shortening roof service life by up to 10 years. Composite Lean and Full Deficit Indices ranged 7.8–92.4, ranking Model 5 (end-unit, flat roof, two-story with basement) as the most resilient configuration and Model 8 (end-unit, pitched roof, three-story above-grade) as the least resilient due to compounded overheating and energy losses. Heat-related domains accounted for nearly 70% of overall resilience deficits, confirming thermal safety and roof reflectivity as retrofit priorities. The Housing-Performance Atlas establishes a reproducible diagnostic framework linking simulation, service life, and resilience metrics to guide cost-effective, climate-responsive retrofits in Baltimore’s aging urban housing stock. Full article

Use of the upper limb to engage in everyday activities is a key indicator of functional recovery of stroke survivors. In addition to functional capacity, personal and environmental factors contribute to real-world upper limb use post-stroke. We aimed to combine data from the experience sampling method (ESM), a method used to capture real-time engagement in daily activities, with accelerometry, an objective measurement of arm use, to evaluate arm use behaviours of adult stroke survivors living in real-world environments. Thirty mild–moderately impaired stroke survivors and 30 age-standardized healthy individuals were monitored over 7 days, using accelerometers on both wrists and four ESM beeps per day to capture individual experiences in daily activities. Stroke survivors showed significantly lower use of the affected arm across all activity domains compared to the non-dominant arm of healthy participants and reported perceived lower skill and higher challenge levels. Physical context, motor capabilities and activity type were associated with affected arm use behaviour, with greater use observed during social settings and in physically demanding tasks. These findings demonstrate that combining ESM with accelerometry provides a novel, ecologically valid framework to capture and interpret the interplay between capacity, context, and behaviour in everyday life. This approach offers opportunities to design personalized, context-aware rehabilitation strategies that promote meaningful functional reintegration after stroke. Full article