Search Results (584)

Background: Recent transcriptomic studies classify small-cell lung cancer (SCLC) into molecular subtypes driven by ASCL1, NEUROD1, POU2F3, and YAP1. This study evaluated an immunohistochemistry (IHC)-based subtyping framework using real-world data and assessed its ability to predict chemoimmunotherapy outcomes. Methods: Proteomic expression profiles were quantified by IHC in 100 patients with SCLC. Clinicopathological trajectories and overall survival (OS) were analyzed using a parsimonious multivariate Cox model designed to mitigate overfitting. Results: Significant subclonal heterogeneity was captured by co-dominant hybrid phenotypes, including SCLC-AN (9%) and SCLC-AP (5%). In the treatment-adjusted, parsimonious multivariate analysis, individual continuous biomarker expressions showed an independent association with ASCL1 percentage (HR = 1.011, p = 0.017). Traditional extensive-stage disease (HR = 3.801, 95% CI: 1.669–8.657, p = 0.001) and synchronous bone metastases (HR = 1.968, 95% CI: 1.074–3.604, p = 0.028) remained the only robust clinical predictors of poor OS. When adjusted for therapeutic interventions, first-line chemoimmunotherapy showed a strong protective numerical trend, reducing mortality risk by 49% (HR = 0.512, p = 0.060). Within the immunotherapy subgroup (n = 19), the NE-low group had a 100% response rate and a numerically longer median overall survival than the NE-high group (49.4 vs. 21.4 months; log-rank p = 0.080). Conclusions: Our pilot evaluation provides a clinically feasible routine IHC framework for characterizing subclonal mosaicism in SCLC. Full article

Fungal contamination and mycotoxins remain important hazards in cereal, nut, oilseed, and processed-food chains. For grain handlers, processors, storage facilities, quality-assurance laboratories, and technology developers, the practical challenge is not only detection but determining when an AI-enabled optical output is sufficiently documented to support accepting, holding, sorting, or referring material for confirmatory analysis. This critical narrative review, supported by structured evidence appraisal, examines artificial intelligence (AI)-enabled hyperspectral imaging (HSI) for fungal and mycotoxin risk management. The focused evidence map comprises a combined 20-study evidence map, including 17 spectral-imaging studies and three contextual non-imaging near-infrared studies addressing aflatoxins, fumonisins, deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA), fungal status, and co-contamination; no patulin-specific AI-HSI study met the defined corpus criteria. Most evidence remains laboratory-based, with controlled contamination, limited independent validation, incomplete transfer testing, or no line-level demonstration. The review proposes the preliminary Food–AI Deployment-Readiness Framework (F-AIDRF), a non-regulatory appraisal tool covering analytical validity, algorithmic robustness, explainability and auditability, transferability and maintenance, operational feasibility, and decision integration. Applied descriptively, F-AIDRF is intended to reveal missing evidence, not to certify technologies. For food-industry readers, it offers a practical vocabulary for comparing screen-sort-confirm systems before investment, pilot testing, or regulatory-facing use. Full article

Accurate channel estimation in millimeter-wave MIMO-OFDM systems is hindered by limited pilot resources and the high sensitivity of physical priors to propagation conditions. This paper proposes PERL, a physics-enhanced residual learning framework that integrates ray-tracing (RT) priors with deep neural networks to refine coarse RT-based estimates. Unlike direct channel reconstruction, PERL learns a residual correction atop the RT baseline, with the correction magnitude adaptively gated according to noise level and RT reliability, thereby relying more on physical priors under low SNR and exploiting pilot observations for refinement at high SNR. The framework leverages a Transformer-based multimodal attention mechanism to deeply fuse sparse pilot observations, path-level propagation features (delay, angle, power, and phase), and scene-level statistical descriptors, enabling physical constraints and data-driven refinement to interact effectively. Experiments on a 28 GHz urban macro-cellular MIMO-OFDM scenario demonstrate that PERL achieves an overall NMSE of −28.82 dB, outperforming the RT baseline by 5.30 dB and the MMSE estimator by over 20 dB, with notably larger gains under non-line-of-sight conditions where the RT prior is less accurate. Link-level evaluations further confirm improved error vector magnitude and maintained bit/block error rates relative to the RT baseline, validating that the proposed physical-data collaborative paradigm not only enhances estimation accuracy but also preserves communication reliability, while offering a promising foundation for future detection-aware and integrated-sensing-and-communication optimizations. Full article

Background: In advanced cancer care, routine clinical assessment often focuses on symptoms, treatment tolerance, and disease status, while spiritual well-being remains insufficiently explored despite its relevance to quality of life (QoL). Standardized patient-reported tools may help identify spiritual and existential vulnerability in patients receiving palliative treatment. This study evaluated the EORTC QLQ-SWB32 as a structured spiritual well-being assessment tool in advanced cancer care through its cultural adaptation and clinical validation among Romanian patients. Furthermore, it evaluated the tool’s feasibility and explored the association between spiritual well-being and QoL in individuals receiving palliative systemic therapy. Methods: Following EORTC Quality of Life Group guidelines, the QLQ-SWB32 was translated and pilot-tested with ten cancer patients. A prospective, cross-sectional observational study was then conducted at the Regional Institute of Oncology in Iași, Romania. Over six months, 42 adult patients with metastatic or locally advanced inoperable malignancies undergoing palliative systemic therapy were enrolled. Participants completed the EORTC QLQ-SWB32 and EORTC QLQ-C15-PAL questionnaires, while sociodemographic and clinical variables were collected using structured case report forms. Results: The translated instrument showed good linguistic clarity and clinical acceptability during pilot testing. The study cohort was predominantly aged 40–64 years (52.38%) and was socio-culturally homogeneous, with all patients identifying as Romanian and most as Eastern Orthodox (92.85%). The Relationship with God/the Divine (RSG) domain showed a stronger association with QoL in male patients than in female patients, particularly in subsequent treatment lines. In the subsequent-line subgroup, residential environment reached statistical significance (p = 0.021), with a stronger RSG–QoL correlation among rural residents. Age-related inversion patterns in the RSG–QoL association were also observed across treatment lines. Conclusions: Spiritual well-being assessment may provide clinically relevant patient-reported information in advanced cancer care. The Romanian EORTC QLQ-SWB32 demonstrated feasibility, linguistic clarity, and clinical validity as a structured assessment tool. The association between the Relationship with God/the Divine domain and QoL varied according to sex, age, residential environment, and treatment trajectory, supporting the integration of standardized spiritual assessment into individualized palliative oncology care. Full article

Background/Objectives: Rapid optical assessment of freshly excised basal cell carcinoma (BCC) specimens may shorten the interval between excision and margin evaluation. This prospective pilot study estimated the diagnostic performance of ex vivo line-field confocal optical coherence tomography (LC-OCT) for detecting residual BCC at lateral surgical margins, using histopathology as the reference standard. Methods: Fifty-five clinically suspicious lesions from 48 patients were examined at two centers. Results were analyzed for the complete cohort and for a post-training inclusion phase comprising 32 lesions from 31 patients. Overall lesion-level consensus classifications were recorded separately from classifications of the four clock-face quadrants. Lesions with a negative overall LC-OCT assessment and at least one non-evaluable quadrant were classified as indeterminate and excluded from the primary lesion-level analysis. Thirteen lesions also underwent exploratory ex vivo fusion confocal microscopy (evFCM). Results: In the inclusion phase, 125 of 128 quadrants were evaluable. Thirteen true-positive, 106 true-negative, 2 false-negative, and 4 false-positive quadrant results yielded 86.7% sensitivity, 96.4% specificity, and 95.2% accuracy. At the lesion level, 2 of 32 results were indeterminate. Among the remaining 30 lesions, LC-OCT yielded 5 true-positive, 22 true-negative, 2 false-negative, and 1 false-positive results, corresponding to 71.4% sensitivity, 95.7% specificity, and 90.0% accuracy. The evFCM analysis was descriptive because the subset was small and nonconsecutive. Conclusions: Ex vivo LC-OCT showed promising specificity and overall accuracy for assessing lateral BCC margins after training. The limited number of margin-positive lesions, indeterminate results, clustered quadrant data, and absence of systematic deep-margin imaging require cautious interpretation. LC-OCT should not replace histopathological margin assessment on the basis of the present data. Full article

Introduction: The Awareness/Acceptance/Action Model (AAAM) was initially developed by one of the authors to explore stigma and prejudice towards people living with HIV/AIDS. In the present study, the AAAM was examined for its personal and professional relevance to people affected by the Troubles, 30 years of sectarian conflict in Northern Ireland. When unchecked, judgmental or reactive attitudes can undermine intentions to consistently deliver services in line with professional standards and human rights. Methods: Despite a devolved, power-sharing government and steps to address longstanding political and religious grievances, cultural sensitivities and animosity remain on both sides of the divide. A university in Northern Ireland recruited 11 practice teachers and 18 social work students, who participated in one of four focus groups. Mindfulness principles and techniques were used to allow participants to visualise “the other” before exploring how prejudice might impact personal and professional interactions. Thematic analysis of focus group transcripts was conducted using Braun and Clarke to assess the presence and nature of labelling, stereotyping, out-grouping and discriminating against people perceived as “the other”. Findings: Given the potential differences in identity, background, and experiences of social work practitioners and service users, it is important that we critically reflect on how we serve people based on direct or intergenerationally transmitted encounters. The AAAM was then piloted in undergraduate social work degree programmes and shared with practice teachers. Feedback confirmed that it offers a theoretical framework to promote anti-oppressive practice and critical reflection during professional social work training. Using Mindfulness techniques to visualise “the other” prompted participants to listen well and look deeply at the origins of their prejudices or fear, and how these could lead to biased interactions with service users. Full article

Venetoclax-based therapy is effective in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but tumor lysis syndrome (TLS) risk necessitates a resource-intensive five-week dose ramp-up with intravenous hydration, frequent laboratory monitoring, and clinic-based observation, creating logistical barriers particularly in community settings. We conducted a single-center, IRB-approved retrospective pilot study of 30 patients with CLL/SLL who underwent a cytoreduction-adapted, IV-free outpatient venetoclax ramp-up with reduced laboratory monitoring between 2023 and 2026. All patients received cytoreductive therapy—predominantly single-agent BTKi—and met protocol-defined low-tumor-burden criteria (ALC < 20 × 10⁹/L, lymph nodes < 5 cm, no splenomegaly, CrCl > 45 mL/min) before venetoclax initiation. Venetoclax was self-administered at home with laboratory monitoring reduced to a single approximately 12-h post-dose assessment per dose-escalation week. Median age was 71 years; 80% had received ≥2 prior therapy lines, and 37% had high-risk cytogenetics. Monitoring compliance was 100%. No laboratory or clinical TLS, IV hydration, hospitalizations, dose interruptions, treatment discontinuations, or deaths occurred during ramp-up. These pilot data support the feasibility and early safety of simplified outpatient venetoclax initiation in adequately cytoreduced patients and warrant prospective multicenter validation. Full article

The value of informatization lies not only in expanding urban digital infrastructure, but also in reshaping firm behavior through improvements in the information environment. Using China’s smart city pilot program as a quasi-natural experiment and a sample of Chinese A-share listed firms, this study examines whether urban-level informatization affects corporate ESG performance. The staggered difference-in-differences estimates show that smart city pilots significantly improve firms’ ESG performance, and the result remains robust after a range of endogeneity checks and robustness tests. Mechanism analyses provide evidence consistent with the proposed external monitoring and internal governance channels. Specifically, smart city pilots are associated with stronger monitoring by capital-market participants and improved internal governance conditions, in line with investor attention theory and organizational information processing theory. The effect is more pronounced for firms whose executives have environmental backgrounds, firms in heavily polluting industries, and firms located in regions with stronger environmental regulation. Further tests show that ESG improvements induced by informatization increase both short-term profitability and long-term market valuation. These findings reveal how urban informatization promotes corporate ESG performance and show that ESG improvements can help firms align social value with economic value. Full article

Background: Diffuse large B-cell lymphoma (DLBCL) with TP53 abnormalities, corresponding to the LymphGen A53 molecular subtype, represents a biologically high-risk group associated with primary resistance to standard R-CHOP therapy. Epigenetic sensitization using hypomethylating agents may enhance chemosensitivity in this setting. We prospectively evaluated the clinical activity and safety of a molecularly adapted DAC-R-CHOP regimen in newly diagnosed A53-DLBCL. Methods: In this single-center prospective pilot cohort study, 70 consecutive patients with newly diagnosed DLBCL underwent targeted next-generation sequencing using a 60-gene panel with integrated copy number variation analysis. Six patients (8.5%) were classified as the A53 subtype. All patients received one cycle of standard R-CHOP. From cycle 2 onward, A53 patients received decitabine (10 mg/m² IV, days 1–5) prior to R-CHOP (DAC-R-CHOP), for a total of six cycles. The primary endpoint was complete metabolic response (CMR) according to Lugano 2014 criteria. Exact 95% confidence intervals (CI) were calculated. Results: The median age of the A53 cohort was 65 years. CMR was achieved in all six patients (100%; 95% CI, 54–100%). At a median follow-up of 6 months, all patients remained alive in confirmed CMR. Grade III–IV hematologic toxicity occurred in all cases. Febrile neutropenia developed in 100% of patients, requiring mandatory G-CSF support and anti-infective therapy; no treatment-related mortality or permanent dose reductions were observed. Two patients (33%) experienced gastrointestinal bleeding related to local tumor lysis, which was managed conservatively without protocol discontinuation. Conclusions: In this prospective molecularly stratified pilot cohort, integration of decitabine into front-line immunochemotherapy showed promising clinical activity in A53-DLBCL, albeit at the cost of substantial hematologic toxicity requiring intensive supportive care. Given the small sample size, short follow-up, and absence of a comparator arm, these findings should be considered hypothesis-generating and warrant validation in larger multicenter phase II studies with integrated translational biomarker analyses. Full article

The modern multi-domain battlespace increasingly demands cost-effective, persistent platforms for Forward Air Control (Airborne) (FAC(A)) and Close Air Support (CAS) missions. While utilizing Commercial Derivative Aircraft (CDA) presents a viable alternative to high-maintenance military assets, the specific aerodynamic, ergonomic, and cognitive workload limitations encountered during the transition across the civil–military “airworthiness seam” remain a significantly underexplored gap in contemporary aerospace literature. To address this gap, a comprehensive empirical flight test campaign was executed on the LX7-135 turboprop to evaluate its tactical mission suitability. Employing the Cooper–Harper Handling Qualities Rating and Bedford Workload scales, and guided by military specifications (MIL-HDBK-516C, MIL-F-8785C), the study systematically assessed the aircraft’s pure performance, unaugmented flight dynamics, and human–machine interface during simulated combat scenarios, including dynamic 9-Line briefings and kinetic “Box Pattern” delivery profiles. Flight test data indicated 12 “SATISFACTORY” parameters, highlighting climb rates, extended endurance, and heavily damped short-period and Dutch roll modes optimal for target tracking. Conversely, the evaluation identified 4 “UNSATISFACTORY” and 10 “TOLERABLE” deficiencies—chiefly a single-door egress bottleneck, restricted stick clearance, degraded longitudinal static stability, and the absence of secure tactical communications. Although these constraints elevated pilot cognitive workload during multi-axis tasks, the LX7-135 demonstrates potential suitability for further development for the FAC(A) role, subject to the successful implementation and subsequent flight-test verification of the identified critical engineering modifications and specialized training syllabi. Full article

Assessing mosquito vector competence for emerging arboviruses, including the underlying determinants of infection, is a foundational line of investigation towards understanding arbovirus transmission dynamics and vector–virus interactions. We developed a novel quantitative immune gene array that measures the relative expression of 22 immune genes with functional representation across five major immune pathways using quantitative reverse-transcriptase polymerase chain reaction. Homologous primers were developed for Culex tarsalis, Cx. quinquefasciatus, and Ae. aegypti mosquitoes. As an initial pilot test for this array, Cx. tarsalis and Ae. aegypti mosquitoes were orally challenged with Rift Valley fever virus (RVFV) MP12 strain. Midguts, legs/wings, and salivary glands were harvested at 3 and 7 days post-challenge. Differential gene expression was measured against Rpl32 as a housekeeping gene. This assay was sensitive enough to generate results for single mosquito midgut and salivary gland tissues, providing an initial snapshot of the types of gene expression patterns that can be observed for two mosquito species infected with MP12. This new tool will be broadly applicable for assessing mosquito immune profiles for arbovirus infection across major immune genes in five key pathways, as well as generating comparable results across mosquito and arbovirus systems. Full article

Women with polycystic ovary syndrome (PCOS) have a substantially increased risk of endometrial cancer (EC), yet the biological mechanisms underpinning this association, to support future prevention and therapeutics, remain incompletely understood. Insulin-like growth factor (IGF)-associated signaling has been implicated, but existing evidence is conflicting. In this pilot translational study, serum IGF1 and IGFBP-3 were measured in women with PCOS (n = 12 for IGF1 and n = 6 for IGFBP-3) and controls (n = 24 for IGF1 and n = 7 for IGFBP-3). Pooled serum, stratified by IGF bioactivity, was applied to human EC cells to further assess effects on cell viability, cell cycle distribution, and downstream signaling. Computational analysis of publicly available endometrial cancer datasets was used to contextualize experimental findings. Serum IGF1 and IGFBP-3 levels did not differ significantly between PCOS and control groups. However, pooled PCOS serum was associated with increased EC cell viability, altered cell cycle progression and PI3K/AKT/mTOR signaling compared with control serum in this exploratory model. Pharmacological inhibition of IGF1R partially attenuated these effects, suggesting that IGF-associated pathways may contribute but are unlikely to act in isolation. In silico analysis identified frequent alterations in PI3K/AKT/mTOR-related genes in EC, consistent with pathway-level vulnerability rather than IGF1-specific dependence. These findings suggest that PCOS serum contains factors that are associated with increased EC cell viability and altered signaling pathways with partial involvement of IGF signaling; however, these findings should be interpreted cautiously given the exploratory pooled-serum design, small subgroup sizes, and use of a single EC cell line. However, multiple metabolic and hormonal pathways are likely to contribute. Larger, better-controlled studies incorporating insulin, sex steroids, and multiple EC models are required before causal inferences can be made. Full article

The paper analyzes the evolution and strategy development for sustainable community-based ecotourism (CBET) in the commune of Hoa Bac in Central Vietnam. It is based on a pilot project carried out from 2019 to 2025 within the scope of a larger research project funded by the German Federal Ministry of Research, Technology and Space (BMFTR) as part of the research line ‘Sustainable Urban Regions’. As a key component of the overall research approach, the goal of this pilot project along the Cu De River valley in the vicinity of the city of Da Nang has been a culturally adapted and ecologically sensitive tourism model that leads to income and socio-economic improvement, environmental protection and a decentralized low-impact infrastructure. The results of six years of qualitative longitudinal participatory research based on community workshops, interviews and surveys, direct observations as well as participatory field activities show how transformations in natural, cultural, human, social, financial and built capitals have shaped the transition from resource-dependent livelihoods to a diversified ecotourism economy. By mobilizing and empowering the local community, partly belonging to the Co Tu ethnic minority, sustainable development emerged not from isolated interventions but from a structured process of interlinked development strategies including cultural revitalization, environmental preservation, locally adapted agroforestry, skills and capacity development, cooperative governance, decentralized infrastructure, and income diversification. The study demonstrates that stakeholder and community empowerment, appropriately designed governance models (in this case the establishment of a tourism cooperative), targeted capacity development and knowledge transfer can strengthen the resilience and long-term sustainability of ecologically sound and culturally adaptive community-based tourism initiatives. Overall, the lessons learned from the research in Hoa Bac contribute to designing and implementing a holistic approach to CBET in rural settings. Full article

We study indoor visible light positioning (VLP) in a fully three-dimensional setting under thermal noise and signal-dependent shot noise. Existing shot-noise-aware least-squares (LS) VLP methods largely rely on a fixed receiver height, so their key simplifications break down when the vertical coordinate is unknown. We derive a 3D likelihood-inspired surrogate, lift the nonlinear geometry into a weighted LS form, and add a geometry-aware regularizer that restores approximate consistency among redundant lifted variables. To make the iterative solver reliable in sparse layouts, we introduce room-feasible projection, consistent pilot reconstruction, clipped frozen weights, and damped objective-accepted updates. Each inner step remains a closed-form 4 × 4 linear solve. In deterministic synthetic simulations of an 8 × 8 × 3 m room with layouts containing 4, 9, and 16 light-emitting diodes (LEDs), high- and low-power regimes, and 400 test samples per scenario, the stabilized solver removes the catastrophic sparse-layout failures observed for the tested LS-family baselines and retains a 14×–23× runtime advantage over the nonlinear baseline. The nonlinear baseline often attains lower mean error in sparse and moderate layouts; the contribution here is the resulting speed–tail-control trade-off within the fixed-orientation line-of-sight model. The resulting estimator is intended for synthetic 3D VLP simulations; hardware validation is outside the present study. Full article

Background and Objectives: Faricimab, the first bispecific antibody targeting VEGF-A and angiopoietin-2, has demonstrated durable efficacy in pivotal phase 3 trials for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Real-world data on treatment-naïve patients managed with fixed-interval maintenance protocols, particularly from South-Eastern Europe, remain limited. This pilot study evaluated 24-month outcomes of intravitreal faricimab in treatment-naïve nAMD and DME, using a standardized four-injection loading phase followed by fixed every-16-week (Q16W) maintenance. Materials and Methods: This study conducted a retrospective, observational, single-center pilot cohort study of 20 consecutive treatment-naïve eyes (9 nAMD, 11 DME). All patients received four monthly loading injections followed by a fixed every-16-week (Q16W) maintenance schedule, supplemented by discretionary additional injections for residual or recurrent disease activity (215 injections total; mean 10.75 ± 0.79 per patient; range 9–12). Primary outcomes were changes in central foveal thickness (CFT) and best-corrected visual acuity (BCVA; Snellen lines with ETDRS letter equivalents) at months 4 and 24. Prespecified secondary analyses included bootstrap 95% confidence intervals, a linear mixed-effects model with a time × disease-group interaction, Bayesian credible intervals with weakly informative priors, false-discovery-rate (FDR) correction, and a minimum detectable effect-size analysis. Results: All 20 eyes completed 24-month follow-up. In nAMD, mean CFT decreased by 186.9 ± 71.9 µm (35.9%; bootstrap 95% CI 148.1–236.0; p < 0.001; d = 2.60), and BCVA improved by 3.89 ± 0.78 Snellen lines (~19 ETDRS letters; 95% CI 3.44–4.33; p < 0.001; d = 4.97). In DME, CFT decreased by 197.7 ± 65.7 µm (39.3%; 95% CI 162.5–237.3; p < 0.001; d = 3.01), and BCVA improved by 4.55 ± 1.04 lines (~23 ETDRS letters; 95% CI 4.00–5.09; p < 0.001; d = 4.39). All 20 eyes (100%) achieved ≥ 3 Snellen lines gain and ≥20% CFT reduction; 80% reached final BCVA ≥ 7 lines. A linear mixed-effects model showed a significant time effect (p < 0.001) but no time × group interaction (CFT p = 0.84; BCVA p = 0.51), indicating concordant trajectories across diseases. Bayesian analysis with weakly informative priors yielded posterior P(|d| > 0.8) ≥ 0.99 for all primary outcomes. After FDR correction, all pre-specified primary comparisons remained significant. The minimum detectable effect size with the realized sample sizes (Cohen’s d ≈ 0.66 combined, 1.07 nAMD, 0.94 DME at 80% power) was substantially below all observed effect sizes. No ocular or systemic adverse events were recorded. Conclusions: In this small, single-center, treatment-naïve pilot cohort, a fixed Q16W faricimab maintenance schedule with discretionary additional injections was associated with durable anatomical and functional improvements over 24 months in both nAMD and DME, with no adverse events recorded across 215 injections. Given the limited sample, these findings should be regarded as hypothesis-generating. The high responder rates likely reflect the cohort’s substantial baseline visual impairment (mean baseline BCVA ~20/120–20/200), which provides greater absolute capacity for measurable gain than in higher-acuity registration trial populations. These pilot data support fixed-interval faricimab as a logistically feasible candidate strategy in resource-constrained settings and should be confirmed in larger multicenter cohorts using standardized ETDRS acuity assessment. Full article