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Incidence of tuberculosis in patients with immune-mediated diseases undergone biological therapy: A 10-year observational study in a high-burden region of northeastern Brazil
Biological therapies are critical in the management of Immune-Mediated Diseases (IMDs), yet their use is linked to adverse effects, including an elevated risk of Tuberculosis (TB), a significant health issue in endemic regions like Brazil. This study aimed to assess the incidence of TB among patients with IMDs in rheumatology, gastroenterology, and dermatology who received biological therapy in Pernambuco between 2013 and 2023. A total of 8,623 patients were analyzed, with 90.7% diagnosed with rheumatologic diseases, 5.6% with gastroenterological diseases, and 3.7% with psoriasis. In the descriptive analysis, frequency distributions and medians with interquartile ranges were reported, and Relative Risk (RR) was calculated to compare tuberculosis occurrence across IMD groups. The overall TB incidence was 2.1%, highest in gastroenterological patients (4.7%) compared to rheumatologic (2.0%) and psoriasis patients (1.3%) with a risk ratio (RR) of 2.4 for the group of gastroenterological diseases (p < 0.001). No significant differences in TB frequency were detected before (1.16%) or during (0.97%) the use of biological therapy, nor among drug classes, except for a slightly higher incidence with infliximab (2.6%). The absence of differences between the other anti-Tumor Necrosis Factor (anti-TNF) drugs and other cytokine inhibitors suggests that TB incidence might be influenced by environmental exposure in endemic regions. Pulmonary TB was the predominant form (80.8%), and pleural TB emerged as the most frequent extrapulmonary manifestation. The results underscore the need for extensive regional studies to elucidate TB risks in IMD patients and refine treatment guidelines for immunobiological therapies.
Subpixel-registered dual-mode imaging enables label-free inference of mitochondria in living cells
Fluorescence microscopy remains indispensable for specific organelle imaging but suffers from photobleaching and phototoxicity. Here, we introduce a strong physics-constrained deep learning strategy to generate virtual fluorescence images of mitochondria directly from quantitative phase imaging. By constructing a dual-mode system that captures quantitative phase and fluorescence images in situ with subpixel registration, we impose a strong physical prior that ensures native subpixel alignment and data fidelity. This native spatial constraint significantly reduces the burden on the neural network, enabling high-confidence, label-free identification of mitochondria from phase data alone. Once trained, the model bypasses the need for fluorescent labeling, eliminating photodamage and facilitating long-term dynamic studies. The trained network exhibits remarkable generalization capability, making it highly practical for routine use and paving the way for truly nondestructive, high-content imaging of subcellular structures in living cells.
Infrared thermal imaging to determine temperature parameters of dengue vector habitats across ecological regions of Nepal: a pilot feasibility study
Abstract Dengue is a major vector-borne disease in Nepal, driven by container-breeding Aedes mosquitoes that thrive in domestic, urban settings. Its risk is increasing from the lowland Terai to the Hill and Mountain regions due to urbanisation and global warming. Practical and innovative approaches are needed to better understand the impact on Aedes mosquito habitats that are the main targets for vector control. We conducted a pilot feasibility study to characterise Aedes aegypti and Aedes albopictus breeding sites, examine physicochemical parameters (total dissolved solids, pH, salinity, dissolved oxygen), and explore the utility of infrared thermal imaging as a novel tool for measuring temperature parameters of habitats across distinct ecological regions. We found that plastic containers, tin/metal items, and rubber tyres were common breeding sites. The dengue vectors Ae. aegypti and Ae. albopictus were identified in a variety of container types across most locations. Overall, there was reasonable agreement between the thermal camera and standard thermometer, although the camera recorded approximately 1 °C lower and showed divergence at higher temperatures. Most aquatic habitat temperatures were within an optimal mosquito breeding range (mid-20s to low 30s °C) and lower than non-breeding site temperatures. The breeding site water temperatures in the Terai region were ~ 4 °C higher than the Mid-Hill and Mountain regions. Aquatic habitat temperatures were also found to be significantly correlated with dissolved oxygen. Thermal imaging case studies provided key visual insights into varying temperatures in complex Aedes microclimates. Notably, inner rubber tyre temperatures remained relatively stable despite significant external temperature fluctuations and external tyre temperatures exceeding 50 °C. Thermal imaging shows promise for the field characterisation of mosquito breeding sites, but it is not interchangeable with standard thermometry without qualification, including calibration and uncertainty analysis.
Evaluating the cultural alignment of multilingual LLMs in typical Japanese workplace scenarios
While current evaluations of LLM cultural alignment predominantly rely on static benchmarks in Western contexts, their ability to navigate generative, high-context socio-pragmatic demands in non-Western environments remains critically underexplored. This study investigates how multilingual LLMs adapt to the Japanese workplace—a stringent stress-test environment characterized by strong high-context communication norms and rigid honorific conventions—using Hofstede’s six cultural dimensions as a heuristic framework. We evaluated five state-of-the-art LLMs (LLM-jp, Phi, Llama, Qwen, and GLM) through a large-scale crowdsourced human evaluation. Based on 1,718 valid evaluator sessions, native Japanese raters assessed model outputs to generate a holistic Japanese Workplace Cultural Alignment Score (JWCAS). To dissect the underlying communicative strategies, we paired this with a three-layer diagnostic sub-score analysis (Linguistic Form, Socio-Cultural Values, and Social Action). Our results reveal that leading multilingual models (Phi and GLM) achieved overall JWCAS scores comparable to, or significantly higher than, the native Japanese model (LLM-jp). Crucially, our sub-score analysis demonstrates that holistic evaluation metrics can obscure deep pragmatic deficits: while LLM-jp overfits to surface-level linguistic politeness (Layer 1), it shows critical weaknesses in socio-cultural values (Layer 2) and context-aware social strategies (Layer 3). In contrast, leading multilingual models demonstrate balanced competence across all layers. These findings suggest that true cultural competence requires moving beyond native linguistic mastery, highlighting the necessity of multi-dimensional diagnostic frameworks for cross-cultural AI alignment.
Excitation and imaging of GHz surface acoustic waves in Al1−xScxN grown on SiC by molecular-beam epitaxy
Scandium incorporation significantly boosts the piezoelectric properties of wurtzite AlN thin films. Synthesis of wurtzite Al1−xScxN thin films on SiC, although underexplored, can lead to benefits in terms of epitaxial quality and performance of radio frequency (RF) devices such as surface-acoustic-wave (SAW) filters. In this work, we grow 200 nm-thick Al1−xScxN thin films (0≤x≤0.18) without buffer layers by plasma-assisted molecular-beam epitaxy (PAMBE) on semi-insulating 6H- and 4H-SiC substrates. The epitaxial thin films exhibit both (0001) surface orientation and in-plane epitaxial alignment across the whole investigated composition range. A full-width at half-maximum of 0.3° is recorded for the Al0.82Sc0.18N film in the 0002 x-ray rocking curve. Consistent with the well-established enhancement of the effective electromechanical coupling coefficient keff2 by ternary alloying, we observe a tenfold improvement of keff2 for SAW devices operating above 6 GHz in the Al0.82Sc0.18N film compared to the AlN binary film grown and processed under consistent conditions. In addition, we visualize the impact of possible film cracking on SAW propagation utilizing atomic-force microscopy mapping with nanometer-scale spatial resolution. Our report demonstrates that PAMBE-grown Al1−xScxN/SiC yields high epitaxial quality and is a promising platform for GHz SAW technology, with potential extensions to other RF devices that require submicrometer thickness.
Milk yield and immune protein profiles in colostrum and milk of indigenous syrian Golani and Golani × Friesian crossbred cows
PAP_NER: A large-scale vietnamese administrative named entity recognition corpus and hybrid deep learning architecture
Named Entity Recognition (NER) is fundamental for automating administrative document processing in digital government systems. However, Vietnamese NLP research faces a critical infrastructure gap: existing datasets focus on generic information extraction (news, medical) rather than domain-specific administrative text. We present PAP_NER, the first large-scale, gold-standard Vietnamese administrative NER corpus comprising 162,801 sentences with 205,807 entity annotations across five entity types critical for e-Government workflows: Agency (CQ), Legal Document (VBPL), Object (ĐT), Datetime (NG), and Quantity (SL). The dataset was constructed through a rigorous human-in-the-loop annotation pipeline, achieving an inter-annotator agreement of κ = 0.85. We demonstrate PAP_NER’s value through comprehensive benchmarking of an established hybrid deep learning architecture, PhoBERT-CRF, which couples monolingual Transformer embeddings (PhoBERT) with Conditional Random Fields for structured prediction. PhoBERT-CRF achieves 97.95% Micro F1-score on the PAP_NER test set, significantly outperforming established baselines: BiLSTM+CRF (+2.01%), multilingual XLM-RoBERTa (+2.52%), and pure Transformer approaches (+0.44%). Ablation analysis reveals that the CRF layer provides statistically significant improvements for structurally complex entities (VBPL: + 0.96%, p < 0.05, McNemar’s test). We release PAP_NER publicly (DOI: 10.5281/zenodo.18044019 ) under Creative Commons BY 4.0 license to support reproducibility and enable further research in Vietnamese administrative NLP. This work establishes a foundational dataset and methodology for addressing the Vietnamese government NER gap, with implications for low-resource language NLP research.
Spin-selective nonlinear imaging in real and Fourier space via chiral metasurfaces
Nonlinear chiral metasurfaces represent a compelling platform for spin-selective light–matter interactions and multidimensional optical information processing. However, existing designs are typically restricted to single-parameter manipulation or rely on intricate supercell architectures, making simultaneous and independent control of multiple wavefront degrees of freedom challenging. Here, we present a streamlined design paradigm for nonlinear chiral metasurfaces, in which spin-selective and independent modulation of amplitude and phase can be achieved by adjusting merely two geometric parameters of a single chiral meta-atom. As a proof of concept, we implement a multifunctional metasurface by arranging spatially segregated enantiomeric structures, experimentally demonstrate spin-selective dual-channel nonlinear imaging in real and Fourier space under left- and right-circularly polarized fundamental excitation. Each polarization channel simultaneously generates a near-field grayscale image (real space) and its corresponding far-field holographic reconstruction (Fourier space). This work paves the way toward multifunctional, high-efficiency, and ultracompact nonlinear photonic devices.
Importance of overlapping network nodes in influence spreading
Cyclodextrin inclusion complexes enhance the solubility and anti-virulence activity of metronidazole against uropathogenic Proteus mirabilis
Proteus mirabilis is a major uropathogen implicated in catheter-associated urinary tract infections and infection-induced urolithiasis, often exhibiting multidrug resistance. Improving the solubility and bioactivity of existing drugs represents a promising pharmaceutical strategy to overcome these challenges. In this study, inclusion complexes of metronidazole with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD) were prepared using physical mixing and kneading methods. Complexes were characterized using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). In vitro release behaviour, minimum inhibitory concentration (MIC), and effects at sub-MIC levels on motility, urease-associated phenotype, and biofilm formation were evaluated. β-CD and HP-β-CD systems demonstrated improved release profiles compared to metronidazole alone. While MIC values remained within the mg/mL range, HP-β-CD complexes showed reduced MIC relative to aqueous metronidazole, achieving a four-fold reduction in MIC. At sub-MIC concentrations, β-CD and HP-β-CD formulations were associated with significant suppression of motility, reduced urease-associated phenotypes, and inhibition of biofilm formation. Molecular docking suggested spatial compatibility between metronidazole and cyclodextrins, though mechanistic conclusions remain predictive. These findings indicate that cyclodextrin-based complexation enhances physicochemical performance of metronidazole and may support adjunctive anti-virulence modulation in P. mirabilis. Further mechanistic and in-vivo studies are required to validate translational relevance.
High-capacity data transmission with 24-bit orbital angular momentum multiplexing under dynamic scattering media
When orbital angular momentum (OAM) beams pass through scattering media, mode coupling and interference occur, distorting the phase front and converting the beam into a random speckle pattern, so high capacity and fidelity communication becomes challenging. To address this, we propose a few-shot learning scheme to demonstrate an unprecedented highest capacity 16-bit and 24-bit fractional OAM multiplexing communication system under complex environments. By decomposing the full classification task into 16 or 24 binary subtasks, the system requires only 20 000 and 30 000 training classes, corresponding to 30.5% and 0.18% of the total class space, respectively. This approach significantly reduces the required data and computational resources. Experimentally, OAM multiplexed beams are scattered by a rotating ground-glass diffuser to generate speckle patterns. After training on a small subset of superimposed OAM states, the model learns to extract latent features from the speckles and accurately predicts each OAM channel across the entire set. Additionally, the use of a space-to-depth mechanism for low-resolution OAM recognition enhances the accuracy of the OAM channels impacted by the environment. The system achieves average channel identification accuracies of 99.82% (16-bit) and 94.45% (24-bit). To validate the scheme, color images are successfully transmitted in both static and dynamic scattering environments. In short, this work provides a clever approach for extremely high-capacity OAM communication in harsh environments.
Factors associated with psychological resilience, COVID-19-related anxiety, and COVID-19 vaccine hesitancy among academic professionals
Helminth-derived stefin-1 selectively reduces leukemic cell viability and promotes apoptosis in U937 cells
Leukemia remains a challenging hematological malignancy, particularly due to treatment resistance and the limited availability of therapies that selectively target cancer cells. Helminth-derived cysteine protease inhibitors (stefins) are mainly known for their roles in host–parasite interactions, but their effects on cancer cells have not been well explored. In this study, we investigated the biological activity of recombinant Fasciola gigantica Stefin-1 (rFgStefin-1) in the human U937 leukemic cell line. Treatment with rFgStefin-1 reduced cell viability in a dose- and time-dependent manner, with an IC₅₀ of approximately 11 µM at 48 h. In contrast, normal peripheral blood mononuclear cells (PBMCs) showed minimal changes under the same conditions. Flow cytometry analysis demonstrated increased apoptotic cell populations together with mitochondrial membrane depolarization following rFgStefin-1 treatment. At the molecular level, rFgStefin-1 treatment was associated with an increased BAX/BCL-2 ratio, increased cleaved caspase-3 expression, reduced AKT-associated signaling, and enhanced PARP cleavage. These findings were supported by both qRT-PCR and Western blot analyses. Overall, these results suggest that rFgStefin-1 promotes apoptosis in leukemic cells while exerting limited effects on normal cells under the tested conditions. Further studies are required to clarify the underlying molecular mechanisms and to evaluate the effects of rFgStefin-1 in additional leukemia models and in vivo systems.
Hidden polymorphic landscape in two-dimensional ZnO
Two-dimensional ZnO has long been described by a graphitic honeycomb model, yet growing experimental evidence suggests a more complex structural landscape. Here, we use physics-constrained random structure search and first-principles calculations to explore the low-energy configurations of monolayer ZnO. We find that the planar graphitic phase is not the ground state. Instead, ZnO favors a double-layer honeycomb structure stabilized by interlayer Zn–O bonds, which appears graphitic in projection but is chemically distinct from a planar sheet. We further uncover a family of metastable triangular–tetrahedral polymorphs located 40–56 meV/atom above the ground state. These phases are dynamically stable and arise from coupled electrostatic and coordination disproportionation, which redistributes electrostatic repulsion and splits distorted tetrahedral sites into trigonal and tetrahedral building blocks. These findings recast polar non-van der Waals semiconductors as competing structural landscapes shaped by polarity, coordination, and electrostatics.
Astrocyte activation and gliosis contribute to brain-wide neuroinflammation following experimental subarachnoid hemorrhage
Outcomes of proximal humeral chondroblastoma treated with intralesional curettage, electrocauterization of the cavity and bone grafting: A retrospective study
Objectives This study aimed to evaluate the 7-year outcomes of proximal humeral chondroblastoma treated with intralesional curettage, electrocauterization of the cavity and bone grafting in pediatric patients. Methods A total of 17 patients diagnosed with proximal humeral chondroblastoma who underwent surgical treatment consisting of intralesional curettage, cavity electrocauterization, and bone grafting at our center between January 1, 2008, and January 1, 2018, were retrospectively enrolled. All patients received postoperative splint immobilization for four weeks and were followed up for a minimum of seven years. Tumor recurrence was evaluated based on clinical manifestations and radiographic X-ray examination. Clinical outcomes included functional performance assessed using the Musculoskeletal Tumor Society (MSTS) score and the Quick Disabilities of the Arm, Shoulder and Hand (Quick DASH) scale, as well as postoperative complications. Results In total, 17 patients with proximal humeral chondroblastoma were enrolled in our study, including 10 males and 7 females, with a mean age of 10.9 ± 1.8 years old (range from 8 to 14 years). Among these 17 cases, there were 6 cases with lesions extending through the epiphyseal plate, and 11 cases with lesions located inside the epiphysis. During follow-up, 1 patient suffered reoperation due to tumor recurrence. Shortening of the affected upper limb occurred in 9 patients (52.9%), which was significantly associated with a young age(P = 0.012). The mean shortening was 1.2 ± 0.9 cm compared with the contralateral limb. The overall mean postoperative MSTS was 27.5 ± 1.4 points, with no significant difference between observed the limb shortening group (27.3 ± 1.4) and the non-shortening group (27.8 ± 1.4,P = 0.550). The overall Quick DASH score averaged 4.8 ± 3.9 (0–15.9), and no statistically significant difference was detected between the shortening group (5.3 ± 4.5) and the non-shortening group (4.3 ± 2.8; P = 0.452). Conclusions Intralesional curettage, cavity electrocauterization and bone grafting is an optional treatment for children with proximal humeral chondroblastoma but still has a risk of recurrence. Shortening of the affected upper limb is a common complication, which is possibly associated with young age but has no impact on the final functional outcomes. Level of Evidence Level IV, retrospective case series.
Redirecting a Native Ene‐Reductase Toward Desaturation With Reverse Enantioselectivity
ABSTRACT Chiral enones are valuable motifs in synthetic intermediates and bioactive molecules, driving significant interest in biocatalysis. Although recent enzymatic desaturation strategies for substituted cyclohexenones provide efficient and highly enantioselective synthetic routes, none offer complementary stereoselectivity. To address this gap, we introduce a stereocomplementary biocatalytic system based on an old yellow enzyme (OYE), XenA from Pseudomonas putida . Although XenA natively catalyzes the reduction of electron‐deficient alkenes and exhibits negligible desaturation activity, protein engineering redirected its catalytic function toward desaturation, ultimately yielding a variant that accommodates a range of cyclohexanones with 85%–99% ee and 32%–98% yield. Remarkably, the optimal variant (XenA_4) possesses 46 mutations and exhibits an 11°C increase in melting temperature over the wild type. Mechanistic studies revealed that the unique dimeric structure of the enzyme is pivotal in controlling stereoselectivity by modulating the substrate‐binding orientation.
Erratum: “An electrothermally actuated high-power MOEMS optical switch with a state-latching mechanism” [Appl. Phys. Lett. <b>128</b> , 173303 (2026)]
A comprehensive benchmark of deep learning architectures for appearance-based gaze estimation
SPP1 promotes cisplatin resistance in cervical cancer by regulating KRAS expression
Background Chemotherapy resistance is a major treatment issue for cervical cancer (CC), contributing to high morbidity and mortality. This study identifies key molecular drivers of CC progression and cisplatin (DDP) resistance, focusing on secreted phosphoprotein 1 (SPP1). Methods Differentially expressed genes (DEGs) were identified from TCGA-CC and GSE46857 datasets. Protein-protein interaction network analysis and topological ranking determined candidate genes. SPP1 expression was evaluated in CC cell lines using qPCR and Western blotting. Cisplatin-resistant CC cells were used to examine SPP1’s role in drug resistance. Functional assays assessed cell proliferation, apoptosis, migration, and invasion. Results Bioinformatics analysis identified SPP1 as a hub gene upregulated in CC. SPP1 expression was higher in CC and DDP-resistant cells. Silencing SPP1 inhibited cell growth and enhanced apoptosis, while overexpression had the opposite effects. Silencing SPP1 enhanced DDP sensitivity, while overexpression reduced DDP cytotoxicity. Mechanistically, SPP1 positively correlated with KRAS expression, and KRAS modulation partially reversed SPP1’s effects on DDP resistance. Conclusion SPP1 is upregulated in CC and DDP-resistant cells, promoting tumor progression and chemoresistance via KRAS. Targeting the SPP1-KRAS axis may help overcome chemotherapy resistance in CC.