Search Results (201)

This study presents an experimental investigation of the influence of dopant type and calcination temperature on BaTiO₃-based piezoceramics synthesized by a solid-state calcination process. The effects of Mn, Nb, La, and Ce dopants on the structural, morphological, and piezoelectric characteristics of powders calcined at 1000 °C and 1100 °C were systematically evaluated. In addition, two co-doped BaTiO₃ compositions, namely Mn–Nb and La–Nb, calcined at 1000 °C, were investigated in order to assess the combined effect of acceptor–donor and donor–donor doping strategies on microstructural evolution and structural stability. The synthesized powders were characterized by scanning electron microscopy (SEM), particle size analysis, energy-dispersive X-ray spectroscopy (EDS), elemental mapping, and X-ray diffraction (XRD), in comparison with a commercial BaTiO₃ reference powder. The piezoelectric response was assessed by correlating the structural modifications induced by doping with the estimated piezoelectric coefficient d₃₃, calculated as a function of the tetragonality ratio (c/a) and further correlated with the crystallite size. The results reveal significant variations in grain growth, dopant distribution, and crystallographic stability, highlighting the critical role of dopant chemistry and calcination temperature in tailoring the functional properties of BaTiO₃ for piezoelectric applications. Full article

Background/Objectives: Psoriatic disease is a systemic inflammatory condition associated with increased cardiometabolic risk, but the impact of contemporary systemic therapies and narrowband ultraviolet B (NB-UVB) phototherapy on vascular and systemic inflammatory markers remains incompletely characterized. We aimed to systematically synthesize prospective evidence on treatment-associated changes in vascular inflammation and systemic inflammatory biomarkers in adults with moderate-to-severe psoriatic disease. Specifically, we evaluated changes assessed by 18F-FDG PET/CT imaging and circulating biomarkers following biologic therapies or NB-UVB phototherapy. Methods: We systematically searched MEDLINE, Embase, Web of Science, Scopus, and CENTRAL from inception to 31 January 2026 for prospective interventional and observational studies in adults with psoriasis or psoriatic arthritis treated with biologic agents targeting TNF-α, IL-12/23, IL-17, or IL-23, or with NB-UVB phototherapy. Eligible studies were required to report serial assessments of vascular inflammation by 18F-FDG PET/CT (typically aortic target-to-background ratio) and/or systemic inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, TNF-α, GlycA, or hematologic indices such as the neutrophil-to-lymphocyte ratio) over at least 8 weeks of follow-up. We imposed no language restrictions and included only full-text, peer-reviewed prospective studies. Risk of bias was evaluated using RoB 2 for randomized trials and ROBINS-I for nonrandomized studies. Random-effects meta-analyses were prespecified for outcomes reported by at least two clinically comparable studies; however, because of substantial heterogeneity in reporting and methodology, effect estimates were summarized using a structured narrative synthesis. Results: Thirteen prospective studies (n ≈ 900 adults, published 2015–2025) met inclusion criteria, including four studies with serial 18F-FDG PET/CT imaging and one additional PET/CT study providing baseline observational data on vascular inflammation, as well as eight biomarker-focused prospective cohorts. Across randomized mechanistic trials and observational studies, biologic therapies reduced aortic target-to-background ratio by approximately 6–12% over 12–24 weeks (e.g., mean change from 2.42 to 2.18 with TNF-α inhibition and from 2.51 to 2.20 with IL-17 blockade), and no study reported worsening of PET-derived vascular indices under effective systemic treatment. Biologic and other systemic therapies produced concordant reductions in hs-CRP (typically by 30–50%), IL-6, TNF-α, GlycA, and blood-count-derived indices including neutrophil-to-lymphocyte ratio, with biomarker improvements frequently paralleling reductions in cutaneous disease activity and cardiometabolic risk markers. Two NB-UVB cohorts demonstrated significant hs-CRP reductions of roughly 20–30% and modulation of vitamin D-related inflammatory proteins, suggesting systemic anti-inflammatory effects, although these changes appeared less pronounced than with biologic therapy and were not accompanied by vascular imaging. Conclusions: Contemporary systemic psoriasis therapies, particularly biologic agents targeting the IL-23/Th17 axis and TNF-α, are associated with consistent reductions in aortic vascular inflammation and broad improvements in systemic inflammatory biomarkers, whereas NB-UVB phototherapy confers more modest but measurable systemic anti-inflammatory effects, although the current evidence does not allow differentiation between individual biologic classes in terms of magnitude of effect. Although reductions in vascular and systemic inflammatory markers were observed across therapies targeting TNF-α, IL-12/23, IL-17, and IL-23, the small number of mechanistic imaging studies and absence of head-to-head comparisons do not allow robust differentiation between biologic classes or support a uniform class effect. The convergence of imaging and biomarker data reinforces psoriasis as a clinically relevant model of inflammation-driven atherosclerosis and supports the concept that effective control of psoriatic inflammation may contribute to cardiovascular risk modification, highlighting the need for integrated cardiovascular risk assessment in routine care. However, the imaging evidence base remains limited to four small mechanistic PET/CT studies with relatively short follow-up, which constrains the strength and generalizability of conclusions regarding vascular inflammation. Larger, adequately powered, event-driven prospective trials with standardized imaging and biomarker endpoints are needed to determine whether these vascular and systemic anti-inflammatory effects translate into reduced cardiovascular events in psoriatic disease; because of methodological and reporting heterogeneity across the 13 included studies, these conclusions are based on a structured narrative synthesis rather than a formal quantitative meta-analysis. PROSPERO registration number: CRD420261296646. Full article

Environmental monitoring is essential for smart agriculture, renewable energy assessment, and climate-aware farm management. However, deploying autonomous sensing platforms in rural environments remains challenging because of energy constraints, communication reliability, and real-time processing requirements. This paper presents a modular, solar-powered environmental monitoring platform integrating LTE-M communication and TinyML-enabled edge sensing. The proposed system adopts a dual-microcontroller architecture that combines an Arduino Nano 33 BLE for real-time sensor acquisition and edge processing with an Arduino MKR NB 1500 dedicated to low-power wide-area communication. The platform integrates temperature, humidity, atmospheric pressure, rainfall, wind, and light sensors within a scalable framework. Two monitoring stations were deployed in rural regions of Romania to evaluate communication robustness, sensing stability, and energy autonomy. Field results demonstrated reliable LTE-M connectivity (4306 received signal strength indicator [RSSI] samples; mean $-75.51$ dBm) and strong agreement with a regional weather station, with mean deviations of −0.71 °C (temperature), $4.98\%$ (humidity), and a stable pressure offset of $-9.58$ hPa attributable to altitude differences. Despite a total system cost of €315, the platform achieved measurement performance comparable to that of professional meteorological stations while maintaining long-term solar-powered operation. The proposed architecture provides a scalable and cost-effective solution for distributed smart agriculture and environmental monitoring applications. Full article

Spirocyclic compounds are experiencing a research surge due to their unique 3D structure, offering enhanced pharmacological, industrial, and material applications. They are increasingly used in medicinal chemistry to improve drug-like properties, such as solubility and target binding, and are also being utilized for advanced material applications, including electronics and photonics. In this communication, 3-(4-hydroxyphenyl)-1′,3′,6-trimethyl-2′H,3H,4H-spiro[furo[3,2-c]pyran-2,5′-pyrimidine]-2′,4,4′,6′(1′H,3′H)-tetraone was prepared via a two-stage transformation including a tandem Knoevenagel–Michael reaction and NBS-induced cyclization. At the first stage, a previously unknown ionic scaffold, morpholin-4-ium 5-((4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)(4-hydroxyphenyl)methyl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate was also isolated. Structures of the newly synthesized compounds were established by ¹H and ¹³C NMR, IR spectroscopy, high-resolution mass spectrometry, and elemental analysis. Full article

Background: Neuroblastoma (NB) progression is influenced by metabolic and redox adaptations. The polyol pathway, driven by aldose reductase (AKR1B1) and sorbitol dehydrogenase (SORD), is activated in hyperglycemic conditions, while detoxification of lipid peroxidation products such as 4-hydroxynonenal (4-HNE) involves carbonyl reductase 1 (CBR1) and AKR1B1. A systematic characterization of these enzymes under distinct metabolic and oxidative challenges in NB is currently lacking. Methods: Human neuroblastoma LAN-5 and SH-SY5Y cells were exposed to hyperglycemic medium to assess polyol pathway regulation, and to exogenous 4-HNE to model aldehyde-induced oxidative stress. Protein expression and enzyme activities were quantified. Cells were treated with Sorbinil or rutin during stress exposure, and viability was analyzed in 2D and 3D models. Results: Hyperglycemia increased AKR1B1 activity and sorbitol accumulation, indicating polyol pathway activation in NB cells. Both NB cell lines displayed an incomplete HNE-detoxifying enzyme profile, with absence of ALDH1A1 and AKR1C3 expression. Exposure to 4-HNE reduced NB cell viability both in 2D and 3D models. Pharmacological inhibition of AKR1B1, but not of CBR1, exacerbated 4-HNE-mediated cytotoxicity. Conclusions: While hyperglycemia stimulates the polyol pathway, aldehyde detoxification by AKR1B1 supports resistance to 4-HNE toxicity, demonstrating that AKR1B1 activity is essential to counteract HNE toxicity, and its impairment may increase the susceptibility of NB cells to oxidative damage. Full article

The proliferation of Internet of Things (IoT) devices has created unprecedented security challenges characterized by resource constraints, heterogeneous network architectures, and severe class imbalance in attack detection datasets. This paper presents a comprehensive benchmark evaluation of five Generative Adversarial Network (GAN) architectures for energy-aware intrusion detection: Standard GAN, Progressive GAN (PGAN), Conditional GAN (cGAN), Graph-based GAN (GraphGAN), and Wasserstein GAN with Gradient Penalty (WGAN-GP). Our evaluation framework introduces novel energy-normalized performance metrics, including Accuracy-per-Joule (APJ) and F1-per-Joule (F1PJ), that enable principled architecture selection for energy-constrained deployments. We propose an optimized WGAN-GP architecture incorporating diversity loss, feature matching, and noise injection mechanisms specifically designed for classification-oriented data augmentation. Experimental results on a stratified subset of the BoT-IoT dataset (approximately 1.83 million records) demonstrate that our optimized WGAN-GP achieves state-of-the-art performance, with 99.99% classification accuracy, a 0.99 macro-F1 score, and superior generation quality (MSE 0.01). While traditional classifiers augmented with SMOTE (i.e., Logistic Regression and CNN1D-TCN) also achieve 99.99% accuracy, they suffer from poor minority class detection (77.78–80.00%); our WGAN-GP improves minority class detection to 100.00% on the reported test split (45 of 45 attack instances correctly identified). Furthermore, WGAN-GP provides substantial efficiency advantages under our energy-normalized metrics, achieving superior accuracy-per-joule performance compared to Standard GAN. Also, a cross-dataset validation across five benchmarks (BoT-IoT, CICIoT2023, ToN-IoT, UNSW-NB15, CIC-IDS2017) was implemented using 250 pooled test attacks to confirm generalizability, with WGAN-GP achieving 98.40% minority class accuracy (246/250 attacks detected) compared to 76.80% for Classical + SMOTE methods, a statistically significant 21.60 percentage point improvement ($p<0.0001$). Finally, our analysis reveals that incorporating diversity-promoting mechanisms in GAN training simultaneously achieves best generation quality AND best classification performance, demonstrating that these objectives are complementary rather than competing. Full article

Lead-free transparent ferroelectric ceramics with integrated opto-electro-mechanical functionalities are pivotal for next-generation multifunctional devices. In this study, K_0.48Na_0.52NbO₃-xLa₂O₃ (KNN-xLa, x = 0.005 − 0.04) ceramics were fabricated via a conventional solid-state route to investigate the La³⁺-induced multiscale structural evolution and its modulation of optical and electrical properties. La³⁺ substitution drives a critical structural transition from an anisotropic orthorhombic phase (Amm2) to a high-symmetry pseudocubic-like tetragonal phase (P4mm) for x ≥ 0.025, characterized by minimal lattice distortion (c/a = 1.0052). This enhanced structural isotropy, coupled with submicron grain refinement (<1 μm) driven by ${\mathrm{V}}_{\mathrm{A}}^{\prime }$-mediated solute drag, effectively suppresses light scattering. Consequently, a high-transparency plateau (T₇₈₀ ≈ 53–58%, T₁₇₀₀ ≈ 70–72%) is achieved for 0.025 ≤ x ≤ 0.035. Simultaneously, the system undergoes a crossover from normal ferroelectric (FE) to relaxor (RF) state, governed by an FE–RF boundary at x = 0.015. While x = 0.005 exhibits robust piezoelectricity (d₃₃ ≈ 92 pC/N), the x = 0.015 composition facilitates a transitional polar state with large strain (0.179%) and high polarization (P_m ≈ 33.3 μC/cm², P_r ≈ 15.8 μC/cm²). Piezoresponse force microscopy (PFM) confirms the domain evolution from lamellar macro-domains to speckle-like polar nanoregions (PNRs), elucidating the intrinsic trade-off between optical transparency and piezoelectricity. This work underscores La³⁺ as a potent structural modifier for tailoring phase boundaries and defect chemistry, providing a cost-effective framework for developing high-performance transparent electromechanical materials. Full article

Lagrangian Coherent Structures (LCSs) in the mesoscale circulation of the Western Equatorial Atlantic (WEA), a region governed by the North Brazil Current (NBC) and its retroflection, are analyzed. Observations from 63 surface drifters deployed between 2018 and 2019 were combined with ocean analysis/forecast fields. The Finite-Time Lyapunov Exponent (FTLE) was computed using 15- and 90-day integrations to identify transport barriers and persistent structures. FTLE ridges showed strong seasonal correspondence with drifter trajectories, with 34–74% of drifter positions lying within 0.25° of attracting or repelling LCSs. Characteristic FTLE magnitudes reached ~0.3 d⁻¹, implying particle separation e-folding times of approximately 3.3 days. Spatial agreement between drifter-derived and model-based FTLE fields exhibited similar variability across seasons, with the highest correspondence during periods of intensified frontal activity. These results indicate that a substantial portion of the observed drifter motion follows or remains close to FTLE-defined pathways, supporting the robustness of the Lagrangian structures identified in the WEA. Overall, the study provides the first quantitative LCS-based characterization of mesoscale transport in this region, revealing recurrent eddies, instability zones, and flow boundaries associated with the NBC system and its interaction with the North Equatorial Countercurrent. Full article

Background: Paclitaxel (PTX) is an anti-neoplastic drug that inhibits not only melanoma cell proliferation but also migration and angiogenesis. ICOS-Fc is a recombinant molecule that triggers ICOS ligand (ICOSL) on tumor cells and cells of the tumor microenvironment and inhibits tumor growth, angiogenesis, and metastasis. This study investigated the effects of chitosan nanobubbles loaded with low doses of PTX and surface decorated with ICOS-Fc (ICOS-Fc-NB-PTX) in inhibiting in vitro and in vivo melanoma cell growth and invasiveness. Methods: Preparation and characterization of nanoformulations, as well as in vitro drug release studies, were carried out. Nanoformulations were studied both in vitro and in vivo. In melanoma cells, viability, migration, and invasion assays were analyzed. For the in vivo experiments, C57BL/6 Wild-type (WT) male mice were injected subcutaneously with D4M-3A cells, a murine melanoma cell line engineered to carry the BRAF^V600E mutation. After treatments, in vivo tumor growth, proliferation, and angiogenesis markers were studied. Results: In vitro tests showed the great ability of ICOS-Fc-NB-PTX to inhibit cell viability, migration, and invasion. These results were confirmed in vivo, where the tumors of mice treated with ICOS-Fc-NB-PTX displayed decreased growth accompanied by downregulation of the proliferation marker Ki-67 and reduced development of CD31⁺ blood vessels. Conclusions: In conclusion, the ICOS-Fc-NB-PTX formulation deserves to be further analyzed as a highly effective combination for melanoma, exerting multifaceted anti-tumor activities. Full article

Panulirus ornatus, the ornate spiny lobster, is a stenohaline weak hyper-osmoregulator, yet its osmoregulatory response to salinity stress remains poorly understood. This study investigated six osmoregulatory genes—Na⁺/K⁺-ATPase (nka), V-type H⁺-ATPase (vhe), Na⁺/HCO₃⁻ exchanger (nbc), Na⁺/K⁺/2Cl⁻ co-transporter (nkcc), Na⁺/H⁺ exchanger (nhe), and carbonic anhydrase (ca)—in juvenile gills exposed to 25 ppt, 34 ppt (control), and 40 ppt salinities during acute (48 h) and chronic (>38 d) phases. Transcriptome analysis revealed that all genes were unresponsive following either 25 ppt or 40 ppt salinity acute exposure. However, nkcc showed a tendency toward for upregulation under 25 ppt salinity during acute exposure. Additionally, glutathione S-transferase and putative ferrous reductase 1 were upregulated under 25 ppt salinity, suggesting increased metabolic demand. In contrast, glutathione peroxidase and an ammonia transporter were upregulated in 40 ppt salinity, indicating protein catabolism. Quantitative PCR confirmed nkcc- and nka upregulation under chronic 25 ppt salinity. Vhe, nbc, nhe and ca showed no response, and 40 ppt salinity did not affect the six target genes. These findings suggest P. ornatus relies on nkcc- and nka-mediated ion transport and lacks mechanisms to tolerate high salinity, resulting in reduced growth and survival. These findings define optimal salinity range for aquaculture (25–34 ppt), highlighting the need to avoid high-salinity stress in lobster water quality management Full article

Yellow rust (YR), caused by Puccinia striiformis f. sp. tritici (Pst), is a global disease infecting wheat that seriously affects the yield and the quality of grains. Wheat breeding line C855 is immune to the mixed Pst isolates CYR32 + CYR33 + CYR34 under field conditions. To identify the Yr-loci carried by C855, in this study, an F₂ population derived from the crossing of C855 with Yannong 999, a YR-sensitive cultivar, was established, and the infection type (IT) of each F₂ individual was estimated. The correlation analysis results show that YR resistance was significantly positively correlated with grain weight and grain size. Using a 120K single-nucleotide polymorphism (SNP) array, the F₂ population was genotyped, and a high-density genetic map covering 21 wheat chromosomes and consisting of 5362 SNP markers was built. Then, five Yr-QTLs on chromosomes 1B, 2A, 2B, and 2D were identified. Of these, the QTL on chromosome 2A, temporarily named QYr.sxau-2A.1, is a major-effect QTL explaining 15.62% of the phenotypic variance. One PCR-based marker SSR2A-14 for QYr.sxau-2A.1 was developed, and the C855 allele of SSR2A-14 corresponded to the stronger Yr resistance. QYr.sxau-2A.1, located in the 228.02~241.58 Mbp physical interval, is different from all the known Yr loci on chromosomes 2A. Within the interval, there are 30 annotated genes, including a nucleotide-binding site and a leucine-rich repeat (NBS-LRR)-encoding gene with the linkage marker NRM2A-16 of QYr.sxau-2A.1. Our results reveal a novel major-effect QYr.sxau-2A.1, which provided resistance to YR and is a molecular marker for wheat breeding. Full article

Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims to develop an enhanced way of targeting Trop2 expression in tumors and blocking it using extracellular vesicles (EVs) bioengineered to express a nanobody sequence against Trop2 (NB60 E). Methods: Here, a plasmid construct was designed to express the Trop2 sequence, NB60, flanked with HA tag and myc epitope and a PDGFR transmembrane domain in the C-terminal region, and was transfected into HEK293T cells for EVs isolation. The potency of NB60 E to knock down Trop2 in letrozole-resistant breast cancer cells (LTLT-Ca and MDA-MB-468 cells) was initially investigated. Thereafter, the effects of NB60 E on the cell viability and downstream signaling pathway of Trop2 via MTT assay and Western blotting were determined. Lastly, we also examined whether NB60 E treatment in Jurkat T cells affects IL-6, TNF-α, and IL-2 cytokine production by enzyme-linked immunosorbent assay (ELISA). Results: Results revealed treatment with NB60 E significantly reduced surface Trop2 expression across both cell lines by 23.5 ± 1.5% in MDA-MB-468, and 61.5 ± 1.5% in LTLT-Ca, relative to the HEK293T-derived control EVs (HEK293T E). NB60 E treatment resulted in a marked reduction in LTLT-Ca cell viability by 52.8 ± 0.9% at 48 h post-treatment. This was accompanied by downregulation of key oncogenic signaling molecules: phosphorylated ERK1/2 (p-ERK 1/2) decreased by 30 ± 4%, cyclin D1 by 67 ± 11%, phosphorylated STAT3 (p-STAT3) by 71.8 ± 1.6%, and vimentin by 40.8 ± 1.4%. ELISA analysis revealed significant decreases in IL-6 (−57.5 ± 1.5%, 7.4 ± 0.35 pg/mL) and TNF-α (−32.1 ± 0.3%, 6.1 ± 1.2 pg/mL) levels, coordinated by an increase in IL-2 secretion (22.1 ± 2.7%, 49.2 ± 1.1 pg/mL). Quantitative analysis showed marked reductions in the number of nodes (−45 ± 4.4%), junctions (−55 ± 3.5%), and branch points (−38 ± 1.2%), indicating suppression of angiogenic capacity. In vivo experiment using near-infrared Cy7 imaging demonstrated rapid and tumor-selective accumulation of NB60 E within 4 h post-administration, followed by efficient systemic clearance by 24 h. The in vivo results demonstrate the effectiveness of NB60 E in targeting Trop2-enriched tumors while being efficiently cleared from the system, thus minimizing off-target interactions with normal cells. Lastly, Trop2 expression in LTLT-Ca tumor xenografts revealed a significant reduction of 41.0 ± 4% following NB60 E treatment, confirming efficient targeted delivery. Conclusions: We present a first-in-field NB60 E-grafted EV therapy that precisely homes to Trop2-enriched breast cancers, silences multiple growth-and-invasion pathways, blocks angiogenesis, and rewires cytokine crosstalk, achieving potent antitumor effects with self-clearing, biomimetic carriers. Our results here show promising potential for the use of NB60 E as anti-cancer agents, not only for letrozole-resistant breast cancer but also for other Trop2-expressing cancers. Full article

Rapidly pinpointing the origin of accidental chemical gas releases is essential for effective response. Prior vision pipelines—such as 3D CNNs, CNN–LSTMs, and Transformer-based ViViT models—can improve accuracy but often scale poorly as the temporal window grows or winds meander. We cast recursive backtracking of concentration fields as a finite-horizon, multi-step spatiotemporal sequence modelling problem and introduce Recursive Backtracking with Visual Mamba (RBVM), a Visual Mamba-inspired, directionally gated state-space backbone. Each block applies causal, depthwise sweeps along ${\mathrm{H}}^{\pm }$, ${\mathrm{W}}^{\pm }$, and ${\mathrm{T}}^{\pm }$ and then fuses them via a learned upwind gate; a lightweight MLP follows. Pre-norm LayerNorm and small LayerScale on both branches, together with a layer-indexed, depth-weighted DropPath, yield stable stacking at our chosen depth, while a 3D-Conv stem and head keep the model compact. Computation and parameter growth scale linearly with the sequence extent and the number of directions. Across a synthetic diffusion corpus and a held-out NBC_RAMS field set, RBVM consistently improves Exact and hit $\le 1$ over strong 3D CNN, CNN–LSTM, and ViViT baselines, while using fewer parameters. Finally, we show that, without retraining, a physics-motivated two-peak subtraction on the oldest reconstructed frame enables zero-shot dual-source localization. We believe RBVM provides a compact, linear-time, directionally causal backbone for inverse inference on transported fields—useful not only for gas–release source localization in CBRN response but more broadly for spatiotemporal backtracking tasks in environmental monitoring and urban analytics. Full article

Earthquakes remain among the most destructive natural hazards, causing severe loss of life and property in seismically active regions such as Nepal. Major events such as the 1934 Nepal–Bihar earthquake (M_w 8.2), the 2015 Gorkha earthquake (M_w 7.8), and the 2023 Jajarkot earthquake (M_L 6.4) have repeatedly exposed the vulnerability of Nepal’s built environment. In response, the Ready-to-Use Detailing (RUD) guideline (NBC 205:2024) was introduced to provide standardized structural detailing for low-rise reinforced concrete buildings without masonry infill, particularly for use in areas where access to professional engineering services is limited. This study was motivated by the need to critically assess the structural performance of buildings designed according to such rule-of-thumb detailing, which is widely applied through owner–builder practices. Nonlinear pushover analyses were carried out using finite element modelling for typical configurations on soil types C and D, under peak ground accelerations of 0.25 g, 0.30 g, 0.35 g, and 0.40 g. The response spectrum from NBC 105:2020 was adopted to determine performance points. The analysis focused on global response, capacity curves, storey drift, and hinge formation to evaluate structural resilience. The maximum story drift for the linear static analysis is found to be 0.56% and 0.86% for peak ground acceleration of 0.40 g, for both three and four-storied buildings. Also, from non-linear static analysis, it is found that almost all hinges formed in the beams and columns are in the Immediate Occupancy (IO) level. The findings suggest that the RUD guidelines are capable of providing adequate seismic performance for low-rise reinforced concrete buildings, given that the recommended material quality and construction standards are satisfied. Full article

Background: Biotinidase deficiency (BD) is a common autosomal recessive metabolic disorder in Qatar and the Arab world. It is treatable if detected early, making it essential to understand the genetic variants involved. This study aimed to investigate the carrier frequency of BD-related variants in a healthy Qatari population, reflecting the genetic landscape of the broader Middle Eastern region; classify them using bioinformatics tools; and compare findings with global datasets. Methods: Whole-genome sequencing data from 14,669 participants in the Qatar Genome Program (QGP), a multiethnic cohort including Qatari nationals and long-term residents (≥15 years), were analyzed to identify BTD variants. A total of 723, including 653 single-nucleotide polymorphisms (SNPs) and 70 structural variants (SVs) in BTD associated with BD, were screened against the Qatari cohort and compared with international data. In silico tools were used to assess variant pathogenicity, conservation, and protein stability. Molecular dynamics (MD) simulations were performed to evaluate structural and functional changes in the BTD. Results: A total of 80 SNPs and 3 SVs were identified, among which 21 variants (19 SNPs and 2 SVs) were classified as pathogenic or likely pathogenic, according to ClinVar. The carrier frequency of BTD-related variants in Qatar was 1:20, primarily driven by rs13078881 (D444H). Molecular dynamics (MD) simulations revealed significant conformational changes with H323R, D444H, and P497S, which demonstrated increased flexibility (higher RMSD/RMSF and PCA trace values). Additionally, R209C and D444H showed reduced compactness (higher Rg) and distinct energy minima, suggesting altered conformational states. Conclusions: This study demonstrates a high carrier frequency of pathogenic BTD variants in the Qatari population, underscoring the need to integrate these SNPs and SVs into the national genomic neonatal screening program (gNBS) for enhanced early detection and treatment strategies. The mild structural deviations observed in the D444H mutant through MD simulations may explain its association with milder clinical phenotypes of BTD, offering valuable insights for personalized therapeutic approaches. Full article