Search Results (91)

Background: Bedside manipulation of adult anti-tuberculosis tablets for paediatric dosing is common in low-resource settings, yet it can compromise drug stability. This study investigated how grinding and multi-drug co-suspension affect the supramolecular organisation, thermal stability, and dissolution of isoniazid (INH). Methods: INH raw, INH branded tablets (whole and ground), and multi-drug combination mixtures (MCMs) that simulate paediatric multi-drug-resistant tuberculosis (MDR-TB) regimens were assessed. Samples were analysed as solids and aqueous suspensions using hot-stage microscopy (HSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Raman spectroscopy, FTIR-ATR, USP dissolution, and HPLC (LOD 0.0015 mg mL⁻¹; LOQ 0.005 mg mL⁻¹). Results: Grinding and co-mixing lowered melting points and masked typical INH events. Spectroscopy revealed the broadening and shifting of OH/NH and pyridine-ring bands, consistent with the formation of new hydrogen-bonding networks, correlative with supramolecular rearrangements. In multi-drug suspensions, INH fell below the HPLC quantification limit in both pH 1.2 and 6.8 media, despite visible residue, suggesting the formation of non-dissociable supramolecular complexes. Using a validated HPLC assay, no quantifiable INH was detected from the crushed multi-drug suspensions in either pH 1.2 or pH 6.8, whereas intact API/tablets showed measurable release. Conclusions: Co-suspension of INH with companion tuberculosis (TB) drugs disrupts its supramolecular integrity, leading to pre-administration degradation and a loss of quantifiable drug. Dissolution testing showed minimal INH release at pH 1.2 and none at pH 6.8, contrasting with intact tablets/API. These observations highlight that converting an immediate-release tablet into an aqueous suspension fundamentally alters its physicochemical environment and requires rational formulation design to preserve molecular stability, differentiating true resistance from formulation failure. Full article

Hybrid railway assets such as workshops and depots combine building, mechanical, electrical and plumbing (MEP)/industrial, and linear infrastructure domains, increasing coordination complexity and challenging continuity from the Project Information Model (PIM) to the Asset Information Model (AIM). Although Employer’s Information Requirements (EIR), Asset Information Requirements (AIR), and the BIM Execution Plan (BEP) prescribe deliverables and processes, a persistent gap remains between documentary prescriptions and the auditable evidence needed to support traceable decisions within the Common Data Environment (CDE). This paper proposes an ISO 19650-aligned governance framework that operationalizes the EIR/AIR → BEP → CDE transition by: (i) structuring the asset using Functional Units (FUs) as a stable anchor for PIM → AIM continuity; and (ii) implementing a pre-Published Quality Gate that separates control into three non-substitutable dimensions (spatial, semantic, and data). The approach is implemented as a tool-neutral, reproducible workflow (inputs → checks → outputs → publish) and produces a minimal, persistent evidence package in the CDE (file-level report, package summary, publish/hold decision record, and Nonconformity Report (NCR)/BIM Collaboration Format (BCF) traceability), with explicit roles governing the Shared → Published transition. Across 22 Industry Foundation Classes (IFC), deliverables from two depot cases and multiple delivery states, All Gates Pass ranged from 25.0% to 44.4% depending on Case × State; overall, 14/22 deliverables (63.6%) would be held pending correction under the gate. Although validated on Spanish railway depots, the framework is grounded in ISO/openBIM standards and is designed for transferability to other international contexts and complex asset types where multidisciplinary federation and PIM → AIM continuity pose similar challenges. Full article

Targeted therapies and chemoimmunotherapy have transformed outcomes for non–small cell lung cancer (NSCLC), yet relapse remains common. Resistance is increasingly recognized to include an early, largely reversible phase in which a minor subpopulation survives lethal therapy through non-genetic adaptation. These drug-tolerant persister (DTP) cells may be quiescent or cycling, and provide a reservoir from which stable, genetically resistant clones can later emerge. In parallel, late recurrence may reflect tumor dormancy, in which disseminated or residual cells persist for prolonged periods under microenvironmental constraint and/or immune surveillance. This review integrates DTP and dormancy frameworks in NSCLC, summarizes mechanisms that sustain persistence (chromatin and transcriptional plasticity, stress signaling, metabolic rewiring, and stromal/immune protection), and highlights experimental models and translational readouts, including circulating tumor DNA (ctDNA)–based minimal residual disease (MRD) monitoring. We also discuss potential therapeutic concepts to prevent DTP formation, exploit persister liabilities, or enforce dormancy in minimal-disease settings. A mechanistically grounded understanding of these survival programs is essential for rational combinations and biomarker-guided trials aimed at durable remission. Full article

Benchmarking Spanish reading comprehension remains challenging due to the scarcity of proficiency-calibrated resources grounded in authentic human assessments. We introduce IC-UNED-RC-ES, a benchmark comprising more than 6000 items derived from Instituto Cervantes examinations, converted to a machine-readable format while preserving exam structure, proficiency levels, and scoring criteria. Unlike many existing resources, IC-UNED-RC-ES includes a diverse set of exercise formats, combining common multiple-choice questions with new formats such as matching and fill-in-the-gap, which support a broader assessment of reading skills. The benchmark supports evaluation at both the item and exam levels and includes an exercise taxonomy with category-specific metrics. Baseline results with current AI systems reveal a strong difficulty effect (a 15-point drop from lower to advanced levels) and substantial variation across exercise types, with inference- and discourse-heavy categories reaching only 41%. IC-UNED-RC-ES provides a human-aligned, interpretable testbed for diagnosing strengths and weaknesses in Spanish reading comprehension and for tracking progress across model generations. Full article

Background: International policy increasingly recognises the importance of inclusive, community-based support for people living with dementia. Football, as a culturally significant sport, has the potential to reach older adults and communities disproportionately affected by health inequalities. The objectives of this review were to collate evidence on football-based dementia initiatives, including intervention format, delivery approaches, and reported outcomes. Methods: Seven databases (Sportdiscus, MEDLINE, Embase, Scopus, PsycINFO, CINAHL, and Web of Science) were searched for relevant peer-reviewed and grey literature from their inception to June 2025. The PICO framework was used to define eligibility criteria. Eligible studies described community-based football-themed or football-based programmes involving people living with dementia. Data were extracted on participant sample, intervention characteristics, and reported outcomes, and iteratively charted. Results: In total, 11 of the 1059 identified articles were included within this review. Initiatives were often delivered through professional football clubs and charitable foundations, with formats ranging from reminiscence therapy sessions to walking football. Common outcomes for participants included increased sociability, improved mood, enhanced communication, and a strengthened sense of identity and belonging. Some interventions also reported physical benefits, such as improved mobility. Carers highlighted respite opportunities, peer support, and enjoyment from seeing relatives more engaged. Despite positive reports, outcome measurement was inconsistent, and most studies were small-scale or descriptive pilot projects. Conclusions: Football-based dementia initiatives provide meaningful, culturally grounded opportunities for social inclusion and support. Their delivery through community clubs/organisations positions them well to address inequities in dementia care, particularly in areas of disadvantage. However, stronger evaluation methods are required to build a robust evidence base and guide sustainable implementation at scale. Full article

The analysis of ground-penetrating radar data generally relies on the visual identification of structures on selected profiles and their interpretation in terms of buried features. In simple cases, inverse modelling of the acquired data set can facilitate interpretation and reduce subjectivity. These methods suffer from severe restrictions due to antenna resolution limits, which prevent the identification of tiny structures, particularly in forensic, stratigraphic, and engineering applications. Here, we describe a technique to obtain a high-resolution characterization of the underground, based on the forward modelling of individual traces (A-scans) of selected radar profiles. The model traces are built by superposition of Ricker wavelets with different polarities, amplitudes, and arrival times and are used to create reflectivity diagrams that plot reflection amplitudes and polarities versus depth. A thin bed is defined as a layer of higher or lower permittivity relative to the surrounding material, such that the top and bottom reflections are subject to constructive interference, determining the formation of an anomalous peak in the trace (tuning effect). The proposed method allows the detection of ultra-thin layers, well beyond the Rayleigh vertical resolution of GPR antennas. This approach requires a preliminary estimation of the instrumental uncertainty of common monostatic antennas and takes into account the frequency-dependent attenuation, which causes a spectral shift of the dominant frequency acquired by the receiver antenna. Such a quantitative approach to analyzing radar data can be used in several applications, notably in stratigraphic, forensic, paleontological, civil engineering, heritage protection, and soil stratigraphy applications. Full article

Design studios remain a core component of architectural education, yet their pedagogical structure, alignment with international standards, and contribution to professional formation are often insufficiently examined. This study evaluates master-level design studios using a three-track analytical framework that integrates pedagogical innovation, alignment with the UNESCO-UIA Charter for Architectural Education, and the development of professional capabilities specified in the UNESCO-UIA Validation System. The methodology combines qualitative profiling and quantitative benchmarking, employing a structured six-parameter innovation framework, an ordinal evidence scale, and a cross-track correlation analysis. Learning and professional capabilities were assessed and analyzed through Pearson correlation matrices in JASP (0.95.4). Findings reveal that all studios share a common grounding in heritage- and environment-responsive learning, yet demonstrate distinctive pedagogical signatures shaped by thematic focus, design scale, and temporal orientation. Strong positive alignments emerge between context-driven learning and applied professional readiness, while structural gaps indicate capability areas insufficiently supported by studio pedagogies. The study demonstrates that bridging policy frameworks with pedagogical and professional capability assessments provides a replicable method for evaluating architectural curricula, offering insights for improving design-studio models and strengthening evidence-based educational practice. Full article

Vampire bats likely first appeared in South America in the early Miocene (~20 Ma) and evolved to feed upon the blood of native South American mammals of medium to large body size, in particular, xenarthrans–ground sloths, armadillos, pampatheres, and glyptodonts, and native ungulates–notoungulates and litopterns. Following the formation of the Panamanian Isthmus (~5 Ma), vampire bats immigrated into North America as participants in the Great American Biotic Interchange, following their preferred prey species, probably xenarthrans. The earliest records of vampire bats are the extinct species Desmodus archaeodaptes from three early Pleistocene faunas in Florida. The large extinct vampire D. stocki occurs in 18 late Pleistocene faunas in the southern US and Mexico. The giant extinct vampire D. draculae is known from eight late Pleistocene faunas from Mexico and Belize south to Brazil and Argentina. The late Pleistocene extinction of D. draculae and D. stocki coincided with the extinction of their primary source of blood, the mammalian megafauna. The common vampire bat D. rotundus survived and now occurs throughout tropical America because it had a broader prey base, feeding on the blood of a variety of medium- to large-sized mammals, and currently preying preferentially on non-native domestic livestock. Full article

A detailed investigation of the structure–property relationships of three-antennary oligoglycines in aqueous solutions is performed. Two representatives of these substances are investigated: CH₃C(-CH₂-NH-Gly₅)₃ and CH₃C(-CH₂-NH-Gly₇)₃. The aim is to clarify the effect of molecular peculiarities and the concentration of the oligoglycines on bulk-solution performance and on adsorption-layer properties at the solution–air interface. This study is focused on the clarification of the conditions for the onset of bulk and interfacial supramolecular species in the aqueous environment. The presence of oligoglycine antennae attached to a common carbon-atom center allows the formation of highly coordinated intra- and intermolecular ‘click-clack’ interactions and presumes the possibility for the development of extended H-bonded networks, e.g., in the form of Polyglycine II motifs. A combined study protocol, including dynamic light scattering, profile analysis tensiometry, and microscopic thin-liquid-film techniques, is applied. The results allow the drawing of essential conclusions about the possible coupling mechanism of bulk and interfacial phenomena. The outcomes give grounds to advance the following hypothesis: due to the synchronized action of noncovalent interactions, three types of tectomeric structures may appear—dimers, gel-like elements, and disk-like supramolecular entities. Options for fine-tuning of the tectomer formation in aqueous solutions are presented, and possible application routes are outlined. Full article

Concrete structures develop several defects as the structure ages. One of the common concerns in structural integrity is the formation of cracks, which demands regular inspection with precision. In this study, a bridge underpass arch structure was inspected with the help of an Unmanned Aerial Vehicle (UAV) in a coastal region of the Mediterranean Sea, where 2D captured images were transferred into a 3D model for better visualisation from a Structural Health Monitoring (SHM) perspective. The images with cracks were manually annotated, using the VGG tool, by an expert. Using the 3DF Zephyr software, from sparse to dense point clouds, and 3D mesh to orthophoto, all 3D models were constructed from the annotated and unannotated images of the structure. The 3D model achieved a Ground Sampling Distance of 0.0046 m/pixel, with an image alignment of 60%. The Bundle Adjustment Mean Reprojection Error confirmed satisfactory internal model accuracy. The final assessment through the orthophoto, where a resolution of 4531 × 2433 pixels was achieved, revealed that the images were of sufficient quality to capture the details and the defects present, and better visualisation could be made. This output demonstrates that UAV-based photogrammetry is time- and cost-efficient and surpasses the traditional visual inspection of confined structures. Full article

This study presents the development and validation of an in situ monitoring method for the laser direct energy deposition (DED) process, utilizing an integrated optical camera (720 HD, 60 fps) to analyze melt pool imagery. The approach is grounded in an experimental framework employing Taguchi orthogonal arrays, which ensures a stable dataset by controlling process variability and enabling reliable extraction of relevant features. The monitoring system focuses on analyzing brightness distribution regions within the melt pool image, identified as specific clusters that reflect external process conditions. The method emphasizes precise segmentation of the melt pool area, combined with automatic detection and classification of cluster features associated with key process parameters—such as focus distance, the number of deposited layers, powder feed rate, and scanning speed. The main contribution of this work is demonstrating the effectiveness of using an optical camera for DED monitoring, based on an algorithm that processes a set of melt pool identification features through computer vision and machine learning techniques, including Random Forest and HistGradient Boosting, achieving classification accuracies exceeding 95%. By continuously tracking the evolution of these features within a closed-loop control system, the process can be maintained in a stable, defect-free state, effectively preventing the formation of common process defects. Full article

The structural performance of mid-rise buildings with a soft first story is a critical issue in earthquake-prone regions. This paper presents a detailed assessment of both the seismic performance and the structural reliability of a confined masonry mid-rise building with a soft reinforced-concrete first-story irregularity located in Mexico. This structure was designed according to outdated building codes to reflect construction practices that remain common in some parts of the country. Nonlinear dynamic analyses were conducted using ETABS v21. To simulate various seismic scenarios, ground motion records associated with return periods of 72, 475, and 975 years, respectively, were implemented. The results demonstrated that maximum inter-story drift is predominantly concentrated at the first story, exceeding the performance thresholds for immediate occupancy, life safety, and collapse prevention. Furthermore, a probabilistic performance assessment was developed considering the randomness of inter-story drift responses. Then, reliability index (β) was calculated for each seismic scenario. In all cases, β values remained consistently below the minimum recommended limit. These findings confirm the formation of a soft-story mechanism at the first level and are relevant for buildings designed under construction provisions like those used in the present case study. Full article

As architectural educators interested in community engagement and learning about everyday practices in the city, we recognize that teaching community engagement in a practical rather than abstract way is key. This paper presents community-engaged architecture and design pedagogy as potential methods for informing the shift in the role of the architect from top-down to ground-up. This paper presents the author’s pedagogical experimentation based on 25 years of teaching live projects in socially engaged architecture and activism. It describes how a pedagogy combining architecture and activism resulted in the development of an interdisciplinary commons curriculum. The curricula aimed to increase the influence of design practitioners in the development of deliberatively democratic neighborhoods by creating new design practices and outputs. Teaching the political role of the architect from the ground-up rather than from the traditional top-down perspective is challenging, as only a few historical case studies can legitimize and inform its development. This paper describes the content of two pedagogical formats. The ‘Architecture and Activism’ postgraduate architecture and design studio and the following ‘Design for Cultural Commons’ interdisciplinary design postgraduate program. They were both designed to have real-world influence. The ‘Design for Cultural Commons’ postgraduate program enabled the development of a curriculum ranging from modules in social science, art and politics to systems thinking, which is required knowledge for complex neighborhood practices. The city was used as a field of study to discover new knowledge through students’ community engagements. Various theoretical frameworks were employed to develop new forms of emancipatory pedagogy, helping the author unlearn the norms of conventional architectural education. The practice of recalibrating architectural canons and values into a common-based curriculum development is discussed through the framing of learning commons. Full article

Collagen is a family of large, fibrous biomacromolecules common in animals, distinguished by unique molecular, structural, and functional properties. Despite the relatively low complexity of their sequences and the repetitive conformation of the triple helix, which is the defining feature of this family, unraveling sequence–stability and structure–function relationships in this group of proteins remains a challenging task. Considering the importance of the structural aspects in collagen chain recognition and selection, we reviewed our current knowledge of the heterotrimeric structures of non-collagenous (NC) regions that lack the triple helix sequence motif, Gly-X-Y, and are crucial for the correct folding of the functional states of these proteins. This study was conducted by simultaneously surveying the current literature, mining the structural database, and making predictions of the three-dimensional structure of these domains using highly reliable approaches based on machine learning techniques, such as AlphaFold. The combination of experimental structural data and predictive analyses offers some interesting clues about the structural features of heterotrimers formed by collagen NC regions. Structural studies carried out in the last decade show that for fibrillar collagens (types I, V, XI, and mixed V/XI), key factors include the formation of specific disulfide bridges and electrostatic interaction patterns. In the subgroup of collagens whose heterotrimers create supramolecular networks (types IV and VIII), available structural information provides a solid ground for the definition of the basis of the molecular and supramolecular organization. Very recent AlphaFold predictions and structural analyses of type VI collagen offer strong evidence of the specific domains in the NC region of the protein that are involved in chain selection and their staggering. Insightful crystallographic studies have also revealed some fundamental elements of the chain selection process in type IX collagen. Collectively, the data reported here indicate that, although some aspects (particularly the quantification of the relative contribution of the NC and triple helix regions to correct collagen folding) are yet to be fully understood, the available structural information provides a solid foundation for future studies aimed at precisely defining sequence–structure–function relationships in collagens. Full article

As urban-living heritage sites, mountainous historic districts face the dual challenges of authenticity preservation and living development and the diverse and complex needs of different user groups. To address these challenges, this study systematically examines the cognitive differences between residents and merchants in mountainous historic districts and their implications for sustainable heritage management, using the Ciqikou Historic District in Chongqing as a case study. Through grounded theory methodology, we investigate residents and merchants via questionnaires and semi-structured interviews. Using coding analysis, the study reveals the cognitive similarities and differences of different users toward mountainous historic districts and explores their formation mechanisms, focusing on the spatial differentiation of cognition influenced by topographical and locational factors. Results indicate that both user groups share common cognitive concerns regarding building safety, transportation, policies, and infrastructure. Residents prioritise aspects related to daily convenience, whereas merchants focus more on economic benefits, leading to differences in their cognitive classifications and evaluations. Location plays a significant role in shaping user cognition, with notable cognitive differences observed between residents and merchants across different locations, and intra-group variation exists within the same user group at different locations. Based on a living–authenticity theoretical framework, this study constructs a living development–authentic preservation strategic framework and a multidimensional synergistic implementation framework encompassing integrity–locality–user, providing effective pathways for the preservation and sustainable development of mountainous historic districts. Full article