Search Results (10,783)

The compound 3-((benzyloxy)carbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid was successfully synthesized. High-quality crystals were obtained, and its X-ray structure was solved and refined by Hirshfeld atom refinement using custom aspherical scattering factors with the Olex2/NoSphereA2 package. Hydrogen bonding interactions lead to head-to-head carboxylic acid dimer formation. A positional disorder for the bridging H-atom was detected and modeled to two parts in a 0.85:0.15 ratio. Detailed comparison with a neutron diffraction study of benzoic acid at the same temperature (100 K) demonstrates that the E–H-bond distances in the title compound are in excellent agreement (differing less than 1%) and the displacement ellipsoids volumes to the model are also in excellent agreement to the neutron diffraction structure. Moreover, both the variation in refined disorder occupancy and differences in C=O and C–O lengths of the disordered carboxylic acids in the two structures track well with their dimer O···O separations. This is longer by 0.023 Å in the structure of the title compound than in that of benzoic acid. A database search was conducted and used for comparison of the title compound to other high-quality structures of bicyclo[1.1.1]pentane-containing species. Full article

The role of petting zoo animals in the dissemination of disease has been widely studied, yet understanding the potential reservoir of antimicrobial resistance (AMR) in these centres has not been explored in the United Kingdom (UK). To understand the carriage of AMR pathogens within petting zoos, this study aimed to identify AMR in E. coli and Staphylococcus intermedius group (SIG) isolated from faeces and skin, respectively, including selective cultures for ESBL-E. coli and methicillin-resistant staphylococci. Faecal samples and skin swabs were collected from 166 petted mammals across eight UK centres to recover E. coli and coagulase-positive staphylococci (CoPS), respectively, through enrichment culture methods, plating onto non-selective (tryptone bile-x agar, mannitol salt agar) and selective media (ESBL ChromID, mannitol salt agar with 6 mg/L oxacillin). Antimicrobial susceptibility was assessed using Kirby-Bauer disc diffusion, covering eight classes of antimicrobials. Antimicrobial usage records from the past 12-months were obtained from 7/8 centres. Overall, 145/166 faecal samples yielded 223 E. coli isolates, with an overall AMR prevalence of 42.6%. Thirteen E. coli isolates (from 8.5% of animals) were classified as multidrug-resistant. ESBL-producing E. coli were detected in 5/166 faecal samples. From 166 skin swabs, 84 yielded CoPS isolates, with S. aureus (n = 70), SIG (n = 13) and S. hyicus (n = 1) identified. Overall, 25.3% of SIG isolates exhibited resistance to at least one antimicrobial. Antimicrobial usage correlated positively with AMR prevalence for E. coli (p < 0.001), though was not associated with multidrug-resistance. This study demonstrates for the first time the presence of AMR within bacteria isolated from UK petting zoo animals, highlighting this reservoir of AMR bacteria. Full article

Nitrosamines (NAs) pose a risk due to their carcinogenic properties, especially in processed and cured meats where nitrites and nitrates are widely used. The objective of this study was to develop an integrated Ultra-High-Performance Liquid Chromatography–High-Resolution Mass Spectrometry (UHPLC–HRMS) workflow for detecting both volatile (VNAs) and non-volatile (NVNAs) nitrosamines in meat matrices. Comparison of two ionization techniques showed that heated electrospray ionization (HESI) and atmospheric pressure chemical ionization (APCI) provided complementary coverage and sensitivity. Extraction and cleanup were optimized for meat, although recovery rates remained variable, underscoring the analytical complexity. The method was applied to raw, cooked, cured, and grilled meats, as well as to in vitro gastric digestion and co-digestion with spinach. Results revealed that some NAs were present even in untreated raw meat (≈3.0 µg/kg, N-nitrosodi-n-butylamine), while the addition of nitrites and nitrates significantly increased their levels (more than 10 µg/kg, N-nitrosodiethylamine, N-nitrosodimethylamine, N-nitrosodi-n-butylamine). Gastric digestion was the most critical condition, further promoting nitrosamine formation, particularly for N-nitrosodiethylamine, N-nitrosodi-n-butylamine, and N-nitrosopiperidine. Ascorbate exhibited a dual role, acting as an inhibitor at low nitrite concentrations but becoming pro-oxidant at high levels (300 mg/kg). Cooking alone had limited impact, whereas cooking combined with digestion yielded the highest and most consistent nitrosamine concentrations. The inclusion of spinach during digestion modestly altered nitrosamine levels, reflecting both its nitrate content and polyphenolic profile. Nonparametric ANOVA (aligned rank transform) confirmed that preservative treatment, rather than processing or interaction effects, was the main driver of variability (total nitrosamines: H = 24.15, p = 2.33 × 10⁻⁵), with the combination of preservative ascorbate plus nitrite producing significantly higher levels than other treatments (q = 0.000656). N-nitrosodimethylamine consistently emerged as the most relevant marker for dietary exposure, in agreement with EFSA guidance. Overall, this study underscores both the analytical and biochemical complexity of nitrosamine detection and formation in meat products, while highlighting the importance of preservative formulation and the potential role of dietary antioxidants in mitigating exposure. Full article

Studies of the genetic diversity of ‘Candidatus Liberibacter asiaticus’ strains based on housekeeping genes have been unsuccessful. The increasing availability of complete genome sequences of several strains from different countries has allowed the identification of regions having greater variability, which have been successfully implemented for the bacterium characterization, including microsatellites, genes of prophage origin, and miniature transposable elements with inverted-repeats (MITEs). In the present work, the genetic structure of 147 ‘Ca. L. asiaticus’ strains from nine provinces of Cuba were investigated using two polymorphic regions, consisting of typing for prophages and MITEs. The results showed an important level of coexistence of type 1 and 2 prophages in the Cuban strains, while the type 3 prophage was not detected. Likewise, a high rate of co-occurrence of both types of MITEs (MCLas-A and -B) was also observed. However, the MITE MCLas-A was detected only in its empty form. The double-locus analysis allowed the identification of eight genotypes. Out of these, seven genotypes were present in the Western region, which constitutes the region with the highest genetic variability. This is the first report of a genetic characterization of Cuban strains of ‘Ca. L. asiaticus’ with polymorphic markers in orchards growing in commercial citrus regions. Full article

Background: Cryptosporidium spp. cause opportunistic infections in immunosuppressed individuals, such as people living with HIV (PLWH). However, the association between giardiasis and HIV infection remains uncertain. This study assessed co-infections in Ghanaian PLWH and HIV-negative individuals, analyzing socio-economic, clinical, and immunological implications, including the Giardia duodenalis assemblage and Cryptosporidium spp. sub-family levels. Methods: Stool samples from Ghanaian PLWH were tested using several real-time PCR assays targeting G. duodenalis at the species level and assemblages A and B to optimize diagnostic accuracy. GD60 gene-based Sanger sequencing was used for Cryptosporidium spp. subtyping. Results were correlated with anonymized patient data to evaluate interactions with HIV infection. Results: In PLWH, C. hominis Ib, C. hominis Ie, and C. parvum IIc were detected at similar frequencies, followed by C. hominis Ia, C. hominis Id, and C. parvum IIe in decreasing order. Only C. parvum IIc was repeatedly observed in individuals with CD4+ T cell counts above 200/µL, while other sub-families occurred preferentially in those with lower counts. C. hominis Ia and Ib were associated with PLWH not receiving antiretroviral therapy; C. hominis Ia was linked to recently diagnosed HIV infections. No relevant associations between G. duodenalis assemblages and HIV infection were found. Conclusions: Sub-families Ia and Ib of C. hominis preferentially occur in individuals with severe immunosuppression, while C. parvum IIc is also detectable in individuals with better immune function. The prevalence of giardiasis in Ghana appears to be influenced by factors other than HIV-induced immunosuppression. Full article

STEM (Science, Technology, Engineering, and Mathematics) education faces the challenge of incorporating advanced technologies that foster motivation, collaboration, and hands-on learning. This study proposes a portable system capable of transforming ordinary surfaces into interactive learning spaces through gamification and spatial perception. A prototype based on multi-agent architecture was developed on the PANGEA (Platform for automatic coNstruction of orGanizations of intElligent agents) platform, integrating LIDAR (Light Detection and Ranging) sensors for gesture detection, an ultra-short-throw projector for visual interaction and a web platform to manage educational content, organize activities and evaluate student performance. The data from the sensors is processed in real time using ROS (Robot Operating System), generating precise virtual interactions on the projected surface, while the web allows you to configure physical and pedagogical parameters. Preliminary tests show that the system accurately detects gestures, translates them into digital interactions, and maintains low latency in different classroom environments, demonstrating robustness, modularity, and portability. The results suggest that the combination of multi-agent architectures, LIDAR sensors, and gamified platforms offers an effective approach to promote active learning in STEM, facilitate the adoption of advanced technologies in diverse educational settings, and improve student engagement and experience. Full article

Digital Mobility outcomes can serve as objective biomarkers of health, but their validation in populations with multiple long-term conditions (MLTCs) based on wrist-worn devices remains unexplored. We refined, improved, and introduced novel algorithms, specifically tailored and adapted for (i) gait sequence detection, (ii) initial contact identification, and (iii) stride length estimation from a single wrist-worn device. Validation was performed using data from 28 participants with co-occurring MLTCs performing a 2.5 h real-world monitoring session. Reference data from an established multi-sensor system were used to assess algorithm performance across diverse gait patterns of co-occurring MLTCs. Twenty-eight participants (mean age 70.4 years, 43% females) had a median of three co-occurring MLTCs. Among six gait sequence detection methods, improved versions of the Kheirkhahan algorithm performed best (accuracy = 0.92, specificity = 0.96). For initial contact detection (nine methods tested), Shin’s algorithm achieved the highest performance index (0.85) followed by McCamley (0.84). Stride length estimation was most accurate using novel approaches based on the Weinberg method (performance index > 0.70). The proposed fine-tuned algorithms, the newly developed adaptive variants, and the foot-length augmented versions demonstrated robust performance, surpassing many existing methods and addressing the complexity of gait patterns in MLTCs. These findings enable scalable, real-time mobility monitoring in complex clinical populations using accessible wearable technology. Full article

Electrogenerated chemiluminescence (ECL) is a powerful analytical technique that combines the best features of both electrochemical and photoluminescence methods. In this work, we present a direct ECL-based method for the detection of fentanyl using unmodified screen-printed electrodes. The analysed system consists of tris(2,2′-bipyridyl)ruthenium(II) (Ru(bpy)₃²⁺) as the luminophore and fentanyl as the co-reactant. A comprehensive optimization of the experimental parameters, such as buffer pH, luminophore concentration and working electrode material, was performed in order to maximize the ECL response. The optimal conditions are identified as PBS buffer pH 6, 2.5 × 10⁻³ M Ru(bpy)₃²⁺ and bare gold screen-printed electrodes. Under these conditions, the system exhibited a strong and reproducible ECL signal, with a linear response to fentanyl concentration from 1 × 10⁻⁷ to 1 × 10⁻⁵ M and a limit of detection of 6.7 × 10⁻⁸ M. Notably, the proposed method does not require electrode surface modification, sample pretreatment or complex instrumentation, offering a rapid, sensitive, and cost-effective alternative for fentanyl detection. Furthermore, the storage of bare SPEs at room temperature in a dry place ensures their stability over months or even years, overcoming the limitations offered by ECL systems based on modifications of the working electrode with different nanomaterials. These findings highlight the potential of the proposed ECL approach as a robust and sensitive tool for the detection of synthetic opioids. Its simplicity, portability, and analytical performance make it particularly attractive for forensic and clinical applications where rapid and accurate opioid screening is essential. Full article

The presence of impurities such as Ca, Mg, and Al during the precipitation of rare earths (REs) using ammonium bicarbonate directly affects product purity. It is necessary to optimize precipitation methods and conditions to improve the separation efficiency between REs and impurities. In this study, RE (La and Ce) ions were precipitated using ammonium bicarbonate solution, and the separation efficiency of REs from Al, Fe, Ca, and Mg ions was investigated with or without the addition of triammonium citrate (TAC). The results showed that as long as the precipitation yield of REs was controlled below 94%, Ca and Mg ions would not enter the precipitation in the absence of other impurities, and the purity of the obtained rare earth oxides (RE₂O₃) was close to 100%. The presence of Al and Fe impurities would reduce the separation efficiency of REs from Ca and Mg. Therefore, Al and Fe must be separated before the precipitation of REs. First, Fe was completely precipitated by controlling the pH value to 4.12. Then, by filtering out the isolation and adjusting the pH value to 4.6, approximately 84% of Al³⁺ was precipitated, with a loss of REs of about 6%. Finally, the pH value was increased to 6.43, and REs were completely precipitated, yielding rare earth carbonate. The RE₂O₃ purity of its calcination product was 97.8% with Al and Mg contents of 1.05% and 0.21%, respectively, and no Ca or Fe was detected. This indicated that Mg can enter the product by co-precipitation with Al. To address this, a small amount of TAC was added during the pre-removal of Fe and Al to facilitate the complete removal of Al. By controlling the precipitation yield of REs at 94%, the purity of the final RE₂O₃ reached 99.6% with an Al content of 0.09%. Furthermore, using a continuous precipitation crystallization method, RE₂O₃ purity can be achieved at 99.8% with an Al content of 0.06%. Full article

Background/Objectives: Antimicrobial resistance is a critical global health challenge. Among resistant pathogens, the group of bacteria collectively referred to as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) is of particular concern due to their ability to evade multiple classes of antimicrobials. This study aimed to investigate the occurrence and resistance patterns of ESKAPE bacteria in wild birds from Northern and Central Italy sites, and to assess the presence of other bacteria of public health relevance. Methods: Cloacal swabs were collected from 141 wild birds. Samples were processed on selective and differential media, and bacterial identification was performed using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Antimicrobial susceptibility was evaluated through Minimum Inhibitory Concentration assays and interpreted according to international guidelines. Results: Thirty-seven isolates belonging to the ESKAPE group were identified: E. faecium (n = 10), K. pneumoniae (n = 9), P. aeruginosa (n = 8), Enterobacter spp. (n = 7), S. aureus (n = 2), and A. baumannii (n = 1). Multidrug-resistant isolates were observed among K. pneumoniae and Enterobacter hormaechei. Escherichia coli, although not included in the ESKAPE group, was frequently detected and often co-isolated with clinically relevant bacteria, highlighting its potential role as a reservoir of resistance genes. Conclusions: Wild birds can harbor resistant bacteria of clinical importance, including multidrug-resistant ESKAPE species. Their presence in avian populations underscores the role of wildlife in the environmental dissemination of antimicrobial resistance, with implications for both animal and human health. Full article

Detecting deception in emotionally grounded natural language remains a significant challenge due to the subtlety and context dependence of deceptive intent. In this work, we use a structured behavioral dataset in which participants produce truthful and deceptive statements under emotional and social constraints. To maintain label accuracy and semantic consistency, we propose a multilayer validation pipeline combining selfconsistency prompting with feedback-guided revision, implemented through the CoTAM (Chain-of-Thought Assisted Modification) method. Our results demonstrate that this framework enhances deception detection by leveraging a sentence decomposition strategy that highlights subtle emotional and strategic cues, improving interpretability for both models and human annotators. Full article

Background and Objectives: TAM receptors—Tyro3, Axl, and Mer—and their ligand Growth Arrest-Specific 6 (Gas6) represent a pleiotropic system implicated in fibrosis. Increased Gas6 and Axl expression have previously been observed in lung samples and fibroblast cultures from Idiopathic Pulmonary Fibrosis (IPF) patients. The study explored the contribution of Gas6/TAM system in fibrosis development and the impact of its pharmacological inhibition in fibroblasts. Materials and Methods: IPF fibroblasts (IPF FBs) and control human pulmonary fibroblasts (HPFs) were treated with R428 (Axl-specific inhibitor), LDC1267 (TAM inhibitor), or Nintedanib (an IPF-approved drug) to evaluate the influence of these drugs on cell proliferation, migration, and the expression of pro-inflammatory and pro-fibrotic genes. Fibroblast-to-myofibroblast differentiation was induced by TGF-β. The impact of IPF FBs and HPF on macrophage polarization was investigated through a co-culture of fibroblasts with monocyte-derived macrophages, with the further gene expression analysis of markers of the M1 (pro-inflammatory) or M2 (pro-fibrotic) polarization forms. Results: Cell proliferation was monitored in fibroblasts treated with TGF-β, the drugs, and their combination. In the presence of LDC1267 and Nintedanib, minor differences in cell confluence were detected between IPF FBs and HPFs; R428 (1 μM) seemed to have a higher inhibitory impact on IPF FBs. Regarding cell migration, the fibroblasts treated with LDC1267 exhibited slower wound closure. R428 treatment led to a relative wound closure of 76% in HPFs but only 56% in IPF FBs (60 h). R428 (1 μM) significantly reduced the expression of the pro-fibrotic markers ACTA2, COL1A1, and FN1 in HPFs and IPF FBs compared to TGF-β treatment. HPFs and IPF FBs co-cultured with monocyte-derived macrophages demonstrated a significantly increased expression of MRC1 while the expression of FN1, TNFα, and CXCL10 was moderately increased. Conclusions: These findings suggest that R428 and LDC1267 modulate the proliferation, migration, and gene expression of activated fibroblasts via TAM signaling. Fibroblast-mediated effects on macrophage polarization underscore the relevance of intercellular crosstalk in fibrotic disease. Full article

This study introduces an innovative microfluidic-based approach for extracting drugs from oral fluids using self-assembled tripeptide hydrogels as sorbents. Peptide microfiber derived from the heterochiral tripeptide ^DLeu-^LPhe-^LPhe was formed in situ within the 14 mm-long microchannel of a two-inlet microfluidic device. The methodology enables the laminar flow-driven mixing of buffer solutions, inducing hydrogel formation at their interface. The resulting fiber exhibited a well-defined morphology and β-sheet structure, confirmed by Raman spectroscopy and Thioflavin T fluorescence. The peptide fibers co-assembled successfully with 5-fluorouracil (5-FU) and naproxen (39.8 ± 1.4 nmol of 5-FU and 27.4 ± 6.6 nmol of naproxen per 112 nmol of peptide used to prepare the fiber), resulting in a molar ratio drug/peptide ratio of approximately 1:3 and 1:4, respectively, demonstrating versatility in drug entrapment. The use of the gel fiber as a sorbent phase was first assessed in buffer, and subsequently, the optimized method was applied to saliva. Adsorption studies under stopped-flow conditions showed a significant drug adsorption capability from buffered solutions by the pre-formed hydrogel (32.8 ± 0.9% of 5-FU and 36.4 ± 3.3% of naproxen per fiber preformed with 112 nmol of peptide), demonstrating their suitability as sorbent material. The extension of the methodology to simulated saliva samples allowed extraction of 36% of 5-FU by the fiber, as determined by ¹⁹F NMR spectroscopy on microcoils, which enabled us to work with the small volume of fluid extracted from the microfluidic device and provided clean spectra and quantitative results. These findings highlight the potential of this tripeptide hydrogel as a sorbent material for therapeutic drug monitoring and toxicological analysis via a simple, non-invasive and rapid approach for drug detection in oral fluids. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily causes mild to moderate respiratory illness in humans, but infection can also lead to long-term complications, including chronic fatigue, respiratory and cardiac issues, or even death. In November 2021, the emergence of the highly transmissible Omicron variant marked a significant shift in the pandemic, with its subvariants rapidly spreading and continuing to evolve worldwide. The continuing introduction of Omicron subvariants underscores the need for the development of up-to-date vaccines, as well as for appropriate animal models in which they can be evaluated. Among these subvariants, XBB.1.5 stands out for its ability to evade the immune response from previous infection or vaccination. The objective of this study was to determine the disease course in African green monkeys (AGMs) following intranasal exposure to the XBB.1.5 subvariant. In four intranasally exposed AGMs, histopathological findings in the lungs consistent with SARS-CoV-2 infection included lymphohistiocytic and neutrophilic bronchiolitis with variable numbers of syncytial cells, to terminal bronchiole-centric, bronchointerstitial pneumonia with alveolar type II (AT2) pneumocyte hyperplasia, with evidence of acute alveolar injury, including alveolar septal necrosis and hyaline membrane formation. The two males showed more severe pneumonia compared to the two females. SARS-CoV-2 RNA was detected in the lungs or tracheobronchial lymph nodes in the males but not in the females, which correlated with higher cumulative lung pathology scores in the males. In the females, SARS-CoV-2 RNA was limited to the colon and nasal turbinates. Our results indicate that AGMs exhibit a disease course similar to most humans when exposed intranasally, making them a suitable model for studying mild to moderate SARS-CoV-2 infection. Therefore, further work is warranted to determine if this model could have utility for the evaluation of vaccine and therapeutic candidates against contemporary SARS-CoV-2 variants. Full article

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-infectious complication of SARS-CoV-2, often with cardiac involvement. Myocardial strain imaging may detect dysfunction missed by conventional echocardiography. The objectives of this study are to characterize cardiac manifestations of MIS-C and assess the value of strain imaging in children with preserved and reduced left ventricular ejection fraction (LV-EF). Methods: We retrospectively analyzed 22 MIS-C patients admitted between September 2020 and January 2024, all with cardiac involvement. Clinical, laboratory, and echocardiographic data—including 2D and speckle-tracking strain—were collected at the day of worst dysfunction (DWD) and discharge (DD) and compared with 22 matched controls. Results: Median age was 4.65 years; 59% male; 45% overweight/obese. LV systolic dysfunction (LV-EF < 50%) occurred in 54.5%, coronary abnormalities in 36.4%, and pericardial effusion in 95.5%. LV global longitudinal strain (LVGLS) was significantly lower than controls at the DWD (−15.45 ± 4.76%, p < 0.0001) and DD (−20.63 ± 4.66%, p = 0.014). Strain abnormalities persisted despite LV-EF recovery, and even patients with preserved LV-EF showed significant segmental strain reduction. LVGLS and apical infero-septal strain were strongest predictors of reduced LV-EF. Conclusions: MIS-C often causes systolic dysfunction and coronary changes, but strain imaging reveals persistent subclinical myocardial injury. Long-term cardiac monitoring is warranted. Full article