Search Results (1,018)

Pneumocystis is a respiratory fungal pathogen that causes life-threatening pneumonia in immunocompromised patients. While Pneumocystis can colonize healthy hosts by resisting and transiently evading innate immunity, a functional adaptive immune response is essential to prevent progressive infection. Impairments in adaptive immunity, particularly defects in CD4⁺ T cell function, are strongly associated with the development of severe Pneumocystis pneumonia (PCP) in humans and a wide range of mammalian species. Immune activation by Pneumocystis has strong genetic determinants, and a major gap in our understanding of PCP pathogenesis lies in uncovering the mechanisms by which Pneumocystis escapes alveolar macrophages and evades pulmonary innate immunity. Prior research determined that FVB/NJ mice display an unusual resistance to Pneumocystis infection. Further susceptibility testing across several inbred mouse strains revealed that the AKR/J strain, which is phylogenetically distant from the FVB/NJ strain, also exhibits a rarely described form of protective innate immunity against PCP. Notably, the mechanism of AKR/J resistance does not require CD4⁺ or CD8⁺ T lymphocytes. However, depleting alveolar macrophages prior to infection rendered AKR/J mice susceptible to PCP, highlighting the critical role of macrophages for this protective innate immune response. These novel findings establish the AKR/J inbred strain as a valuable model for investigating the interaction between Pneumocystis and macrophages, offering a unique opportunity to explore how these interactions lead to differential outcomes between resistant and susceptible mouse strains. Additionally, it may offer key insights into the mechanisms by which Pneumocystis evades macrophage-mediated innate immunity in the majority of mammalian hosts, including humans. Full article

Background/Objectives: Evidence suggests that modifiable lifestyle interventions improve disability in relapsing multiple sclerosis (MS); however, interactions between different factors may impact outcomes. Thus, the objective of this secondary analysis was to investigate diet-induced effects on the impact of MS and effect modification by other modifiable lifestyle factors. Methods: The physical and psychological impact of MS was assessed with the MS Impact Scale-29 (MSIS) at run-in, baseline, 12 weeks, and 24 weeks. Participants were randomized at baseline to the Swank low-saturated fat or Wahls modified Paleolithic elimination diets and instructed to maintain usual physical activity, objectively measured with an accelerometer, throughout the trial. Baseline information on sleep, physical activity, alcohol, and smoking was explored as effect modifiers. Results: Among the Swank group, MSIS-Physical scores improved from 33.8 ± 3.8 at baseline to 28.7 ± 3.6 at 12 weeks (p = 0.04) and 25.3 ± 3.5 at 24 weeks (p < 0.001). MSIS-Psychological scores also improved from 35.7 ± 3.3 at baseline to 25.6 ± 2.6 at 12 weeks (p = 0.001) and 22.8 ± 2.4 at 24 weeks (p < 0.001). Among the Wahls group, MSIS-Physical scores improved from 33.8 ± 3.1 at baseline to 21.7 ± 3.0 at 12 weeks (p < 0.001) and 19.0 ± 3.1 at 24 weeks (p < 0.001). MSIS-Psychological scores also improved from 38.4 ± 3.8 at baseline to 25.5 ± 3.8 at 12 weeks (p < 0.001) and 20.6 ± 3.6 at 24 weeks (p < 0.001). Improvements in MSIS-Physical were greater among participants who were physically inactive or drank little alcohol at baseline. Conclusions: Both diets led to favorable within-group improvements in the perceived impact of MS. People with MS who are physically inactive or drink little alcohol may benefit the most from dietary interventions. Full article

The lack of integrity at the implant–abutment junction (IAJ) contributes to problems such as micromovements and microbial colonisation. This study aimed to (1) design a protocol for assessing microleakage at the IAJ using chromophore analysis not previously reported for this specific application, (2) compare gas and dye leakage between titanium (Ti) and cobalt chrome (CoCr) abutments, and (3) assess the effect of gold (Au) gilding on sealing. Forty abutments were divided into five groups: milled Ti (MTi); cast CoCr (CCoCr); milled CoCr (MCoCr); cast CoCr with Au gilding (CCoCrG); and milled CoCr with Au gilding (MCoCrG). Samples were subjected to internal pressure within a gas and dye reservoir. Chromophore analysis via UV-Vis spectrometer was used to calculate crystal violet leakage concentrations. Scanning electron microscopy (SEM) revealed close adaptation in the MTi and MCoCr groups, contrasting with irregularities in the CCoCr groups. Correspondingly, gas leakage and dye leakage were most prevalent in the CCoCr group. Fisher exact test demonstrated a statistically significant difference (p = 0.026) between the MCoCr and CCoCr abutments. While CCoCr exhibited the highest failure rate (62.5%), Au gilding demonstrated a trend toward reduced leakage (25% failure rate), though this did not reach statistical significance (p = 0.315). This chromophore analysis represents a viable and objective assessment of IAJ integrity. Full article

The accurate measurement of spheroid area and morphology is critical for the progression of the integration of 3D models in in vitro cancer research and is increasingly used to measure effective therapeutic efficacy of X-ray radiation. Current methods of measuring spheroids require labour-intensive manual analysis or the use of complex software tools. SphereMetrics was created as a user-friendly Shiny app with a straightforward interface designed to streamline the process of measuring the area and eccentricity of spheroids. It allows the upload and automated detection of spheroids across multiple file formats and generates robust and objective area and eccentricity measurements. Area measurements derived from SphereMetrics were compared to manual quantification with ImageJ and AnaSP for untreated and irradiated (0–20 Gy) human neuroendocrine BON-1 cancer spheroids. When compared to ImageJ and AnaSP, SphereMetrics was shown to provide fast, accurate data (R² = 0.87 and 0.83, respectively). Spheroid analysis took 19.92 ± 8 s/image with SphereMetrics, approximately four times faster than ImageJ analysis (89.81 ± 11.52 s/image) and nine times faster than AnaSP (183.36 ± 31.62 s/image). SphereMetrics represents an accessible and efficient tool for spheroid analysis, facilitating data collection and analysis for routine in vitro model research, ideal for non-programmers. Full article

Background/Objectives: Nosocomial outbreaks of viral respiratory infections strain healthcare systems and endanger patients and healthcare workers (HCWs). We describe two large nosocomial outbreaks with the SARS-CoV-2 Alpha variant, during its initial emergence in Germany, to assess transmission dynamics, effectiveness of control measures, and challenges in managing highly transmissible respiratory viruses. Methods: Confirmed cases were inpatients, HCWs, or their contacts testing SARS-CoV-2-positive since 1 January 2021 (Hospital A [HA])) or 21 January 2021 (Hospital B [HB])) with N501Y and delH69/V70 spike gene mutations. We conducted case interviews, reviewed medical records and shift schedules, and performed sequencing, genome reconstruction, and phylogenetic analysis. We describe cases, transmission chains, and control measures. Results: HA reported 18 patient cases, 20 HCW cases, and 33 community cases (N = 71). HB reported 48 patient cases, 43 HCW cases (13 in a COVID-19 ward), and 27 community cases (N = 118). In-hospital transmission occurred patient-to-patient, HCW-to-patient, patient-to-HCW, and HCW-to-HCW. HA halted admissions immediately after the initial cases; HB implemented measures gradually. Regular testing detected pre-symptomatic (HA = 6; HB = 18) and asymptomatic cases (HA = 3; HB = 13). Testing of agency staff was incomplete. The suspected primary case was an HCW in HA and a patient in HB who required resuscitation shortly after admission. Conclusions: Early COVID-19 outbreaks offer valuable lessons for managing emerging nosocomial outbreaks of highly transmissible respiratory viruses. Our findings provide empirical evidence for effective interventions, including rapid response, testing, HCW protection, and rigorous contact tracing in high-risk emergency situations. Managing agency staff remains a major challenge. Full article

Background: Mass spectrometry (MS)-based immunopeptidomics has emerged as the gold standard for profiling HLA-bound peptides, yet detection remains challenging due to their non-tryptic nature, variable lengths, and lack of basic residues, which limit ionisation and fragmentation efficiency. Methods: To address these limitations, we investigated the impact of incorporating 5% dimethyl sulfoxide (DMSO) into LC-MS/MS mobile-phase buffers on immunopeptidomic workflows. Using B-lymphoblastoid cell lines expressing HLA class I and II alleles and elastase-digested HeLa lysates as a surrogate for non-tryptic peptides, we assessed peptide identification, ionisation efficiency, charge state distribution, and fragmentation quality. Results: DMSO significantly increased peptide identifications across all sample types, with gains of ~1.33 folds for HLA class I, ~1.55 folds for HLA class II, and ~1.24 folds for elastase digests. Improvements were systematic and reproducible, driven by enhanced electrospray ionisation, higher charge states, and superior MS2 spectral quality, evidenced by ~2-fold increase in b- and y-ion intensities. Importantly, DMSO did not introduce major sequence bias, preserving motif integrity and predicted binding characteristics. Conclusions: Overall, these findings establish DMSO as a robust additive for improving sensitivity and reliability in immunopeptidomics, particularly for low-input or clinically derived samples. Full article

The influence of Ni and Co additions on microstructure and mechanical properties of (CoCrCuTi)_100−xFe_x high-entropy alloys (HEAs) containing 10 or 15 at. % Fe was investigated. The base HEA consisted of dendritic C14 Laves phases with interdendritic Cu-rich FCC regions. When Ni in the range of 2.5 to 10 at. % was added, a reduction in the Cu-rich phase was observed. Conversely, Co additions in the same range initially increased the Cu-rich phase but eventually led to liquid-phase separation (LPS), forming distinct Cu-lean L1 liquid and Cu-rich L2 globular regions. The average Vickers hardness values of (CoCrCuTi)₉₀Fe₁₀ and (CoCrCuTi)₈₅Fe₁₅ HEAs were measured at 790 ± 33 HV and 760 ± 20 HV, respectively. The additions of Ni and Co decreased overall hardness values. However, while Ni additions caused greater microstructural refinement, Co additions eventually led to heterogeneity due to LPS. For instance, the Vickers hardness of (CoCrCuTi)₉₀Fe₁₀ with 2.5 at. % Ni reached a maximum of 706 ± 95 HV, decreasing in hardness and scatter to 646 ± 19 HV when Ni increased to 10 at. %. In contrast, Co additions led to a marked reduction in hardness, from 574 ± 114 HV at 2.5 at. % Co to 442 ± 246 HV at 10 at. % Co. The fracture toughness (KIC), determined using Vickers indentation testing, indicated that Ni additions reduce fracture toughness, while Co additions increase it. Full article

Three-dimensional (3D) bioprinting provides new options for airway reconstruction by enabling the fabrication of customizable, biodegradable scaffolds designed to support in situ tissue regeneration. Building on our established large-animal platform, in which two cm bioprinted tracheal grafts combined with refined surgical techniques and adjunctive laser intervention have achieved long-term survival exceeding three months, the present study aims to explore long-segment (≥four cm) tracheal transplantation. We evaluated the fabrication feasibility and regeneration patterns of extrusion-based 3D bioprinted polycaprolactone (PCL) tracheal grafts in a porcine model. The grafts were implanted via end-to-end anastomosis with adjunctive mechanical stabilization and followed by serial bronchoscopic surveillance, gross examination, and histological analysis. The two cm PCL tracheal grafts achieved reproducible survival exceeding three months when combined with refined surgical techniques, structured postoperative airway management, and optimized wound coverage. Histological analysis revealed multi-lineage tissue formation—including cartilage, muscle, glands, and epithelium—was observed. Cartilage regeneration followed a staged maturation process, compared to epithelial regeneration, although continuous by 12 weeks, remained developmentally immature. A single long-segment transplantation was explored in a single preliminary case, providing an initial technical observation of feasibility; however, definitive conclusions regarding long-term survival or regeneration cannot be drawn. These findings further characterize regenerative responses in a large-animal model and highlight critical translational barriers—fabrication constraints, airway biomechanics, and delayed epithelial maturation—that require systematic investigation before long-segment tracheal reconstruction can advance toward clinical application. Full article

This study evaluated entomopathogenic nematodes (EPNs) isolated from a cacao agroforestry system in the Peruvian Amazon, focusing on their molecular characterization and efficacy against Spodoptera frugiperda (Lepidoptera: Noctuidae) larvae. Thirteen EPN isolates were obtained from 50 soil samples using the Galleria mellonella baiting technique. Mortality assays revealed significant differences among isolates at 24, 48, and 72 h, with isolates 11N-A4 and 8N-B1 being the most virulent, achieving maximum mortalities of 100% and 96.3% at 72 h, respectively. Median lethal time (LT₅₀) values indicated rapid action of these isolates on G. mellonella larvae, with 33.3 h for 11N-A4 and 32.4 h for 8N-B1. Molecular identification using ITS, D2–D3 (LSU), and COI markers confirmed the isolates as Heterorhabditis sp. (11N-A4) and Heterorhabditis amazonensis (8N-B1). In bioassays with S. frugiperda larvae, both EPNs exhibited dose- and time-dependent mortality. H. amazonensis showed rapid action, reaching 100% mortality at the highest dose (60 IJs/larvae) within 48 h, whereas Heterorhabditis sp. displayed a gradual, sustained increase, attaining 91% mortality at 72 h. Median lethal dose (LD₅₀) and LT₅₀ values reflected the efficiency of both isolates, with Heterorhabditis sp. achieving lower LD₅₀ at later stages and shorter LT₅₀ at low-to-intermediate doses. These findings highlight the potential of Heterorhabditis sp. and H. amazonensis as effective biocontrol agents adapted to local conditions and represent the first report of H. amazonensis in Peru. Further studies under field conditions are required to confirm their suitability for incorporation into integrated pest management strategies in the Peruvian Amazon. Full article

The image of the journalist in popular culture has increasingly added value to metajournalistic discourse. These portrayals have the power to influence the audience’s perception of real-world journalists and the industry. However, most research analyzes portrayals in film and television. Using Terry Pratchett’s fantasy novel “The Truth,” this study explored how journalism, the media industry, and the journalist are portrayed in fantasy literature. Through a textual analysis of the novel, it was found that the work was a celebratory portrayal of journalism that shared a variety of themes found in film and television portrayals. Though its ethics were challenged throughout the novel, the Ankh-Morpork Times was devoted to the truth, served the watchdog role, and practiced social responsibility. Additionally, the novel’s historical rendition of the penny press highlighted the competitiveness of the media industry, how the public interest was challenged by political and corporate influence, and offered a portrayal of naïve news consumers. Lastly, it was found that William de Worde portrayed an ethical journalist and followed the common investigative journalist trope, but his character strayed from the usual editor, publisher, and male reporter tropes found in film and television. This study also suggests the possibility of looking at negative portrayals of journalism in fiction as a series of critical incidents in which journalism has difficulty fully repairing its paradigm. Full article

Soil heterogeneity and acidity are major constraints to Coffea arabica production in the Amazonian soils of Peru. This study developed a spatial predictive framework that integrates a weighted Soil Quality Index (SQIw) and geostatistical modelling (Regression–Kriging and Ordinary Kriging) to estimate lime requirements (LRs) and delineate management zones. A total of 69 coffee-cultivated soil samples were analysed, and spectral information (NDVI) was incorporated to estimate relative yield (RR). Multivariate analysis defined a Minimum Data Set (MDS) composed of exchangeable Na, available P, pH and silt percentage; the highest weights were assigned to P (Wi = 0.292) and pH (Wi = 0.276). SQIw exhibited wide variability (0.01–0.87; CV = 51.8%) and was grouped into five classes, with low (43.5%)- and very low (21.7%)-quality classes predominating. SQIw showed a strong relationship with RR (r = 0.64). Geostatistical models performed differently between localities: in Nuevo Huancabamba, Regression–Kriging improved prediction accuracy (SQIw: R² = 0.58; LR: R² = 0.396), whereas in San José de Sisa, Ordinary Kriging provided better fits only for LRs (R² = 0.32). Nuevo Huancabamba is dominated by moderate-to-high-quality soils (87.29%; SQIw > 0.6) and low lime requirements (74.94%; <0.84 t ha⁻¹), in contrast with San José de Sisa, where low-quality soils prevail (89.45%; SQIw < 0.4) alongside high LRs (75.26%; 2.54–7.13 t ha⁻¹). The resulting maps enable targeted interventions—precision liming and focused P fertilisation—to correct acidity and phosphorus deficiency, thereby improving input-use efficiency and enhancing the sustainability of Amazonian coffee systems. Full article

Adverse weather removal aims to restore images degraded by haze, rain, or snow. However, existing unified models often rely on implicit degradation cues, making them vulnerable to inaccurate weather perception and insufficient semantic guidance, which leads to over-smoothing or residual artifacts in real scenes. In this work, we propose AWR-VIP, a prior-guided adverse weather removal framework that explicitly extracts semantic and perceptual priors using a frozen vision–language model (VLM). Given a degraded input, we first employ a degradation-aware prompt extractor to produce a compact set of semantic tags describing key objects and regions, and simultaneously perform weather-type perception by prompting the VLM with explicit weather definitions. Conditioned on the predicted weather type and selected tags, the VLM further generates two levels of restoration guidance: a global instruction that summarizes image-level enhancement goals (e.g., visibility/contrast) and local instructions that specify tag-aware refinement cues (e.g., recover textures for specific regions). These textual outputs are encoded by a text encoder into a pair of priors (${\mathbf{P}}_{global}$ and ${\mathbf{P}}_{local}$), which are injected into a UNet-based restorer through global-prior-modulated normalization and instruction-guided attention, enabling weather-adaptive and content-aware restoration. Extensive experiments on a combined benchmark show that AWR-VIP consistently outperforms state-of-the-art methods. Moreover, the VLM-derived priors are plug-and-play and can be integrated into other restoration backbones to further improve performance. Full article

Background: Heart rate variability (HRV) is a valuable indicator for assessing vascular health, but keeping clinical decision support systems (CDSSs) aligned with the rapidly evolving literature remains challenging. This study aimed to develop an LLM-assisted literature synthesis framework to support transparent HRV-based risk stratification, enabling systematic extraction and organization of HRV evidence from published studies. Methods: An LLM-driven framework was developed to extract HRV parameters from 140 medical abstracts. The system simulated step-by-step human reasoning to identify key HRV indicators and group patient data using predefined statistical thresholds derived from the literature. System performance was evaluated using ECG-derived HRV features as a feasibility evaluation of literature-guided HRV classification. Results: The proposed framework demonstrated an accuracy of 86% in literature-guided HRV classification, with a sensitivity of 81% and a specificity of 87%. Compared with traditional machine learning approaches, the LLM-assisted system provided transparent, literature-grounded reasoning and could be readily updated as new studies became available. Conclusions: Large language models can support evidence-guided parameter selection and feasibility-level HRV-based risk stratification, rather than serving as predictive classifiers. This approach reduces manual effort, enhances transparency, and addresses common “black box” concerns associated with AI-assisted CDSS development in clinical practice. Full article

Hydrothermal carbonised waste (hydrochar) is increasingly considered a sustainable soil amendment within circular economy frameworks; however, its toxicity to the environment limits its safe application. Ageing and pyrolysis may be prospective treatments to mitigate hydrochar toxicity on soil organisms and plants, but their effectiveness is unresolved since available studies did not investigate the predominantly toxic hydrochars, those produced at high reaction temperatures (>200 °C). In this study, toxic hydrochars produced at hydrothermal carbonisation (HTC) temperature of 260 °C from biosolids, chicken manure and rice straw were post-treated by in situ ageing in soil for 30 days or by pyrolysis at 400 °C for 30 min, and their toxicity was assessed on wheat growth and earthworm (Eisenia fetida) avoidance. Untreated hydrochars did not affect wheat (Triticum aestivum L.) germination, but reduced wheat growth by 23–33%, and caused 82–94% earthworm avoidance. The ageing of hydrochar reduced phytotoxicity in biosolids and chicken manure hydrochar treatments, as indicated by improved wheat biomass (25–71%; compared to untreated hydrochar). Ageing of hydrochar also mitigated toxicity to earthworms, as indicated by the reduced avoidance of 19–31% across all feedstocks. The persistent phytotoxicity with aged rice straw hydrochar was due to toxic organic compounds that could not be fully detoxified after 30 days of ageing. Pyrolysis of hydrochar mitigated phytotoxicity as indicated by increased wheat biomass (43–93%), and reduced toxicity to earthworms (39–51%) across all feedstocks. Findings indicate that while both ageing and pyrolysis are appropriate hydrochar post-production treatments, ageing of hydrochar for only 30 days in soil may not fully alleviate the phytotoxic effect of all hydrochars. Full article