Search Results (1,295)

Background: Accurate identification of pneumonia pathogens is critical for guiding appropriate antibiotic therapy and minimizing unnecessary antimicrobial exposure. Bronchoalveolar lavage (BAL) is widely used for pathogen detection but introduces procedural risks. Bronchial washing (BW) is simpler and less invasive, yet evidence for its utility in multiplex PCR diagnostics is limited. Methods: This study includes an evaluation of the clinical utility of the BioFire^® FilmArray^® Pneumonia Panel (FA) using BW specimens via comparison with conventional culture. Between 2022 and 2024, 190 BW specimens were collected from 182 adult patients with suspected pneumonia at Eunpyeong St. Mary’s Hospital, Seoul, Korea. Each specimen was tested simultaneously using FA and conventional culture. Results: The culture positivity rate was 41.6%, whereas FA showed a higher positivity rate of 51.1%. Of all specimens, 52.6% (100/190) were positive in at least one of two methods, and 11.0% (21/190) were FA-positive only. FA detected 72 additional bacterial targets, most commonly H. influenzae, K. pneumoniae, S. aureus, S. agalactiae, and S. pneumoniae. Semi-quantitative results demonstrated a statistically significant moderate correlation with culture (ρ = 0.48, p < 0.001). Eight bacterial targets achieved 100% PPA, and resistance genes were rapidly detected, although some discrepancies with phenotypic antimicrobial susceptibility testing were observed. Several FA-only detections may reflect oropharyngeal colonization rather than true infection. Conclusions: FA testing of BW specimens demonstrated high concordance with culture and provided rapid pathogen and resistance gene detection. BW-based FA testing may serve as a useful diagnostic alternative when BAL is not feasible, although careful interpretation is required to account for potential contamination. Full article

Bacteriophages are powerful drivers of microbial evolution and are increasingly explored as alternatives to antibiotics against multidrug-resistant pathogens such as Pseudomonas aeruginosa. Here, we describe the isolation, phenotypic characterization and genomic, structural and evolutionary analysis of Pseudomonas phage Adele, a lytic myovirus representing a novel species within the genus Pakpunavirus (family Vandenendeviridae). Phage Adele exhibits a short latent period of 20 min, a burst size of 59 ± 11 virions per infected cell and a high virulence index, efficiently lysing non-O11 Pseudomonas aeruginosa strains and reducing biofilm biomass. In vivo, Adele confers marked protection in a Galleria mellonella infection model. Phylogenetic reconstruction, synteny analysis and structural modeling demonstrate the relatedness of Vandenendeviridae to phages of the Andersonviridae and Vequintavirinae clades, pointing to a stable, ancestral virion architecture that has undergone lineage-specific elaborations, including the duplication and divergence of tail tube proteins. The tail assembly chaperone gene employs a conserved -1 programmed ribosomal frameshift. Phage Adele encodes an elaborate set of metabolic reprogramming and anti-defense systems, reflecting extensive horizontal gene transfer. The combination of a conserved structural architecture and mosaic genome establishes Adele as an exemplary system for studying modular evolution in phages, alongside its demonstrated therapeutic efficacy. Full article

Background/Objectives: Prolonged fasting—defined as voluntary abstinence from caloric intake for periods exceeding 24 h—is increasingly recognized not only as a metabolic intervention but also as a psycho-behavioral modulator. According to the 2024 international consensus, intermittent fasting encompasses diverse temporal patterns including time-restricted feeding, alternate-day fasting, and periodic fasting of multi-day duration. While metabolic benefits are well documented, the psychoneurobiological and psychiatric consequences remain incompletely characterized. This review critically appraises current evidence on the psychological and psychiatric effects of prolonged and intermittent fasting, including both secular and religious practices. Methods: A narrative synthesis was conducted on clinical trials, observational studies, and translational research published between January 2010 and June 2025 in PubMed, Scopus, and PsycINFO. Search terms included combinations of “prolonged fasting,” “intermittent fasting,” “psychological,” “psychiatric,” “religious fasting,” “Ramadan,” and “Orthodox Church.” Eligible studies required explicit evaluation of mood, cognition, stress physiology, or psychiatric symptoms. Data were analyzed qualitatively, with particular attention to study quality, fasting regimen characteristics, and participant vulnerability. This is a non-registered narrative synthesis drawing on clinical trials, observational studies, and preclinical evidence published between January 2010 and June 2025. Results: Eighty-seven studies met inclusion criteria (39 human; 48 preclinical). In metabolically healthy adults, short-term time-restricted eating and supervised prolonged fasting were associated with modest reductions in depressive symptoms and perceived stress, with small improvements in executive functioning—typically observed in small samples and with limited follow-up. Religious fasting during Ramadan and the Orthodox Christian fasting periods demonstrated similar neuropsychological effects, including greater perceived spiritual meaning and affective modulation, though cultural context played a moderating role. Potential adverse mental-health impacts included mood destabilization, anxiety exacerbation, and rare psychotic or manic decompensations in vulnerable individuals. Randomized trials reported few adverse events and no signal for severe psychiatric harm, whereas observational studies more often noted symptom exacerbations in at-risk groups. Patients with eating disorder phenotypes exhibited increased cognitive preoccupation with food and a heightened risk of behavioral relapse. Methodological heterogeneity across studies—including variation in fasting protocols, psychological assessments, and follow-up duration—limited cross-study comparability. Conclusions: Evidence indicates a bidirectional relationship wherein fasting may foster psychological resilience in select populations while posing significant psychiatric risks in others. Inclusion of religious fasting traditions enriches understanding of culturally mediated outcomes. To enhance rigor and safety, future studies should incorporate clinician-rated outcomes (e.g., HDRS-17, CGI-S/CGI-I), standardized adverse-event tracking using validated psychiatric terminology, and prospective safety monitoring protocols, with ≥6–12-month follow-up. Full article

Organ-on-a-chip (OoC) or tissue-on-a-chip (ToC) technologies represent a significant advancement in enabling modeling of human organ and tissue physiology for medical study, although further development is required for these technologies to reach widespread adoption. OoC/ToC are three-dimensional (3D) microfluidic platforms that overcome limitations of traditional two-dimensional (2D) cell culture or animal models, providing an alternative environment for disease study, drug interactions, and tissue regeneration. The design of these systems is complex, requiring advanced fabrication techniques and careful selection of biomaterials with consideration of material toxicity, optical clarity, stability, and flexibility. A key innovation in this field is the multi-organ-on-a-chip (MOC) technology, which links multiple organ systems on a single platform. This enables the study of systemic diseases and the complex communication between organs, which is not possible with single-organ models. Furthermore, OoC/ToC technology holds immense potential for personalized medicine. By using patient-specific cells, these devices can create disease models that reflect an individual’s unique genetic and phenotypic variations, paving the way for tailored therapeutic interventions. The integration of real-time sensors within these devices also facilitates high-throughput screening and accelerates drug discovery. While the development and optimization of these systems is still in its early stages, OoC/ToC technologies have already demonstrated promise in a number of translational research applications. Full article

One major bottleneck for the sustainable development of the aquaculture sector is the reliance on conventional feed ingredients, such as fishmeal and soy protein. Another challenge is nutrient loss from these systems, which contributes to environmental pollution but also represents a waste of valuable resources. To make aquaculture truly sustainable, a shift toward circular, sustainable systems is necessary. This study compared a regionally available alternative feed, based on blue mussel meal and pea protein concentrate, to a conventional fish meal and soybean control diet in Nile tilapia (Oreochromis niloticus) reared in coupled aquaponic systems. Fish performance and stress levels, water quality, plant growth, and microbial quality were investigated. Growth performance and feed intake were similar between aquaponic and control recirculating aquaculture systems (RASs) during the control feed (CF) phase. Only the feed conversion ratio (FCR) was slightly lower in the aquaponic system during the mussel-pea feed (MPF) phase. Tatsoi (Brassica rapa) growth in the aquaponic systems was comparable to, or even greater than, that of the hydroponic control systems, throughout the experiment, especially during the MPF phase. In addition, the MPF had a positive impact on phenotypic parameters and contributed to enhanced shoot growth. However, the presence of pathogens with potential biohazard impacts on human and fish health remains a concern and warrants further investigation. In our study, Salmonella spp. was detected in both systems, but levels were considerably reduced with the MPF phase. In contrast, Escherichia coli was detected only in RASs and was absent from aquaponic systems. Overall, the findings support the potential of blue mussel and pea protein as sustainable, local feed components in integrated aquaponic production, contributing to nutrient circularity and reducing dependence on limited marine stocks and imported resources. Full article

Background: Computed tomography (CT) angiography is widely regarded as the gold standard for diagnosing acute aortic dissection. However, in patients with contraindications to iodinated contrast media, such as those with renal insufficiency or hemodynamic instability, non-contrast CT may offer a viable alternative for initial evaluation. Understanding the molecular mechanisms underlying aortic dissection, including extracellular matrix degradation, smooth muscle cell apoptosis, and inflammatory pathways, is crucial for developing novel diagnostic and therapeutic approaches. This report describes a single case of acute Stanford type A aortic dissection initially detected on non-contrast CT. Case Presentation: We describe a 74-year-old man who presented to the emergency department with fever and suspected infection, but without chest pain. An incidental finding on non-contrast CT revealed ascending aortic dilatation, pericardial effusion, and a suspected intimal flap. Subsequent CT angiography confirmed a Stanford type A aortic dissection. Conclusions: This case highlights the potential value of non-contrast CT in the early detection of aortic dissection, particularly when CT angiography cannot be performed. Recent advances in artificial intelligence (AI) and radiomic analysis have shown promise in augmenting the diagnostic capabilities of non-contrast CT by identifying subtle imaging features that may correlate with underlying molecular pathology and elude human observers. Emerging evidence suggests that radiomic features may reflect molecular alterations in the aortic wall, including metalloproteinase activity, collagen degradation, and inflammatory cell infiltration. Incorporating AI-assisted interpretation alongside insights into molecular mechanisms could facilitate earlier diagnosis, improve risk stratification, and guide personalized treatment strategies in critically ill patients. Although non-contrast CT has limited sensitivity for aortic dissection, it may still reveal crucial findings in selected cases and should be considered when contrast-enhanced imaging is not feasible. Ongoing progress in AI, radiomics, and molecular biomarker research may further expand the clinical applications of non-contrast CT in emergency cardiovascular care and bridge the gap between imaging phenotypes and molecular endotypes. These findings are hypothesis-generating and require validation in larger cohorts before clinical generalization. Full article

Adoptive cellular therapy with donor-derived T cells has always been an attractive strategy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to reduce the risk of relapse in acute myeloid and lymphoid leukemias. Donor lymphocyte infusion (DLI) is still the best-established option, especially in the preemptive phase when measurable residual disease (MRD) becomes positive and in the prophylactic setting—when MRD is not detectable. However, the clinical benefit of DLI is counterbalanced by the possible onset of graft-versus-host disease (GvHD), which continues to restrict its wide application. To address this challenge, several alternative cell-based strategies have been developed. One of these is represented by cytokine-induced killer (CIK) cells, generated from donor peripheral blood mononuclear cells through stimulation with anti-CD3 antibodies, interferon-γ, and interleukin-2. These cells are characterized by a hybrid phenotype, combining T-cell functions with natural killer-like properties, and exhibit antitumor activity in an MHC-unrestricted manner. CIK cells are generally well tolerated and associated with low toxicity but their efficacy is so far modest. Based on the experience of CAR-T in the treatment of B-cell lymphoid disease, CIK cells have been engineered with chimeric antigen receptors (CAR) developing the CARCIK cells. This novel cellular strategy represents a promising approach in the treatment of acute myeloid and lymphoid leukemia relapsed post-allo-HSCT. This review provides an overview of the current CAR-CIK experiences in the setting of acute leukemias and outlines future directions for their clinical translation. Full article

This study evaluated 362 chickpea accessions by analyzing the phenotypic variation of 17 major traits. The main agronomic traits and quality traits were comprehensively evaluated using principal component analysis (PCA) and cluster analysis. The results revealed a Shannon diversity index (H’) for the five qualitative traits ranging from 0.76 to 1.20, while for the twelve quantitative traits, it ranged from 1.45 to 2.07. The coefficient of variation (CV) ranged from 7.63% to 41.69%, demonstrating substantial variation and significant differences among the 362 germplasm resources. Correlation analysis revealed that traits such as growth period, plant height, seed weight per plant, and hundred-seed weight were closely correlated with yield. PCA extracted five principal components, collectively explaining 76.06% of the total variance, representing most of the agronomic traits and quality traits. Cluster analysis categorized the accessions into five distinct groups, which can be used as germplasm alternative materials with high yield, mechanization potential, large grain size, early maturity, stress resistance, and high protein content. Using a membership function, a comprehensive evaluation score (F-value) was calculated, leading to the identification of ten accessions with superior overall traits. These could be used as materials for breeding and germplasm creation of new chickpea varieties. This research provides a scientific basis for future parental selection in chickpea breeding programs and for the screening of specific chickpea germplasm resources. Full article

Synovial sarcoma (SySa) is a malignant soft tissue tumor that is characterized by an SS18::SSX fusion protein, which integrates into BAF chromatin remodeling complexes and alters global gene transcription. Despite its uniform genetic driver, SySa displays striking histomorphological and phenotypic heterogeneity, including spindle cell, glandular and poorly differentiated patterns. Prognosis is variable, with around 50% of patients developing metastases. Limited response to chemotherapy highlights the need for a better understanding of the underlying molecular mechanisms to guide alternative therapeutic strategies. Given the pivotal function of BAF complexes in SySa and their recently described impact on cellular differentiation processes, this study aims to investigate the role of SS18::SSX and specific BAF subunits in SySa differentiation. Nanostring analysis revealed that silencing of SS18::SSX and the GBAF subunit BRD9 modulates the cellular differentiation pathways. SS18::SSX and BRD9 were found to regulate epithelial–mesenchymal-transition (EMT)-associated factors of Snail and Slug on different levels, with SS18::SSX repressing E-Cadherin expression. Published single-cell RNA sequencing data were analyzed to validate our finding that BRD9 contributes to SySa EMT regulation. Our study provides novel insights into the multilayered regulation of key EMT players by SS18::SSX and BRD9 in SySa, thereby defining tumor phenotype and (potentially) prognosis. Full article

Activation through the T cell receptor (TCR) initiates a signaling cascade in T cells that induces extensive molecular and cellular changes. The adaptor protein Linker for Activation of T cells (LAT) plays an essential role in transducing activation and regulatory signals downstream of the TCR. Phosphorylation of LAT tyrosine residues recruits multiple signaling proteins, leading to the assembly of the LAT signalosome, which is crucial for relaying signals that regulate T cell development and function. We previously showed that substitution of a negatively charged amino acid segment preceding the fifth tyrosine residue of LAT (Tyr127 in humans or Tyr132 in mouse LAT) enhances some early TCR signaling events, whereas downstream responses, such as Ca²⁺ influx and Erk phosphorylation, are partially inhibited. To investigate the physiological relevance of this segment in vivo, we generated a new LAT knock-in mouse strain (Lat^NIL) in which the negatively charged segment was replaced with a non-charged sequence. Unexpectedly, this mutation led to an alternative splicing event in the Lat gene that excluded exons 6 and 7, resulting in a frameshift, a premature stop codon at residue 145, and the loss of the six C-terminal tyrosine residues of LAT. Homozygous Lat^NIL/NIL mice showed a phenotype similar to that of LAT-knockout and Lat^4YF mice (in which the four C-terminal tyrosines had been mutated to phenylalanine). Interestingly, homozygous Lat^NIL/NIL mice exhibited a distinct population of γδ T cells in lymphoid organs, which has not been observed in LAT-KO or Lat^4YF mice. These γδ T cells expressed higher levels of CD27 compared to those in wild-type and LAT-KO mice, suggesting altered activation or differentiation states. Together, these data highlight how subtle alterations in LAT structure can profoundly impact T cell signaling and lineage composition. Full article

Background/Objectives: Osteoporosis is highly prevalent and contributes substantially to morbidity and mortality, yet long-term concerns about pharmacologic therapies leave a major treatment gap. Soy isoflavones have been investigated as safer alternatives, but results across trials are inconsistent. A key unresolved issue is the equol-producer phenotype, the gut microbial ability to convert daidzein to S-equol, the most bioactive isoflavone metabolite, which may explain much of this variability. This narrative review synthesizes mechanistic, translational, and clinical evidence to clarify the potential skeletal relevance of S-equol. Methods: Literature was identified through PubMed and Scopus searches (January 2000–October 2025) for experimental, mechanistic, and clinical studies examining S-equol, estrogen receptor β (ERβ), and bone metabolism, with emphasis on equol-producing status, bone strength and bone microarchitecture. Results: S-equol acts as a high-affinity ERβ agonist with antioxidant and anti-inflammatory properties but lacks the carcinogenic or thrombotic risks linked to ERα activation. In estrogen-deficient rodent models, S-equol improves trabecular bone volume by 10–20%, increases trabecular number, and enhances biomechanical strength. These findings align with preclinical evidence demonstrating that S-equol preserves trabecular microarchitecture, enhances bone strength, and reduces bone turnover. A limited number of human trials show reductions in bone resorption by 20% at a daily dose of 10 mg S-equol. In contrast, trials of soy isoflavones in humans have produced inconsistent findings, partly because of substantial variability in equol-producer phenotype among participants and the reliance on dual-energy X-ray absorptiometry, which cannot distinguish trabecular from cortical compartments. Advanced bone imaging and microbiome-informed approaches enable the precise evaluation of S-equol’s skeletal effects on trabecular bone and cortical bone, separately. Conclusions: S-equol represents a promising model for “precision nutrition,” where microbiome, hormonal, and host factors converge with potential to prevent age-related bone fragility. Rigorous trials that integrate microbiome phenotyping and advanced imaging are needed to validate this approach, translate mechanistic promise into clinical benefit, and better define safety. Full article

With the growing demand for antibiotic-free and sustainable poultry production, plant-derived antimicrobials have emerged as promising alternatives. However, a systematic understanding of the combined effects of oregano essential oil (OEO) and Macleaya cordata extract (MCE) on the broiler gut microbiome remains lacking. This study employed an integrated “structure–function–phenotype” framework to investigate the individual and combined (OMS) effects of OEO and MCE on gut microecological remodeling and its coupling with host growth, metabolic, and immune phenotypes. A total of 960 one-day-old broiler chicks were individually weighed and then randomly allocated to four treatments using body-weight-stratified randomization, with 6 replicate pens per treatment and 40 birds per pen, to ensure similar initial body weight across groups. Over a 42-day trial, we evaluated growth performance, serum biochemistry, antioxidant status, and immune parameters. Compared to the control, the OMS treatment significantly enhanced average daily feed intake (ADFI) and average daily gain (ADG), increased serum total protein (TP), and decreased blood urea nitrogen (BUN), triglycerides (TG), total cholesterol (TC), and alkaline phosphatase (ALP). However, the feed-to-gain ratio (F/G) was also higher in the OMS group, indicating that the improvement in growth rate did not translate into enhanced feed efficiency but was primarily driven by increased feed consumption. OMS also improved overall antioxidant capacity and key enzyme activities, elevated immunoglobulin levels, and reduced pro-inflammatory cytokines. Notably, OMS maintained Lactobacillus dominance, enriched Bacteroides, Enterococcus, and Butyricicoccus, and reduced Escherichia–Shigella. Functional predictions via PICRUSt2 suggested enhanced metabolic pathways related to antioxidant and immune functions; however, these results represent inference-based predictions and should be interpreted cautiously. Overall, the combination of OEO and MCE exerted synergistic benefits on growth, physiological health, and gut microbiota, supporting its potential as a phytogenic strategy for antibiotic-free broiler production. Full article

Rare genetic ocular diseases represent a heterogeneous group of disorders that significantly impair visual function and quality of life. Despite their clinical relevance, many of these conditions remain insufficiently characterized due to complex molecular mechanisms and diagnostic limitations. Recent advances in molecular diagnostics, particularly Next-Generation Sequencing (NGS), have enabled comprehensive and accurate identification of pathogenic variants, offering novel insights into genotype–phenotype correlations and supporting precision medicine approaches. In parallel, the use of alternative biological matrices such as tear fluid has emerged as a promising non-invasive strategy for biomarker discovery and disease monitoring. Tear-based omics, including proteomics and transcriptomics, have identified diagnostic signatures and pathogenic mediators such as non-coding RNAs, microRNAs, and tRNA-derived fragments (tRFs). Among these, tRF-1001 has shown potential both as a biomarker and therapeutic target in ocular neovascular conditions through its modulation of angiogenic pathways. The objective of this review is to show the integration of two rapidly advancing yet frequently isolated fields: next-generation sequencing-based genomics and tear-fluid molecular profiling, positioning them as complementary foundations of precision ophthalmology for rare inherited retinal and optic nerve disorders. Previous reviews have mainly concentrated on either genetic diagnosis or ocular surface biomarkers separately; however, we have introduced a convergent model wherein genomic data furnish diagnostic and prognostic clarity, while tear-omics deliver dynamic, minimally invasive assessments of disease activity, treatment efficacy, and persistent neurovascular stress. By explicitly connecting these two aspects, we have delineated how multi-matrix, multi-omics approaches can expedite early diagnosis, facilitate personalized longitudinal monitoring, and direct focused treatment interventions in rare ocular genetic illnesses. Full article

Pesticides have been extensively used in agriculture, forestry, and veterinary medicine under intensive production systems. Unfortunately, pesticide pollution resulted in a significant decline in non-target organisms, for instance, in detritivores such as necrophagous insects. Even formulations proposed as less harmful alternatives, such as neonicotinoids like imidacloprid (IMI), have been demonstrated to permeate the trophic chain and trigger severe consequences on non-target species. Here, the intra- and inter-generational effects of a sublethal dose of IMI were explored in the necrophagous greenbottle fly, Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae). This is because it has been demonstrated that the carcasses of domestic and wild animals can be contaminated with levels of these neonicotinoids. Transgenerational effects, extending up to three generations after a focal application of the pesticide on laboratory-cultivated F₁ flies, were investigated in this study. Morphological, demographic, and phenological features were evaluated through various analyses, including general linear mixed models (GLMM) and Haldane units analyses. Although GLMM showed no significant differences between treatments for the multiple traits observed, a significant directional microevolutionary trend of increased average imago and pupal size was identified for the IMI treatment through Haldane unit analysis. This microevolutionary change falls within the threshold of transgenerational phenotypic plasticity, a crucial mechanism for adaptive responses to environmental stressors. Among the possible explanations for this pattern, it is proposed that this is a likely consequence of the triggering of an epigenetic hormetic transgenerational change. This may contribute to explaining the development of adaptation and resistance towards pesticide formulations in a few generations after focal exposure. In addition to this idea, other possible mechanisms and consequences that explain the observed pattern are discussed. Overall, this experiment highlights the concerns of pesticide spillover consequences, even from sublethal doses of these formulations. Full article

Automated three-dimensional plant phenotyping is an essential tool for non-destructive analysis of plant growth and structure. This paper presents a low-cost system based on stereo vision for depth estimation and morphological characterization of maize plants. The system incorporates an automatic detection stage for the object of interest using deep learning techniques to delimit the region of interest (ROI) corresponding to the plant. The Semi-Global Block Matching (SGBM) algorithm is applied to the detected region to compute the disparity map and generate a partial three-dimensional representation of the plant structure. The ROI delimitation restricts the disparity calculation to the plant area, reducing processing of the background and optimizing computational resource use. The deep learning-based detection stage maintains stable foliage identification even under varying lighting conditions and shadowing, ensuring consistent depth data across different experimental conditions. Overall, the proposed system integrates detection and disparity estimation into an efficient processing flow, providing an accessible alternative for automated three-dimensional phenotyping in agricultural environments. Full article