Search Results (15,334)

This study evaluated the efficacy of the TOF-SIMS (time-of-flight secondary ion mass spectrometry) technique for the comprehensive lipidomic analysis of human meibum, a lipid-rich secretion essential for tear film stability, using samples collected from ten participants. The applied methodology proved effective in characterizing the complex chemistry of meibum, confirming the presence of diverse lipid classes, including fatty acids, sterols, and glycerolipids. Multivariate and pairwise statistical analyses, including permutational multivariate analysis of variance (PERMANOVA) and maximum mean discrepancy (MMD),confirmed the significant compositional difference between the two groups. Principal component analysis (PCA) revealed a clear separation between the samples, driven primarily by an elevated ratio of monounsaturated fatty acids (C18:1, C16:1) to cholesterol in the group with MGD compared to healthy controls. These findings demonstrate the utility of TOF-SIMS coupled with multivariate analysis for detecting disease-specific molecular alterations in meibum, highlighting its potential for differentiating ocular surface pathologies. Full article

Tenacibaculosis is a major bacterial disease in aquaculture, with Tenacibaculum discolor being characterized as one of the causative agents. This study evaluated the antimicrobial and antibiofilm potential of three isolated Pseudoalteromonas strains—Pseudoalteromonas sp. GY795-2 (deep-sea), Pseudoalteromonas spongiae MB2 (aquaculture installation), and Pseudoalteromonas tetraodonis SAE 20 (kelps)—against T. discolor strain FMCC B487. Cell-free supernatants (SNs) from each Pseudoalteromonas culture were tested in microtiter assays, assessing planktonic growth measured by OD₆₀₀ and biofilm biomass quantified by crystal violet (CV) staining. The addition of the Pseudoalteromonas SNs affected both growth and biofilm development of T. discolor strain FMCC B487. A significant decrease in T. discolor strain FMCC B487 growth and biofilm was observed in the presence of P. spongiae MB2 SN, whereas the SN of Pseudoalteromonas sp. GY795-2 promoted both growth and biofilm development of T. discolor strain FMCC B487. To assess whole-cell activity, dual-species biofilms were formed on plastic surfaces. After 24 h, all three Pseudoalteromonas strains reduced the viable T. discolor strain FMCC B487 population while maintaining their own cell numbers comparable to single-culture controls, suggesting an inhibitory interaction. These results demonstrate that these Pseudoalteromonas strains’ metabolites and cells can modulate T. discolor growth and biofilm development, highlighting their potential as biocontrol agents in aquaculture. Full article

Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors with significant biological diversity. Despite significant improvements in diagnostics and a growing range of available therapies, long-term disease control remains difficult in advanced cases. The tumor microenvironment, which in pNENs adopts a predominantly immunosuppressive profile and promotes tumor development, is attracting increasing attention. A complex network of interactions dominates the tumor tissue, including M2 macrophages, regulatory T cells, and numerous pathways that inhibit effector lymphocyte activity. M2 macrophages, through the secretion of anti-inflammatory cytokines and exosome-mediated signaling, support angiogenesis while simultaneously attenuating the cytotoxic response. Simultaneously, receptors and ligands associated with immune checkpoints are overexpressed. In addition to classic molecules such as PD-1/PD-L1 and CTLA-4, the role of B7x and CD276 is increasingly being emphasized, as their presence correlates with rapid disease progression and poor prognosis. To date, attempts to use checkpoint inhibitors as monotherapy have yielded modest clinical benefits. However, approaches based on combination strategies—both in the form of dual immune blockade and in combination with chemotherapy or angiogenesis-targeted therapy—have shown significantly greater activity. Therapies using tyrosine kinase inhibitors, such as sunitinib and newer drugs (lenvatinib, surufatinib, cabozantinib), may partially normalize the tumor’s disrupted vascular architecture and thus increase its susceptibility to immunological interventions. In the coming years, it will be crucial not only to overcome the immunosuppressive nature of the TME but also to identify predictive biomarkers that will allow for more precise patient selection. This approach may open the way to more effective, personalized therapies for pNENs. Full article

Background/Objectives: Thymomas are the most common tumors of the anterior mediastinum. While early-stage disease often has a favorable prognosis, therapeutic options in advanced stages remain limited. Moreover, the molecular profile of thymomas is still poorly characterized. In the present study, we explored the presence of targetable mutations and programmed death-ligand 1 (PD-L1) expression in a cohort of surgically resected thymomas. Furthermore, we investigated the correlation between PD-L1 expression, histological subtype, and risk of recurrence in patients who underwent curative-intent thymectomy. Methods: Mutational profiling was performed using a DNA-based NGS Cancer Panel of 16 genes. PD-L1 expression was evaluated via Tumor Proportion Score (TPS), and thymomas with TPS ≥ 50% were identified as high expressors. The associations with histological subtype and disease-free survival (DFS) were analyzed using logistic regression, Cox proportional hazards models, and Kaplan–Meier survival curves. Results: In our study, 2/37 (5.4%) of tested neoplasms (type AB and B2 thymoma) reported as a PIK3CA mutation; no other targetable mutations were observed. Moreover, high PD-L1 expression (≥50%) was reported in (15/37) 40.5% of patients and was significantly associated with aggressive histological subtypes (B2 and B3) (p < 0.001). Logistic regression analysis showed that high PD-L1 expression was a significant predictor of aggressive histology (McFadden’s R² = 0.268, p < 0.001), with an odds ratio of 15.5 (95% CI: 2.9–83.4; p = 0.001). During follow-up, 5/37 (13.5%) of patients experienced disease recurrence; however, no significant difference in DFS was found between high and low PD-L1 expression groups. Conclusions: Our data confirm the presence of PIK3CA mutations in thymomas and encourage the exploration the potential role of molecular target therapy in this setting. Moreover, we underlined that high PD-L1 expression level is associated with more aggressive thymoma subtypes and may have a role as a prognostic biomarker. These findings support the need for further studies on the potential role of molecular and predictive pathology in thymic epithelial tumors. Full article

Following the COVID-19 pandemic, researchers have increasingly focused on monitoring the spread of the virus and improving methods to detect changes in the SARS-CoV-2 genome. Although clinical surveillance provides direct and reliable results, it has limited applicability. Wastewater-based epidemiology (WBE) has therefore emerged as a valuable, non-invasive complementary tool for disease surveillance. It provides a comprehensive picture of virus circulation in a population, including asymptomatic individuals and those who do not seek healthcare. In addition, it facilitates early detection of outbreaks and the collection of epidemiologic data at the community level. However, WBE also presents technical challenges, including variations in sampling and testing protocols, the presence of inhibitors that affect viral RNA extraction, and the need for standardised procedures between studies. These challenges should be addressed for possible future infectious disease outbreaks. One of the challenges facing researchers was to develop efficient methods that could overcome the extraction and detection problems related to inhibitors present in wastewater. To this aim, this systematic review highlights the potential use of WBE, the variety of techniques, and the most effective methods for the detection and quantification of SARS-CoV-2 in wastewater samples. A reproducible electronic search of the literature was conducted in the Web of Science (WoS) and PubMed databases for articles published between 2020 and 2024. Our search revealed that the majority of observed WBE applications emphasised a correlation between SARS-CoV-2 RNA concentration trends in wastewater and epidemiological data. Another relevant issue that the articles often discussed and compared was the techniques used in different steps of sample processing, such as sample collection, concentration and detection, hence the lack of standardised procedures. This paper provides a framework regarding previous research on WBE to gain a better understanding that will lead to functional solutions. Full article

Background: Human polyomavirus JC (JCV) causes progressive multifocal leukoencephalopathy (PML), a deadly brain demyelinating illness stemming from oligodendrocyte lytic infection in immunocompromised patients, especially those with untreated HIV infection. Methods: We conducted a case series report on patients with HIV/AIDS who presented progressive multifocal leukoencephalopathy and were hospitalized at the “St. Parascheva” Clinical Hospital of Infectious Diseases in Iasi, northeastern Romania, to emphasize the comorbidities of HIV/AIDS cases. Hospital medical data from 10 January 2025 to 30 September 2025 served as the basis for this investigation. Results: We examined three cases that presented neurological symptoms (ataxia, aphasia, language comprehension, and expression disorders). The cases were evaluated imagistically via nuclear magnetic resonance, and we conducted a polymerase chain reaction test on the spinal fluid to confirm the presence of JCV. It was necessary to take a multidisciplinary approach with a neurologist or pneumologist. All cases were evaluated immunologically, revealing low Ly T CD4 levels and increased HIV viremia levels. Progressive multifocal leukoencephalopathy is an AIDS-defining disease, manifesting in immunocompromised patients, including late presenter cases, and patients who are non-adherent to their antiretroviral treatment. Therefore, it is important to test every patient who has mild to severe neurological symptoms for HIV. Furthermore, some cases require a multidisciplinary approach to ensure a better quality of life. Conclusions: Treating a patient with HIV requires a multidisciplinary strategy that includes a neurology specialist and access to antiretroviral treatment. To boost ART uptake, we must identify and remove barriers that impact patients and the healthcare system. Full article

Urinothorax, the presence of urine in the pleural space, is an exceptionally rare cause of pleural effusion, with fewer than 100 cases described in the literature. It most often follows trauma or urological procedures, though obstructive uropathy is also a recognized mechanism. We report an 83-year-old man with chronic kidney disease and benign prostatic hyperplasia who presented with acute dyspnea and a massive right-sided pleural effusion. Thoracentesis yielded clear yellow fluid with an ammonia-like odor, while imaging revealed chronic bladder outlet obstruction with bilateral hydroureteronephrosis. Despite inconclusive scintigraphy, the effusion resolved completely after urinary decompression with Foley catheterization, confirming the diagnosis. This case underscores the diagnostic challenges of urinothorax, which may be overlooked due to its rarity and variable biochemical profile, and highlights the importance of correlating clinical, radiologic, and pleural fluid findings. Early recognition is crucial, as timely relief of urinary obstruction provides both definitive diagnosis and curative treatment. Full article

The highly destructive pathogenic processes in patients with periodontitis are attributed to the presence of subgingival biofilms comprising key periodontal pathogens, such as Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as well as other periodontopathogens including Fusobacterium nucleatum, Selenomonas spp., Centipeda spp., and Campylobacter spp. Considering the vast microbial diversity in periodontitis, we aimed to analyze the presence of various bacterial species in subgingival dental plaque, with a special focus on Selenomonas spp. We first developed a phylogenetic tree for Selenomonas–Veillonella clusters, using in silico analysis followed by fluorescence in situ hybridization (FISH) on subgingival dental plaque samples from 22 patients with a history of chronic periodontitis, by using specific 16S rRNA oligonucleotide probes. These oligonucleotide probes’ specificity and hybridization conditions were determined on previously characterized bacterial strains. Qualitative and quantitative analysis of FISH slides was carried out by using an epifluorescence microscope. The majority of the patient samples showed high fluorescence signals with the oligonucleotide probes SEL1150, Sspu439, and SEL1469 (specific for Selenomonas spp.), ACI623 (identifying Selenomonas, Veillonella, and Dialister spp.), Tfor127 (T. forsythia) and L-Pgin1006-23 (P. gingivalis). SEL1150 showed specificity for bacterial species in the subclusters A, B, and C, namely S. dianae, S. infelix, S. flueggei, C. periodontii, S. artemidis, S. noxia, and S. sputigena; Sspu439 for S. sputigena; SEL1469 for subclusters A and B, and for S. sputigena; ACI623 for bacterial species in subclusters C and F, namely the S. sputigena and Veillonella species. The experimentally observed specificities of the oligonucleotide probes corresponded with our in silico analysis. Selenomonas spp. may play a role in the subgingival microbiome of periodontitis and contribute to the disease process. Targeting Selenomonas spp. with specific therapeutic strategies could offer new insights into the management of periodontitis. However, further studies are needed to determine a definite functional significance. Full article

Background and Clinical Significance: Parkinson’s disease (PD) is a neurodegenerative condition characterized by motor and non-motor symptoms, which significantly impact patients’ autonomy and quality of life levels. Basically, the PD diagnosis is clinical and, in some cases, can be challenging to diagnose due to the heterogeneity of the symptoms. Case Presentation: A 58-year-old woman who, during the COVID-19 lockdown, referred to experiences of slight tremor and stiffness in her left hand at rest, but without any other associated symptoms. Firstly, after consulting a general practitioner (GP), the patient was diagnosed with cervical radiculopathy (CR), presented as essential tremor and stiffness to the hand. Nevertheless, during the initial physiotherapy evaluation, the motor symptoms did not fully align with the diagnosis of CR. For this reason, the presence of non-motor symptoms was thoroughly investigated. Notably, hyperhidrosis was identified as a significant non-motor symptom, leading to the patient’s subsequent referral to a neurologist, who finally diagnosed PD. Conclusions: This case report highlights the essential role of physiotherapists in conducting independent assessments and comprehensive investigations of all patients’ symptoms, even when a medical diagnosis has already been established. This is particularly crucial when there is suspicion that musculoskeletal symptoms may be indicative of neurodegenerative diseases such as PD, which is well-known for its extensive array of non-motor symptoms. Especially in women with PD, non-motor symptoms tend to emerge earlier and in a more subtle manner than motor symptoms, making diagnosis challenging. Therefore, meticulous anamnestic data collection is essential, especially by physiotherapists working in direct-access settings. Full article

Background and Objectives: Diabetic retinopathy (DR) is a leading microvascular complication of type 2 diabetes (T2D). Fractalkine (CX3CL1), a chemokine involved in inflammation, angiogenesis, and microglial activation, may play a role in DR pathogenesis. This study investigated the association between serum fractalkine levels, the presence of DR, and disease severity. Materials and Methods: In this cross-sectional study, 140 adults with T2D were classified as non-DR (n = 32) or DR (n = 108) according to ICDR and ETDRS criteria; DR cases were further categorized into NPDR (n = 76) and PDR (n = 32), with NPDR staged as mild, moderate, or severe. Serum fractalkine concentrations were measured using ELISA. Results: Serum fractalkine levels were significantly higher in patients with DR than in those without retinopathy (0.7 vs. 0.4 ng/mL, p < 0.001). Within NPDR stages, fractalkine levels were highest in severe NPDR (p = 0.004). No significant fractalkine difference was found between NPDR and PDR groups. In multivariable analysis, serum fractalkine (OR 10.2; 95% CI 1.2–89.6; p = 0.036) remained independently associated with the presence of DR. For identifying DR, fractalkine yielded an AUC of 0.736; the optimal cut-off of 0.455 ng/mL provided 81.5% sensitivity and 56.3% specificity. In distinguishing severe NPDR, fractalkine demonstrated strong diagnostic performance (AUC = 0.784), with a cut-off of 0.720 ng/mL yielding 100% sensitivity and 61.9% specificity. Conclusions: Serum fractalkine is significantly associated with both the presence and severity of DR and remains independently associated with retinopathy after adjustment for traditional risk markers. Serum fractalkine may offer complementary systemic information in automated and AI-based retinal screening. These findings are exploratory and hypothesis-generating, and prospective studies are required to determine the clinical relevance of serum fractalkine in DR. Full article

Post-transcriptional regulation of gene expression is influenced by RNA-binding proteins (RBPs) and small non-coding RNAs that bind to conserved mRNA sequences to modulate mRNA processing. These regulatory molecules affect the structural conformation of mRNAs, creating formations like G-quadruplexes (G4s), which alter translation initiation and regulatory-factor site accessibility. Recent studies have highlighted Nuclear factor erythroid 2–related factor 2 (NRF2) as a key regulator of cellular redox homeostasis and cellular response to oxidative stress. An intriguing feature of NRF2 is the structural formation of its 5′ untranslated region (UTR), which may promote or inhibit translation initiation depending on the cellular context. In this study with minigenes, we provide in vitro evidence of RNA G4s in the NRF2 mRNA’s 5′ UTR under basal (no stress) conditions. Achieved via electrophoretic mobility shift assay and fluorescence spectra in the presence of Pyridostatin. Understanding how structural motifs within NRF2 5′ UTRs influence mRNA function provides insights into a common molecular mechanism underlying diseases where NRF2 is dysregulated, like cancers, cardiovascular disease, and neurodegeneration, and highlights potential therapeutic avenues through regulation of NRF2. Full article

Mycoplasma bovis (M. bovis) is a major pathogen responsible for bovine respiratory disease, mastitis, and arthritis, causing significant economic losses to the cattle industry worldwide. To elucidate the genetic and biological characteristics of M. bovis circulating in Yunnan Province, China, twenty PCR-positive bovine respiratory samples were collected from cattle farms in Kunming; three isolates—M.bo-YNXD-1, A1, and A8—were successfully cultured and identified through colony morphology, biochemical assays, and molecular characterization. Antimicrobial susceptibility testing showed that M.bo-YNXD-1 exhibited multidrug resistance to six antibiotics, including ciprofloxacin and lincomycin, while A1 and A8 were resistant to one or two agents, respectively. Multilocus sequence typing (MLST) analysis revealed that isolates M.bo-YNXD-1 and M.bo-YNXD-A8 belonged to sequence type ST52, whereas isolate M.bo-YNXD-A1 was assigned to ST90, indicating the coexistence of distinct genetic lineages in this region. Virulence gene screening showed that isolate M.bo-YNXD-A8 was positive for VspX and p81, whereas all three isolates were positive for p48 and Vpam. A SYBR Green I-based quantitative PCR (qPCR) assay targeting the oppD/F gene was established, exhibiting high specificity, a detection limit of 10 copies/μL, and intra-/inter-assay variation below 3%. Validation using clinical samples demonstrated superior sensitivity compared with conventional PCR. Taken together, these findings indicate the presence of distinct MLST genotypes and virulence-associated genetic heterogeneity among regional Mycoplasma bovis isolates, and introduce a rapid, sensitive, and reliable qPCR assay for early detection and epidemiological surveillance. This study provides critical insights for rational antimicrobial use and targeted control strategies against M. bovis infections. Full article

Background: Cardiometabolic risk is increasingly observed in young adults, particularly during university years, and is not limited to individuals with elevated body mass index. Emerging evidence highlights the presence of normal weight obesity—characterized by excess adiposity and unfavorable body composition despite normal BMI—which may confer early metabolic vulnerability. Dietary diversity is often promoted as a marker of dietary adequacy; however, its relationship with adiposity, body composition, and muscular health remains inconsistent, particularly in Latin American populations. Moreover, few studies have directly contrasted dietary diversity indicators with empirically derived dietary patterns in relation to cardiometabolic and functional outcomes. Objective: To examine the associations between dietary diversity, dietary patterns, and indicators of adiposity, muscular strength, and relative muscle mass in Ecuadorian university students. Methods: A cross-sectional study was conducted among 349 undergraduate students aged 18–26 years enrolled in health sciences programs in Ecuador. Dietary intake was assessed using a validated food frequency questionnaire. Dietary diversity was quantified using the Food and Agriculture Organization’s Individual Dietary Diversity Score, while dietary patterns were identified through principal component analysis followed by k-means clustering. Outcomes included excess body weight, relative muscle mass assessed by bioelectrical impedance analysis, and handgrip strength. Multivariable Poisson and linear regression models were fitted, adjusting for age, sex, academic program, physical activity level, and pre-existing conditions. Results: Despite their young age and low prevalence of diagnosed disease, approximately one-third of the participants exhibited markers of early cardiometabolic risk, including excess body weight and central adiposity. Higher dietary diversity was independently associated with a higher prevalence of excess body weight (adjusted prevalence ratio per one-unit increase in IDDS: 1.17; 95% CI: 1.06–1.30) and with greater relative muscle mass (adjusted β = 0.13; 95% CI: 0.05–0.22), whereas no association was observed with handgrip strength. In contrast, dietary patterns derived from multivariate analysis showed no significant associations with adiposity, muscular strength, or relative muscle mass after adjustment. Conclusions: In this young adult population, dietary diversity captured aspects of overall dietary exposure associated with both increased adiposity and greater lean mass, but not with muscular strength. Empirically derived dietary patterns demonstrated limited discriminatory capacity, likely reflecting dietary homogeneity within the cohort. These findings indicate that dietary diversity alone does not necessarily reflect diet quality and underscore the importance of interpreting diversity metrics alongside indicators of food quality, energy density, and body composition when evaluating early cardiometabolic risk in contemporary food environments. Full article

Background: Chronic heart failure (CHF) is a progressive cardiovascular disease that predominantly affects elderly individuals and significantly impairs quality of life. High mobility group box 1 (HMGB1) has been proposed as a key mediator in the myocardial release of proinflammatory cytokines and the progression of CHF. The primary aim of this retrospective study was to evaluate the clinical significance of plasma HMGB1 levels in patients with CHF. The secondary objective was to determine the prognostic and predictive value of plasma HMGB1. Methods: Prior to the commencement of the study, blood samples were collected from 145 patients diagnosed with CHF. Plasma HMGB1 concentrations were measured at a single baseline time point using the enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed to assess correlations between HMGB1 levels and cardiac, laboratory, and nutritional parameters. Results: Elevated HMGB1 levels were significantly associated with worse clinical status, including increased pulmonary artery systolic pressure (PASP, p = 0.011), enlarged right ventricular outflow tract (RVOT, p = 0.006), advanced New York Heart Association (NYHA) functional class III or IV (p < 0.001), and the presence of dyspnea at rest (p < 0.001). HMGB1 levels effectively distinguished between NYHA classes I–III and IV (AUC = 0.780), as well as between cachectic and non-cachectic individuals (AUC = 0.840). Importantly, higher plasma HMGB1 concentrations were significantly associated with shorter overall survival (OS) in CHF patients (HR = 2.03; p < 0.001). Conclusions: Plasma HMGB1 levels may suggest that they reflect both cardiac and nutritional status in patients with CHF and could serve as a valuable biomarker for disease severity and prognosis. Notably, elevated HMGB1 is strongly associated with reduced overall survival, supporting its potential use in risk stratification and clinical management of CHF. Full article

Background: Atrial fibrillation (AF) is frequently associated with cardiometabolic comorbidities, and increasing evidence suggests a close relationship between AF and liver disease, particularly metabolic dysfunction-associated steatotic liver disease (MASLD); however, the clinical patterns, hepatic phenotypes, and clinical implications of this association remain insufficiently characterized. Therefore, the aim of the present study was to characterize hepatic involvement in patients with paroxysmal AF by integrating a structured literature review with original clinical data. Methods: We performed a retrospective analysis of 253 patients admitted with paroxysmal AF between 2015 and 2025. Demographic data and associated diagnoses were collected with a specific focus on hepatic pathology. Patients were stratified according to the presence and type of liver disease, and descriptive statistics, bivariate analyses, and multivariate logistic regression were used to identify associations and independent predictors. Results: Liver disease was identified in 65.2% of patients, most commonly hepatic steatosis (46.2%), followed by liver cirrhosis or advanced liver disease (19.0%). Patients with liver disease had higher prevalences of type 2 diabetes mellitus, dyslipidemia, obesity, and alcohol consumption. Dyslipidemia (OR 4.51) and obesity (OR 2.54) were independent predictors of hepatic steatosis, whereas liver cirrhosis was inversely associated with age and serum lipid levels. Conclusions: Liver pathology is highly prevalent among patients with paroxysmal AF and is closely associated with adverse metabolic and clinical profiles. Recognition of distinct hepatic phenotypes may support improved risk stratification and multidisciplinary management in patients with AF. Full article