Search Results (28,280)

Background: Multidrug-resistant (MDR) Gram-negative bacilli (GNBs) significantly compromise the effective management of urinary tract infections (UTIs) worldwide. As antimicrobial resistance varies across regions, locally tailored data are essential to guide empirical therapy. This study investigated the prevalence, determinants, and temporal dynamics of MDR GNBs in UTI patients from Central Portugal between 2018 and 2022. Methods: We conducted a retrospective observational study at a hospital center in Central Portugal, analyzing data from 2018 to 2022. Data from 5194 UTI patients with GNB-positive cultures were analyzed. Binary logistic regression was used to identify determinants of MDR GNBs, defined as resistance to ≥1 agent in ≥3 antibiotic classes. Results: The study population had a mean age of 64.5 ± 25.3 years, and females represented two-thirds of the sample (67.0%). The overall prevalence of MDR GNBs was 35.8%. Advanced age (≥75 years), male sex, and specific treatment contexts—particularly day treatment and laboratory-only cases—were independently associated with MDR. SBL-producing Enterobacterales and non-fermenting GNBs showed the highest risk levels. Conclusions: MDR GNBs are highly prevalent among UTI patients in Central Portugal, and their increasing trend—particularly in 2022—highlights an urgent need for strengthened surveillance and updated empirical treatment strategies. The observed temporal increase highlights the urgent need for strengthened regional surveillance and updated empirical treatment guidelines. Full article

Background: The 1 min sit-to-stand test (1-MSTST) is a widely used functional assessment involving repetitive sit-to-stand transitions. This study examined local dynamic stability during the 1-MSTST across three acceleration directions, compared young and middle-aged women, and explored associations between body composition and stability. Methods: Twenty-four young adult women (24.1 ± 5.2 years) and twenty-four middle-aged women (51.4 ± 5.9 years) performed the 1-MSTST. Trunk accelerations were recorded using a tri-axial accelerometer at L5. Local dynamic stability was quantified using the largest Lyapunov exponent (LyE), and movement magnitude using root mean square (RMS). Directional, group, and correlational analyses were performed with correction for multiple testing. Results: Significant directional differences were observed for both LyE and RMS, with all pairwise contrasts between mediolateral (ML), anteroposterior (AP), and vertical (VT) directions remaining significant after correction (p < 0.001). Apparent age effects in LyE were no longer significant after adjusting for cadence, BMI, and multiple testing, indicating no robust age-related difference in local dynamic stability. Body fat percentage showed moderate positive correlations with LyE in the VT (p = 0.003) and AP (p = 0.003) directions. Muscle mass percentage showed a moderate positive correlation with VT LyE (p = 0.002) and moderate negative correlations with ML (p = 0.002) and AP LyE (p = 0.002). Conclusions: Stability during the 1-MSTST differs by direction, with the greatest variability in the mediolateral axis. No independent age effect was found. Higher body fat relates to poorer stability, while greater muscle mass supports better movement control. Full article

In recent decades, the rate of kidney transplantation has risen significantly, leading to better outcomes in terms of cardiovascular and overall mortality for patients with kidney failure. Although kidney transplantation represents the most effective therapeutic option, it is not devoid of the risk of failure. Immunological and non-immunological risk factors are involved. These factors often interact and may act synergistically, ultimately influencing graft longevity and patient survival. Both contribute to long-term transplant outcomes; however, non-immunological factors, representing a significant clinical challenge, will be the focus of our review. Of the numerous non-immunological risk factors, for clarity and to avoid overextending the discussion, only those most closely associated with chronic kidney disease have been considered: hypertension, anemia, diabetes mellitus, proteinuria, electrolyte and acid–base imbalances, and impaired bone mineralization. Hypertension is reported in approximately 90% of kidney transplant recipients, often related to immunosuppressive therapy and residual renal dysfunction, and it is strongly associated with reduced graft survival. Anemia affects approximately 20–51% of these patients, contributing to cardiovascular morbidity and a more rapid decline in graft function, as does pre-existing diabetes mellitus. Proteinuria has a prevalence ranging from 7.5% to 45%, depending on the established target, and is a significant negative prognostic factor. Metabolic complications are also frequent; for example, hyperkalemia has an incidence of 25–44%, and metabolic acidosis has a prevalence of 12–58%. In our review, each of these factors is analyzed in terms of clinical impact, etiopathogenic mechanism, and available therapeutic management. Full article

Background/Objectives: Current data-driven dietary pattern methods have limitations in identifying disease-specific dietary structures. We developed network-derived dietary scores based on type 2 diabetes (T2D)-differential food co-consumption networks and examined their associations with incident T2D risk. Methods: Using the Korean Genome and Epidemiology Study-CArdioVascular disease Association Study (KoGES-CAVAS, n = 16,665), we constructed food co-consumption networks from cumulative average intakes stratified by incident T2D status. The network centrality scores from edges appearing exclusively in either T2D or non-T2D networks were used to generate a differential co-consumption network-derived (D_CCN) score, with higher scores indicating a greater alignment with diabetes-specific structures. CAVAS-derived scores were applied to the Health Examinee Study (KoGES-HEXA, n = 51,206) for cross-cohort validation. Incidence rate ratios (IRRs) were estimated using modified Poisson regression with robust error estimation. Results: During follow-up, 953 and 2190 new cases of T2D were identified in CAVAS and HEXA, respectively. Rice and vegetable dishes were primary hub foods in both networks, with rice showing exclusively negative correlations. Non-T2D networks were more complex, whereas T2D networks were simpler and centered on refined flour-based foods. The D_CCN score was associated with a higher T2D risk in CAVAS (IRR = 1.45, 95% CI: 1.21–1.74), and this association was validated in HEXA (IRR = 1.58, 95% CI: 1.40–1.78), with consistent dose–response relationships (both p-trend < 0.0001). Conclusions: Differential network analysis identified T2D-specific co-consumption structures, and the D_CCN score consistently predicted T2D risk across cohorts. This approach highlights the utility of network-based methods for capturing disease-relevant dietary structures beyond traditional approaches. Full article

Musculoskeletal pain is a common complaint during pregnancy and can persist into the postpartum period, negatively impacting maternal quality of life. While physical activity has demonstrated preventive benefits in various clinical settings, its specific role in the evolution of perinatal musculoskeletal pain remains unclear. The aim of this study was to examine whether daily time spent exercising moderates the trajectory of musculoskeletal pain from pregnancy to the postpartum period, considering pain experienced during the first 48 h after delivery as a potential mediating variable. Methods: A longitudinal study was conducted with a sample of 117 women assessed at three time points: during the third trimester of pregnancy, 48 h postpartum, and three months postpartum. A model of moderate mediation was tested using PROCESS Macro (Model 7) for SPSS. Pain in the third trimester was specified as a predictor (X), pain at 48 h postpartum as a mediator (M), pain at three months postpartum as an outcome (Y), and exercise during pregnancy as a moderator (W) of the relationship between X and M. Results: pain in the third trimester significantly predicted pain at three months postpartum (p < 0.001), and this relationship was partially mediated by pain at 48 h postpartum. Physical exercise significantly moderated this pathway (p = 0.0057), and higher levels of exercise were associated with less association across time over time. The moderate mediation index was significant (95% CI [0.0093, 0.1095]), highlighting physical activity as a relevant protective factor against persistent postpartum pain. Full article

Body composition, bone mineral density, and cardiopulmonary exercise testing (CPET) are commonly used to assess aerobic fitness in athletes, but their interrelationships remain unclear. This study compared these parameters by sex and examined their associations in elite athletes. Our study included 145 youth water polo players (age: 15.7 ± 1.6 years; male: 75). Body composition was measured by DEXA, and treadmill CPET was performed using a sport-specific protocol. We analysed the correlations between the following factors by multivariate linear regression: lean body mass (LBM, LBM_index); body fat mass (BFM); percent body fat (PBF); bone mineral content (BMC); lumbar, femoral, and radial bone mineral density (LBMD, FNBMD, FTBMD, RBMD); exercise time; absolute and relative maximal oxygen uptake (VO_2absmax, VO_2relmax); maximal ventilation (VE_max). Exercise time was found to be negatively correlated with BFM, while VO_2relmax was found to be negatively correlated with BFM and PBF. VO_2absmax was found to be positively correlated with BFM, LBM, BMC, FNBMD, and RBMD. VE_max was found to be positively correlated with LBM and LBM_index. In males, VO_2absmax and VE_max were found to be positively correlated with LBMD and FTBMD. Correlations between bone density and CPET proved to be stronger in males. Our results indicate that body composition and bone density parameters influence CPET parameters, and their complex evaluation can support personalized diagnostics and athletes’ health. Full article

Human epidermal growth factor receptor 2 (HER2)-low breast cancer is a clinically relevant subgroup defined by low but detectable HER2 protein expression, immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization findings, positioned at the interface between traditional HER2-positive and HER2-negative disease. The recent introduction of antibody–drug conjugates (ADCs) has increased the clinical significance of borderline HER2 expression and exposed important diagnostic challenges, particularly in cases with very low levels of membrane staining, including the emerging HER2-ultralow category. Background and Objectives: This review summarizes the pathological and biological framework of HER2-low and HER2-ultralow breast cancer and critically appraises the magnitude, direction, and determinants of HER2 variability under systemic therapy. Particular focus is placed on treatment-associated shifts after chemotherapy, intratumoral heterogeneity, and pre-analytical and analytical factors that can influence HER2 assessment, with direct implications for therapeutic stratification and biomarker reassessment. Materials and Methods: A narrative literature review was conducted using PubMed, Scopus, and Web of Science, focusing on studies published within the last five years. Eligible publications included clinical trials, retrospective cohorts, and translational or molecular studies that reported paired HER2 assessment in breast cancer and were interpreted according to American Society of Clinical Oncology/College of American Pathologists-aligned criteria. Results: Across major cohorts, HER2-low appeared to be the most dynamic category, with variability frequently observed following systemic therapy. Beyond treatment-related effects, shifts in HER2 status may be attributable to intratumoral heterogeneity and technical variability, with the greatest impact observed at the IHC 0–1+ interface. Conclusions: Given the clinical relevance of low-level HER2 expression, standardized testing and transparent reporting are essential, and HER2 reassessment may be justified in selected clinical scenarios to optimize access to HER2-directed therapies. Full article

Reaction time (RT) is a key indicator of cognitive and motor processing speed, and its age-related decline has important implications for everyday activities such as driving. However, conventional Psychomotor Vigilance Tests (PVTs) assess hand responses and do not capture lower-limb reaction characteristics relevant to pedal operations. This study aimed to compare RT characteristics between younger and older adults using the foot-response version of the PVT (Foot PVT) and to examine factors associated with RT. Sleep-related variables, physical activity level (PAL), and height were analyzed, and RT distribution characteristics were evaluated. Twenty younger adults (24 ± 3 years, range: 22–29 years) and twenty-four older adults (73 ± 5 years, range: 66–84 years) performed a 10 min Foot PVT. Mean RT was significantly slower in older adults (818 ± 105 ms) than in younger adults (700 ± 73 ms) (p < 0.001), indicating an age-related delay of approximately 120 ms. Older adults showed lower skewness and kurtosis, suggesting more homogeneous and cautious responses. In younger adults, height was negatively correlated with RT (r = −0.593, p = 0.006), and multiple regression analysis identified height as a significant predictor (adjusted R² = 0.316). No significant predictors were found in older adults. In the combined sample, age and height jointly explained 37.2% of the variance in mean RT. These findings indicate that Foot PVT performance reflects both biomechanical characteristics and age-related declines in reaction speed, supporting its utility for assessing lower-limb reaction capabilities relevant to driving and aging. Full article

Neutral atomic hydrogen (H I) regulates galaxy growth and quenching, but direct 21 cm measurements remain observationally expensive and affected by selection biases. We develop Bayesian neural networks (BNNs)—a type of neural model that returns both a prediction and an associated uncertainty—to infer the H I mass, ${log}_{10}\left(M_{\mathrm{HI}}\right)$, from widely available optical properties (e.g., stellar mass, apparent magnitudes, and diagnostic colors) and simple structural parameters. For continuity with the photometric gas fraction (PGF) literature, we also report the gas-to-stellar-mass ratio, ${log}_{10}(G/S)$, where explicitly noted. Our dataset is a reproducible cross-match of SDSS DR12, the MPA–JHU value-added catalogs, and the 100% ALFALFA release, resulting in 31,501 galaxies after quality controls. To ensure fair evaluation, we adopt fixed train/validation/test partitions and an additional sky-holdout region to probe domain shift, i.e., how well the model extrapolates to sky regions that were not used for training. We also audit features to avoid information leakage and benchmark the BNNs against deterministic models, including a feed-forward neural network baseline and gradient-boosted trees (GBTs, a standard tree-based ensemble method in machine learning). Performance is assessed using mean absolute error (MAE), root-mean-square error (RMSE), and probabilistic diagnostics such as the negative log-likelihood (NLL, a loss that rewards models that assign high probability to the observed H I masses), reliability diagrams (plots comparing predicted probabilities to observed frequencies), and empirical 68%/95% coverage. The Bayesian models achieve point accuracy comparable to the deterministic baselines while additionally providing calibrated prediction intervals that adapt to stellar mass, surface density, and color. This enables galaxy-by-galaxy uncertainty estimation and prioritization for 21 cm follow-up that explicitly accounts for predicted uncertainties (“risk-aware” target selection). Overall, the results demonstrate that uncertainty-aware machine-learning methods offer a scalable and reproducible route to inferring galactic H I content from widely available optical data. Full article

The exceptional olfactory capabilities of trained detection dogs demonstrate high potential for identifying infectious diseases. However, safe and standardized canine training requires specific chemical targets rather than infectious biological samples. This study presents an analytical proof-of-concept combining untargeted metabolomics and machine learning (ML) to decode the specific odor profile of SARS-CoV-2 infection. Using headspace solid-phase microextraction gas chromatography coupled with time-of-flight mass spectrometry (HS-SPME-GC/MS-ToF), axillary sweat samples from 76 individuals (SARS-CoV-2 positive and negative) were analyzed. Data preprocessing and dimensionality reduction were performed to feed a Partial Least Squares-Discriminant Analysis (PLS-DA) model. The optimized model achieved an overall accuracy of 79%, with a specificity of 89% and sensitivity of 70% in external validation, identifying a specific panel of Volatile Organic Compounds (VOCs) as discriminant biomarkers. The optimized model achieved robust classification performance, effectively distinguishing infected individuals from healthy controls based solely on their volatilome. Six VOCs were found to be consistently presented in COVID-19-positive individuals. These compounds were proposed as candidate odor signatures for constructing artificial training aids to standardize and accelerate the training of detection dogs. This study establishes a framework where machine learning-driven metabolomic profiling directly informs biological sensor training, offering a novel synergy between ML and biological intelligence in disease detection. This study establishes a scalable computational framework to translate biological samples into chemical data, providing the scientific basis for designing safe, synthetic K9 training aids for future infectious disease outbreaks without the biosafety risks associated with handling live pathogens. Full article

Background: Porphyromonas gingivalis outer membrane vesicles (OMVs) are key mediators of host–pathogen interactions and have been implicated in both periodontal disease and systemic conditions, including pregnancy complications. Although OMV production and cargo are known to be influenced by environmental stress, how oxidative stress reshapes P. gingivalis OMVs and their functional impact on trophoblast cells remains poorly understood. Here, we investigated how exposure to hydrogen peroxide (H₂O₂) affects OMV biogenesis, composition, and their ability to modulate bacterial invasion in trophoblast cells. Methods: P. gingivalis was cultured anaerobically and exposed to 30 mM H₂O₂ during the final 24 h of growth. OMVs were isolated by differential ultracentrifugation and characterized by nanoparticle tracking analysis and transmission electron microscopy and OMV protein cargo was analyzed by proteomics. Functional effects were assessed using invasion and persistence assays in HTR-8/SVneo trophoblast cells pretreated with OMVs. Results: Oxidative stress did not significantly alter total OMV yield but resulted in smaller vesicles (control OMV 168.2 ± 8.7 nm vs. OMV from H₂O₂-treated cultures 130.0 ± 13.8 nm) with reduced negative surface charge and increased membrane-associated FM4-64 fluorescence. Proteomic analysis revealed a remodeling of the OMV protein cargo under oxidative stress, including the selective enrichment of a von Willebrand factor type A domain-containing protein. Functionally, OMVs from control cultures led to a 2.5-fold increase in P. gingivalis invasion and a 4-fold increase in intracellular persistence in trophoblast cells, whereas OMVs produced under oxidative stress failed to promote these processes. Conclusions: Together, these findings highlight oxidative stress as a key determinant of OMV-mediated host–pathogen interactions at the maternal–fetal interface. Full article

Background: Evidence on long-term visual field progression in childhood glaucoma compared with open-angle glaucoma (OAG) is limited. We compared the rate and timing of visual field progression and identified predictors of final visual field status. Methods: Single-center, retrospective, observational study including childhood glaucoma and OAG, with ≥3 reliable visual field tests and ≥2 years of follow-up. Visual fields were obtained with Octopus perimeter (Haag-Streit Diagnostics, Köniz, Switzerland) with the G grid and TOP strategy. Visual field progression was evaluated using the rate of change in mean defect (MD, dB/year). Rates were compared with the Mann–Whitney U test. Timing was evaluated with Kaplan–Meier and restricted mean survival time (RMST). Cox models assessed risk of progression. Secondary analysis used multiple linear regression to identify predictors of final MD. The mean follow-up duration was 5.7 ± 2.6 years. Results: 171 eyes (87 childhood glaucoma, 84 OAG) were analyzed. Childhood glaucoma had worse baseline MD (10.7 ± 7.5 dB) than OAG (5.1 ± 6.5 dB, p < 0.001), and underwent more surgeries, while OAG used more medications. The median MD progression rate was −2.3 dB/year [IQR: −5.6 to 0.1] in childhood glaucoma vs. 0.0 dB/year [IQR: −1.2 to 1.3] in OAG (p < 0.001), a value consistent with functional stability under treatment, with some eyes showing negative slopes indicating relative improvement. In Octopus perimetry, MD is expressed on a positive scale, so a negative slope reflects absence of visual field worsening, suggesting comparatively greater deterioration in OAG. Kaplan–Meier curves showed similar progression-free survival between groups (Log-Rank p = 0.284). RMST at 12 years was 10.93 years in childhood glaucoma and 10.56 years in OAG (difference ≈ 4.4 months, not clinically relevant). These survival results should be interpreted cautiously due to the low number of progression events and the high censoring rate. In regression, baseline MD was the strongest predictor of final MD; a higher number of medications was associated with worse final MD; number of surgeries and follow-up duration were not significant predictors. Conclusions: MD slopes suggested faster deterioration in OAG than in childhood glaucoma, whereas the timing to first progression was similar between groups. Baseline differences and treatment patterns were consistent with functional stability in childhood glaucoma under current management strategies. These findings support individualized follow-up and timely intervention, especially in pediatric patients. Full article

Background: Sentinel lymph node (SLN) biopsy has emerged as a cornerstone in melanoma staging, offering targeted evaluation of regional lymphatic spread and guiding therapeutic decision-making. Traditionally, SLN mapping relies on lymphoscintigraphy using technetium-99m (Tc-99m) radiocolloid, but in recent years, indocyanine green (ICG) fluorescence imaging has emerged as a promising alternative. The aim of this review is to evaluate the diagnostic accuracy of ICG–near-infrared (NIR) imaging compared to standard Tc-99m lymphoscintigraphy in SLN biopsy (SLNB). Methods: A systematic review and meta-analysis were conducted, including 12 studies. The primary outcome was the false-negative rate; secondary outcomes included the total number of sentinel lymph nodes (SLNs) identified by ICG–NIR imaging and Tc-99m lymphoscintigraphy, the number of metastatic SLNs detected by each method, and the number of patients with metastatic disease. The statistical analysis for dichotomous variables was performed using the “Odds Ratio” (O.R.) calculated with the Mantel–Haenszel method. For continuous variables, the analysis utilized the “Mean Difference” calculated by the inverse variance method. All data are presented with a 95% confidence interval (CI). Results: ICG was associated with a significantly higher number of SLNs identified compared to Tc-99m (O.R.: 0.41, 95% CI: 0.34–0.49; p < 0.00001), while no significant differences were found in the detection of metastatic nodes, either as a proportion of total SLNs (O.R.: 1.04, 95% CI: 0.86–1.25; p = 0.68) or relative to total positive nodes (O.R.: 0.36, 95% CI: 0.16–0.81; p = 0.01). No statistically significant differences between the two techniques were found in the detection of metastatic patients (OR: 0.80, 95% CI: 0.31–2.03, p = 0.33) and in the total number of false-negative patients missed (risk difference (RD): 0.03, 95% CI: −0.04 to 0.09, p = 0.93). Conclusions: While ICG identifies a higher number of SLNs compared to Tc-99m, its ability to detect metastatic involvement is comparable between the two modalities. No significant differences were observed in the proportion of metastatic SLNs, the total number of positive nodes detected, the number of metastatic patients identified, and the false-negative rate. Given its favorable profile, ICG could represent a reliable alternative or adjunct to Tc-99 in SLNB. However, prospective studies are warranted to validate its standalone diagnostic role. Full article

Heart rate variability (HRV) reflects autonomic nervous system (ANS) activity and provides insight into physiological and emotional regulation. Evaluating HRV during postural and emotional challenges may help characterize autonomic adaptability in healthy individuals. HRV was recorded in 24 young medical residents (17 females, 7 males; mean age 27.04 ± 1.97 years) during four conditions: rest, orthostatic standing, and exposure to positive and negative emotional images. Each session lasted five minutes. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Heart rate increased significantly only during standing, consistent with sympathetic activation with postural change. Spectral and normalized HRV parameters (nLF, nlf, LF/HF, and normalized coherence) were lowest at rest and increased during standing and emotional image exposure, particularly in males. Parasympathetic indices showed opposite trends. Emotional image exposure did not produce significant differences between positive and negative valence at the group level; however, sex- and anxiety-related patterns emerged. Females with anxiety showed increased heart rate during positive image exposure, whereas non-anxious females exhibited higher heart rate responses to negative images. Orthostatic challenge elicited the strongest autonomic response, whereas emotional visual stimuli induced subtler, sex- and anxiety-dependent autonomic modulation without overall changes in heart rate. These preliminary observations suggest that anxiety and sex may be associated with differences in cardiac autonomic regulation in young healthy adults. These results should be interpreted cautiously, given the pilot design, the small sample size (N = 24), the imbalance between sexes, the exclusion of the depression subgroup from inferential analyses, and the use of non-validated emotional visual stimuli Full article

Primary effusion-based lymphomas are uncommon and may pose significant diagnostic challenges. Fluid overload-associated large B-cell lymphoma is a recently recognized entity in the 5th edition of the World Health Organization Classification of Hematolymphoid Tumors and should be included in the differential diagnosis of effusion-based lymphomas, particularly in elderly immunocompetent patients with conditions that predispose to fluid overload. Background and Clinical Significance: We report a case of fluid overload-associated large B-cell lymphoma to add to the limited literature and highlight distinguishing features from other primary effusion lymphomas. Case Presentation: A 77-year-old male with end-stage renal disease on hemodialysis and heart failure with reduced ejection fraction was admitted for respiratory failure and found to have a right-sided pleural effusion. Two pleural fluid specimens examined several weeks apart revealed sheets of large atypical lymphoid cells positive for CD20, Pax-5, CD79a, CD45, MUM1, BCL2, BCL6 (weak) and negative for TTF1, CD68, MOC31, BER EP4, WT1, Calretinin, CD3, CD138, CD30, and cMYC. Human Herpesvirus-8 and Epstein–Barr virus were negative. Staging showed a few mildly fluorodeoxyglucose-avid mediastinal lymph nodes which were benign. Ultimately, the patient was diagnosed with fluid overload-associated large B-cell lymphoma and treated with rituximab, cyclophosphamide, vincristine sulfate, and prednisone, but passed away three months after diagnosis. Conclusions: Fluid overload-associated large B-cell lymphoma is a new and important diagnostic consideration in effusion-based lymphomas. It may be mistaken for other conditions such as primary effusion lymphoma or other diffuse large B-cell lymphomas. The presence of a Human Herpesvirus-8-negative effusion-based lymphoma in an elderly immunocompetent patient without nodal or tissue involvement should prompt consideration of fluid overload-associated large B-cell lymphoma. Full article