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Early prediction of colonization by carbapenemase-producing enterobacterales at ICU admission using machine learning
No full textAbstract Colonization by carbapenemase-producing Enterobacterales (CPE) on admission to an intensive care unit (ICU) poses a serious threat to infection control. Early detection is critical but remains challenging in real-world settings. We aimed to develop interpretable machine learning models for predicting CPE colonization at ICU admission to support clinical decision-making for early isolation of CPE carriers. We conducted a retrospective cohort study of adult ICU admissions at a tertiary hospital in South Korea from January 2022 to December 2023. CPE colonization was defined by rectal swab culture within 48 h of admission. Forty-two candidate variables were extracted from electronic medical records, and ten machine learning algorithms were evaluated. Of 4,915 ICU admissions, 453 (9.2%) were colonized with CPE at admission. Twelve predictors were retained for model development, including antibiotic exposure, device use, and medical condition. Logistic regression at a threshold of 0.45 achieved the best-balanced performance with a sensitivity of 0.73, an ROC-AUC of 0.77, and a negative predictive value of 0.96. A web-based CPE prediction tool was developed based on the model; this enables clinicians to enter the 14 selected variables at ICU admission and instantly obtain an estimated risk of CPE colonization. Our machine learning–based tool for predicting CPE colonization at ICU admission appears to hold promise as a rule-out aid for CPE carriage
Seasonal dynamics and core stability of the bacterial microbiome of a Drosophila suzukii wild population
No full textAbstract Drosophila suzukii (spotted-wing drosophila, SWD) is an invasive pest with pronounced sexual dimorphism and seasonal polyphenism. While seasonal morphotypes are well documented, how these phenotypic traits shape the SWD microbiome remains poorly understood. Here, we investigate how sex and seasonal phenotypes shape microbiome composition in SWD. We hypothesize that these factors drive microbial shifts, with some taxa varying between phenotypes and others forming a stable core. Understanding these patterns may reveal microbiome-associated adaptations relevant to SWD ecology and management. To investigate this, we monitored SWD microbiome dynamics over one year by collecting individuals during spring, summer, and autumn of 2022 and winter of 2023 from an organic farm in northern Portugal. Bacterial communities were compared using 16 S rRNA amplicon sequencing. This SWD population retained a core bacterial community, highly represented by Gluconobacter, Pseudomonas, Commensalibacter and Pantoea, consistent with other SWD Portuguese populations. Moreover, microbiome composition varied significantly across seasons but not between sexes, although females exhibited higher microbial alpha diversity. Linear discriminant analysis of relative abundance (LEfSe) revealed enrichment of Morganella, Methanosaeta, Serratia, Duganella, Frateuria, Suttonella, and Janthinobacterium in winter groups. However, functional prediction analyses revealed no significant differences in microbiome functional potential across seasons, suggesting functional redundancy despite taxonomic variation. This study offers baseline insights into the seasonal stability and plasticity of the D. suzukii microbiome, contributing to a deeper ecological understanding of this invasive pest
Real world outcomes of intravitreal and systemic therapy in primary and secondary vitreoretinal lymphoma
No full textAbstract Vitreoretinal large B-cell lymphoma (VR-LBCL) is a rare hematologic malignancy. It is classified as primary (PVR-LBCL) or secondary (SVR-LBCL) based on the initial site of manifestation. Owing to limited prospective data and absent standardized guidelines, treatment remains challenging. This dual-center retrospective study aimed to evaluate outcomes of methotrexate (MTX) intravitreal (itv.), Rituximab itv., or combinatorial itv. therapy (R-MTX) and assess the impact of additional systemic immunochemotherapy. Among 65 patients (median age 72 years) included, 55.4% (n = 36) had PVR-LBCL. The median time to diagnosis was 31 days (1–2805). Over a median follow-up of 23.2 months, 35 patients relapsed. MTX itv. showed a trend toward better ocular relapse-free-survival than Rituximab itv. (P = 0.07). Intriguingly, patients receiving R-MTX itv. experienced no relapses throughout follow-up. In general, addition of systemic therapy was associated with significantly longer relapse-free-survival compared to itv. monotherapy (P = 0.05). Keratopathy and elevated intraocular pressure were common side effects with MTX itv. and Rituximab itv., respectively. Despite compelling findings and being one of the largest cohorts published to date, the heterogeneity of the patient population and small subgroups limit direct clinical translation. Nonetheless, this study provides a strong foundation for the design of future clinical trials
Neurotransmitter alterations in seasonal affective disorder
No full textAbstract Seasonal affective disorder (SAD) is a type of unipolar depression characterized by depressive symptoms mainly during the cold season, which were often linked to alterations in the serotonergic system. It is assumed that other neurotransmitter systems, such as glutamate and GABA, are similarly affected. Hence, we investigated differences in glutamate and GABA between SAD patients and healthy control subjects using magnetic resonance spectroscopy imaging (MRSI). Fourteen SAD patients (11 female, 36 ± 11 years) and 14 sex- and age-matched healthy controls, were scanned once between October and February using multi-voxel 3D-GABA-edited MEGA-LASER MRSI at 3 T. Mean GABA+ and Glx (glutamate + glutamine) to total creatine (tCr) ratios were calculated in five brain regions. Mann–Whitney-U-Tests were performed for each region and neurotransmitter ratio independently as well as correlation analyses between neurotransmitter ratios and clinical scores, respectively. A significant reduction in GABA+/tCr ratios in the hippocampus (p corr = 0.049) between SAD patients and healthy individuals was revealed. No significant changes in other brain regions or correlations with the investigated clinical scores were shown. Our findings of altered GABA concentrations in the hippocampus are in line with neurotransmitter alterations across other subtypes of depression, hinting towards common neurobiological mechanisms and highlights the interplay between environmental factors and neurotransmitter systems
Square integrable solutions and stability of a second-order stochastic integro-differential equation
No full textAbstract This article investigates the stochastic asymptotic stability, boundedness, and square integrability of solutions to a class of second-order nonlinear stochastic integro-differential equations with multiple variable delays. The analysis is conducted through the construction of an appropriate Lyapunov–Krasovskii functional (L-KF), tailored to handle the combined effects of stochastic perturbations, time-varying delays, and integro-differential memory terms. Unlike many existing studies, our framework accommodates all these complexities simultaneously, thereby generalizing and extending recent contributions in the field while relaxing several restrictive assumptions. To validate the theoretical results and illustrate their practical applicability, numerical simulations are provided
3D heterotypic models of glioblastoma reveal the impact of microglia on cellular organization and the production of a distinct secretome
No full textAbstract Glioblastoma (GBM) is a deadly brain tumor with a very poor prognosis. Development of new therapeutics is hindered by the lack of appropriate preclinical models that reflect the complexity of the tumor microenvironment, especially the crucial role of microglia. In this study, we investigated the impact of microglia on GBM models using humanized 3D spheroids. Homotypic and heterotypic spheroids were created out of a GBM-derived cell line (DKMG) or patient-derived glioma stem cells (GB22-13), along with a microglia cell line (HMC3). Heterotypic glioma-HMC3 spheroids exhibited increased proliferation and greater drug resistance to chemotherapy drug Temozolomide compared with homotypic spheroids. Heterotypic spheroids also grew larger, developed multinucleated structures within 7 days, and had a greater invasive potential. Additionally, a distinct core-shell structure emerged in the heterotypic spheroids, with glioma cells concentrated in the core and a surrounding layer of microglia forming a protective shell that appeared to hinder drug penetration to the tumor core. Further, heterotypic cells were able to induce migration and polarization of peripheral blood monocytes (THP-1) towards M2 phenotypes, increasing immune evasion. These findings highlight the critical role of microglia in GBM development and progression, demonstrating their contribution to both reduced drug diffusion and increased tumor growth
Intelligent decision-making for mine ventilation systems based on graph neural network and deep reinforcement learning fusion
No full textAbstract Mine ventilation systems face significant challenges in dynamic control due to complex network topologies and uncertain underground environments. This paper proposes an intelligent decision-making framework that synergistically integrates graph neural networks (GNN) with deep reinforcement learning (DRL) for optimal ventilation control. A multi-level hierarchical graph representation method is developed to capture topological structures and spatial dependencies of ventilation networks, while an improved Actor-Critic algorithm with prioritized experience replay enables adaptive policy learning under safety constraints. The GNN encoder extracts graph-structured features that enhance the DRL agent’s state representation, facilitating efficient exploration and decision optimization. Experimental validation on simulation platforms and six-month field deployment in an operational coal mine demonstrate substantial improvements: 34.7% higher cumulative rewards compared to conventional methods, 23.7% reduction in energy consumption, and 98.4% safety compliance rate across diverse operational scenarios. The proposed framework advances intelligent mine ventilation management by simultaneously achieving enhanced safety assurance, improved energy efficiency, and robust adaptability to complex dynamic conditions
Prognostic value of the third thoracic vertebra skeletal muscle measurements in patients with digestive system malignancies: a comparative study with the third lumbar vertebra indices
No full textAbstract Skeletal muscle mass assessment using computed tomography (CT) is crucial for evaluating nutritional status and prognosis in cancer patients. While the third lumbar vertebra (L3) level is widely accepted for this purpose, not all patients undergo abdominal CT scans. This study aimed to explore the potential of the third thoracic vertebra (T3) level as an alternative measurement site. This retrospective study included 257 patients with digestive system malignancies. Skeletal muscle area (SMA) and skeletal muscle index (SMI) were measured at both T3 and L3 levels using CT scans. Correlation analyses, linear regression models, and cox regression analyses were performed to evaluate the relationship between T3 and L3 measurements and their prognostic value. Strong correlations were observed between T3 and L3 measurements (r = 0.833 for SMA, r = 0.747 for SMI). A multivariate linear regression model effectively predicted L3 SMA from T3 SMA (adjusted R² = 0.829). Cox regression analyses revealed that lower T3 SMA and SMI were independently associated with increased mortality risk. Patients in the lowest quartile of T3 SMA had significantly higher mortality risk compared to those in the highest quartile (HR = 5.82, 95% CI: 1.86–18.16, P = 0.002), after adjusting for confounders. Similar results were observed for T3 SMI and L3 measurements. T3 skeletal muscle measurements strongly correlate with L3 measurements and serve as independent prognostic factors in patients with digestive system malignancies. T3 measurements offer a viable alternative for assessing skeletal muscle mass and predicting prognosis when L3 measurements are unavailable
Validation of a fast LC-MS/MS method for the analysis of bisphenol A (BPA) and urethane dimethacrylate (UDMA) in eluates of dental polymer-based materials
No full textAbstract Polymer-based materials are widely used in dentistry. However, concerns exist regarding their biocompatibility because monomers such as urethane dimethacrylate (UDMA) and bisphenol A (BPA) may leach from the materials and affect the immune and endocrine systems. Since BPA and UDMA are biologically active even at low concentrations, validated and highly sensitive analytical methods are required. We developed a fast LC-MS/MS method enabling simultaneous detection of BPA and UDMA in artificial saliva using a short column and polarity switching. The method was validated for selectivity, specificity, carry-over, sensitivity, accuracy, precision, recovery, and matrix effects. A water–methanol gradient elution with post-column infusion of 6 mM NH₄F was used to enhance sensitivity. Lower limits of quantification (LLOQ) for UDMA and BPA were of 10pg/ml and 30pg/ml, respectively. The method was used to analyze eluates of thermoformed and 3D-printed polymer-based materials, which released very low amounts of BPA and UDMA. In eluates collected after 1 day, the thermoformed material released more BPA (154.6 ± 128.7 pg/mL) and UDMA (154.8 ± 24.0 pg/mL) than the 3D-printed resin (BPA: 30.7 ± 16.4 pg/mL, UDMA: under LLOQ). Despite the high sensitivity, all values were lower than LLOQ in eluates collected after 1 week. The method provides a fast and reliable tool for the simultaneous quantification of BPA and UDMA in the eluates of dental polymer-based materials, enabling a more accurate assessment of the safety of these materials
Stable isotope insights into water use sources and adaptation strategies of Tamarix Chinensis in desert ecotone of arid regions
No full textAbstract Water availability is a critical determinant of ecosystem stability and vegetation persistence in arid environments. Understanding the water-use strategies of xerophytic shrubs under diverse hydrological conditions is essential for elucidating plant-water interactions and informing ecological restoration practices. This study focuses on Tamarix chinensis communities across the desert-steppe ecotone in northwestern China. By analyzing the stable isotopic compositions of hydrogen and oxygen (δ²H and δ¹⁸O) in precipitation, soil water, xylem water, and groundwater, and applying a Bayesian mixing model (MixSIAR), this study quantitatively assessed the sources and controlling factors of water uptake under varying groundwater depths. The results reveal that Tamarix chinensis employs flexible water-use strategies that vary with habitat conditions. Rainfall contributed only (10% ± 2%) to total water uptake, while groundwater (24% ± 3%), mid-soil water (22% ± 3%), and deep-soil water (22% ± 3%) were the predominant sources. Under conditions of shallow groundwater and low salinity, the species accessed deep-soil water (27%) and groundwater (29%). As groundwater levels declined, reliance on groundwater decreased, and uptake shifted toward mid- (25%) and deep-soil layers (26%). Additionally, in areas with reduced vegetation richness, the contribution from shallow-soil water increased significantly, reaching 24.8%. These results demonstrate the strong ecological plasticity of Tamarix chinensis, which adjusts its water-use strategy in response to variation in groundwater depth, soil salinity, and community structure. The study provides critical insights for vegetation management and ecological restoration in arid and transitional desert regions
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