Search Results (4,369)

Human space exploration exposes astronauts to environmental stressors including microgravity (µg) and ionizing radiation, which may adversely affect cardiovascular health. Human induced pluripotent stem cell (hiPSC)-derived cardiac organoids, also referred to as cardioids, provide a physiologically relevant model to investigate these effects, but preservation of complex 3D tissues remains challenging. Current methods rely mainly on cryopreservation, creating variability and logistical constraints, particularly for spaceflight research. Alternative preservation strategies suitable for both ground-based and space experiments are therefore needed. In this study, human cardiac organoids were exposed to simulated µg (sµg) using a random positioning machine (RPM) and to a mixed neutron–photon field generated by a Californium-252 (²⁵²Cf) source. To assess preservation potential, organoids preserved at ambient temperature in CellShip^® transport medium were compared with unpreserved controls. Viability, proliferative activity and functional performance, including spontaneous beating, were assessed. Simulated µg induced limited detectable effects, whereas chronic irradiation (dose equivalent rate, 1.31–1.33 mSv/h over 70.5–74.7 h) impaired several organoid viability and functional readouts. Ambient-temperature-preserved organoids showed greater recovery of measurable beating after irradiation than unpreserved organoids. These proof-of-concept findings support further evaluation of CellShip^®-based ambient preservation as a non-cryogenic alternative for cardiac organoids in terrestrial and spaceflight research. Full article

Major depressive disorder (MDD) is associated with immune dysregulation, but the contribution of chemotaxis-related genes remains incompletely understood. This study aimed to identify chemotaxis-related signatures in MDD and evaluate their diagnostic relevance. Two peripheral-blood microarray datasets (GSE76826 and GSE38206) were integrated after batch correction, and differentially expressed genes were intersected with the GOBP_TAXIS gene set. Hub genes were selected using random forest and SVM-RFE and evaluated by logistic regression, ROC, calibration, and decision curve analyses. Immune-cell abundance, molecular subtypes, single-nucleus expression, and in silico gene-knockout effects were further examined, followed by qRT-PCR and Western blot validation in a CUMS rat model. The integrated cohort included 21 controls and 29 MDD cases. GOBP_TAXIS activity was increased in MDD (p < 0.001), and seven candidate genes yielded three upregulated hub genes (CXCL2, NRG1, and C3AR1). The fixed three-gene model yielded an exploratory AUC of 0.889 in the development cohort. All three genes correlated positively with monocytes/neutrophils and negatively with T cells. Single-cell analysis revealed cell-specific enrichment, while in silico knockout simulations predicted transcriptional changes involving RORB and NTNG1 following virtual perturbation of CXCL2 and NRG1. Animal experiments confirmed consistent upregulation at both transcriptional and translational levels. CXCL2, NRG1, and C3AR1 represent candidate chemotaxis-related biomarkers for MDD and are associated with distinct immune-cell abundance patterns and inflammatory signatures, warranting further functional validation. Full article

Generative AI-enabled teaching increasingly requires evaluation mechanisms that can process large candidate indicator sets without being dominated by uneven category frequencies or redundant variables. Existing filter methods are computationally inexpensive but mainly measure marginal relevance, whereas wrapper optimizers can capture feature interactions at the cost of a rapidly expanding combinatorial search space. Standard PSO can additionally be sensitive to random initialization and fixed or weakly adaptive search controls, which may reduce diversity or promote premature convergence. To address this computational trade-off, this study combines a conditional generative adversarial network (CGAN) for class-conditioned rebalancing, a two-stage Pearson correlation coefficient and improved particle swarm optimization (PCC–IPSO) procedure for indicator/feature selection, and a parallel-pooling one-dimensional convolutional neural network with a bidirectional gated recurrent unit (1D-CNN–BiGRU) for downstream validation. IPSO uses Logistic–Sine chaotic initialization, nonlinear inertia control, asymmetric cognitive/social learning-factor schedules, and adaptive t-distribution mutation. Because no classroom dataset is introduced, the computational mechanism is examined on the five-class NSL-KDD benchmark as a high-dimensional, strongly imbalanced test bed. PCC reduces the 41 benchmark variables to 31, and the archived IPSO output contains 16 selected variables. The retained experimental record reports 99.06% aggregate accuracy for the integrated benchmark pipeline and favorable single-run convergence behavior on several optimization functions. However, the archived record does not preserve an independently verifiable final split identifier, repeated-seed statistics, synthetic-sample distance metrics, or computational-cost measurements; therefore these results are reported as recorded benchmark outcomes rather than as statistically validated superiority or official-KDDTest+ performance. Within these limits, the study illustrates how generative rebalancing and deliberately asymmetric heuristic search can be combined for reduced indicator selection under distribution asymmetry. Full article

Objective: This study evaluated the association between admission Naples Prognostic Score (NPS) and in-hospital mortality in patients with clinical features consistent with type 2 cardiorenal syndrome (CRS-2). Methods: This retrospective, single-center study included 101 adults hospitalized for decompensated heart failure at Sakarya University Training and Research Hospital between June 2021 and August 2024. CRS-2 classification relied on nephrologist review of historical records. Admission NPS combined albumin, total cholesterol, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. NPS was analyzed primarily as a continuous score using univariable and multivariable Firth penalized logistic regression with profile penalized-likelihood confidence intervals. Low (0–2) versus high (3–4) NPS comparisons were exploratory; no patient scored 0. Results: Overall, 26 patients (25.7%) died. Mortality was higher in the high-NPS than the low-NPS group (24/52 [46.2%] versus 2/49 [4.1%]; p < 0.001). After adjustment for age, New York Heart Association (NYHA) functional class, and left ventricular ejection fraction (LVEF), the odds ratio per one-point NPS increase was 3.42 (95% confidence interval [CI], 1.76–7.77; p < 0.001). The area under the receiver operating characteristic curve was 0.825 (percentile bootstrap 95% CI, 0.744–0.896). At the established NPS ≥ 3 category boundary, sensitivity was 92.3% (95% CI, 75.9–97.9%) and specificity was 62.7% (95% CI, 51.4–72.7%). Performance was estimated within the same cohort without optimism correction or external validation. Conclusions: Higher admission NPS was associated with in-hospital mortality after adjustment for age, NYHA class, and LVEF. These exploratory findings require external validation and assessment of incremental predictive value and clinical utility. Full article

Cognitive dysfunction is increasingly recognized as a significant complication of chronic kidney disease (CKD), but the clinical relevance of protein-bound uremic toxins (PBUTs) to cognition remains insufficiently characterized. This cross-sectional analysis included 1217 community-dwelling individuals. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with scores < 28 indicating possible mild cognitive impairment (MCI). Serum concentrations of five PBUTs—indoxyl sulfate, p-cresyl sulfate, phenyl sulfate, indoleacetic acid, and hippuric acid—were measured, and a composite PBUT score was derived using principal component analysis. Multivariable logistic regression was used to examine the associations of MCI with the PBUT score and with each PBUT. Serum PBUT concentrations increased with advancing CKD stage. The mean MMSE score was 26.7 ± 3.4, and scores progressively declined with advancing CKD stage. A higher PBUT score was independently associated with MCI (coefficient, 0.290 ± 0.077; odds ratio, 1.337; 95% confidence interval, 1.151–1.554; p < 0.001). In conclusion, a greater PBUT burden was independently associated with cognitive impairment. These findings identify PBUT burden as a potential correlate of cognitive impairment in CKD. Prospective studies are needed to clarify its temporal relationship with cognitive decline and to assess whether it provides predictive value beyond established measures of kidney function. Full article

Background: Brain metastases are the most common malignant intracranial tumors and remain associated with poor survival despite advances in multimodal treatment. This study aimed to evaluate the associations between clinical, radiological, surgical, and perioperative characteristics and outcomes in patients undergoing surgical resection of brain metastases. Materials and Methods: This retrospective single-center cohort study included 378 consecutive adult patients who underwent resection of histopathologically confirmed brain metastases between 2015 and 2023. Overall survival was estimated using the Kaplan–Meier method, and differences between groups were assessed using the log-rank test. Factors associated with overall survival were evaluated using univariable and multivariable Cox proportional hazards regression. Binary logistic regression was used to evaluate factors associated with 30-day mortality. Results: Median overall survival was 11.3 months, the one-year survival rate was 45.5%, and 18 patients (4.8%) died within 30 days after surgery. In the adjusted logistic regression model, preoperative KPS < 80, hydrocephalus, postoperative hematoma, and postoperative pneumonia were associated with higher odds of 30-day mortality. In the multivariable Cox regression analysis, increasing age, preoperative KPS < 80, tumor volume ≥ 9 cm³, hydrocephalus, wound complications, and postoperative KPS deterioration were independently associated with shorter overall survival. Subtotal versus total resection was not significantly associated with overall survival after adjustment. Conclusions: Several preoperative and postoperative characteristics were associated with early mortality and overall survival in this surgically selected cohort. These findings emphasize the importance of careful patient selection, preservation of functional status, optimization of perioperative care, and prevention of postoperative complications. Full article

Background: Osimertinib is the standard of care for epidermal growth factor receptor mutation-positive non-small cell lung cancer, but heart failure hospitalization (HFH) remains a concern, and no practical tool exists to stratify HFH risk during therapy. Methods: In this retrospective cohort study using a Japanese claims database, 5802 patients newly initiating osimertinib were followed for HFH during treatment. Baseline predictors assessed before the index date were selected by 10-fold cross-validated least absolute shrinkage and selection operator (LASSO) logistic regression and internally validated by bootstrapping (B = 500), repeating predictor selection in each resample. Cumulative incidence functions and Fine–Gray models treated death as a competing event; cause-specific Cox models served as sensitivity analyses. Results: HFH occurred in 169 patients (2.9%) during a median on-treatment follow-up of 9.3 months, with 268 competing deaths. LASSO retained seven predictors. The apparent concordance index (C-index) was 0.731 (95% confidence interval, 0.691–0.771) and the optimism-corrected C-index 0.718. Observed incidence increased 10.2-fold across predicted-risk deciles (1.03–10.50%). Fine–Gray and Cox estimates closely matched the logistic model. Conclusions: Baseline cardiovascular vulnerability stratifies HFH risk during osimertinib therapy. The nomogram, not externally validated, is best used as a screening aid to identify patients who may benefit from intensified cardiovascular monitoring. Full article

Post-traumatic stress disorder (PTSD) is associated with immune and autonomic disturbances, but molecular programs linking PTSD-related blood transcriptional signals with autonomic–cardiac biology remain incompletely characterized. The public Gene Expression Omnibus (GEO) cohorts analyzed here did not directly measure palpitations or autonomic dysfunction. Peripheral-blood transcriptomes from GSE81761 and GSE63878 were integrated with a prespecified pathway-derived autonomic–cardiac gene set constructed from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Genes overlapping the curated pathway set were assessed using functional enrichment and protein–protein interaction (PPI) analyses. Multi-algorithm comparison and a separate random-forest/SHapley Additive exPlanations (SHAP) analysis were performed for internal model assessment and biological prioritization. GSE64813 and GSE97356 were analyzed using targeted single-gene analyses and cohort-specific multivariable logistic models. Model performance was examined using repeated nested cross-validation, a fully nested sensitivity analysis, and locked-transfer testing to GSE64813 and GSE97356. Interleukin 15 (IL15) and protein phosphatase 2 scaffold subunit Aalpha (PPP2R1A) were evaluated using external-cohort analyses, immune-cell deconvolution, and descriptive postmortem hippocampal single-nucleus data. Among 1679 nominally significant PTSD-associated candidate genes, 92 overlapped the curated pathway set and were enriched for cytokine signaling, chemotaxis, apoptosis, calcium transport, and PP2A-related functions. PPI analysis yielded 37 recurrent candidate hub genes. The original model comparison ranked support-vector machine (SVM) the highest across the merged and source-cohort summaries [mean area under the receiver-operating-characteristic curve (AUC) 0.853], but these estimates represent internal discovery-stage performance. IL15 was recurrently prioritized by network-based analyses, whereas PPP2R1A was a component of an enriched phosphatase-related module. IL15 and PPP2R1A showed modest single-gene effects in GSE64813 (AUC 0.566 and 0.612) and GSE97356 (AUC 0.558 and 0.593). Cohort-specific refitted models showed apparent AUC values of 0.834 and 0.749, respectively. Repeated nested cross-validation conditional on the preselected 29-gene feature set identified L2-regularized logistic regression as the best-performing algorithm (mean AUC = 0.690). Importantly, a more stringent fully nested sensitivity analysis, in which differential-expression screening and pathway intersection were repeated within each outer training fold, yielded a mean repeated outer-cross-validated AUC of 0.593 [standard deviation (SD) = 0.033; range, 0.541–0.625], indicating limited predictive performance. Locked-transfer AUCs were 0.664 in GSE64813 and 0.534 in GSE97356. Single-nucleus summaries suggested donor- and nucleus-type-dependent expression patterns for IL15 and PPP2R1A. These findings identify IL15-related cytokine signaling and PPP2R1A-related phosphatase regulation as candidate molecular programs linking PTSD-associated transcriptional variation with pathway-derived autonomic–cardiac biology. The results should therefore be interpreted as hypothesis-generating rather than direct molecular evidence for unmeasured palpitation symptoms. Prospective validation in independent, clinically well-characterized cohorts with standardized autonomic and cardiac phenotyping is warranted. Full article

Background: Antimicrobial-resistant Salmonella enterica from chicken sources is an important One Health concern because poultry can serve as a route for transmission of resistant foodborne pathogens. This study analyzed whole-genome sequencing data from 4611 chicken-associated Salmonella enterica isolates in the United States from the National Center for Biotechnology Information (NCBI) Pathogen Isolates Browser across seven antimicrobials: tetracycline, streptomycin, sulfisoxazole, ampicillin, ceftriaxone, nalidixic acid, and chloramphenicol. Methods: Principal component analysis, hierarchical clustering, and frequency-based bar-plot analysis were used to characterize gene-occurrence patterns and prioritize antimicrobial resistance (AMR), virulence, and stress-response genes. These prioritized genes were evaluated by logistic regression, and genotype–phenotype discrepancy analysis examined resistant isolates lacking expected antimicrobial-specific AMR genes using Fisher’s exact tests with Benjamini–Hochberg false discovery rate correction. Results: Resistant isolates shared broad genomic features: mdsA and mdsB were the most frequently detected AMR genes across all seven groups; virulence genes including invA, iroB, iroC, sinH, pipA, and avrA were repeatedly prominent; and golS, golT, and asr formed a common stress-response background. In the logistic regression models that predicted the probability that each Salmonella enterica isolate was resistant to a specific antimicrobial based on the presence or absence of selected genes, AMR-only models showed area under the receiver operating characteristic curve (AUC) values of 0.926–0.995, combined virulence and stress-response models showed AUC values of 0.826–0.990, and models combining all three gene categories showed AUC values of 0.935–0.998. Discrepant isolates were uncommon (0.06–2.10%), but enriched virulence and stress-response genes included recurrent pco, sil, spv, and steB signals across multiple antimicrobial groups. Conclusions: These findings identify resistance-associated genomic backgrounds involving virulence and stress-response genes and demonstrate their predictive value when incorporated into gene-based models. The enriched genes provide candidates for future genomic and experimental investigations to test whether they contribute functionally to antimicrobial resistance, persistence, or co-selection in poultry-associated Salmonella enterica. Full article

If Recirculating Aquaculture Systems (RAS) are widely regarded as one of the most promising technologies for sustainable aquaculture, why has their commercial adoption remained relatively limited in countries such as Brazil? Despite the remarkable scientific progress achieved in RAS technology over the past decade, a significant gap remains between experimental advances and their widespread commercial implementation. Most published studies have focused on optimising individual system components, including biofiltration efficiency, water quality management, feeding strategies, functional additives, microbial communities, and fish performance under controlled experimental conditions. Although these studies have substantially advanced our understanding of RAS operation, relatively few have critically evaluated whether the reported technological improvements remain effective, economically viable, or operationally feasible when transferred to commercial production systems. Consequently, many innovations that demonstrate promising biological outcomes at laboratory or pilot scales have yet to be validated under the technical, economic, and logistical constraints faced by commercial aquaculture enterprises. The Brazilian evidence indicates a heterogeneous but increasingly mature scientific landscape. Shrimp production provides relatively strong evidence for intensive RAS, biofloc, low-water-exchange, and integrated systems, whereas marine fish and mollusc production remains more strongly concentrated on experimental and pilot-scale optimisation. The future of RAS will not depend solely on further technological innovation, but on the successful integration of biological performance, engineering efficiency, economic feasibility, and practical scalability into commercially viable production systems. Full article

In the highly dynamic production environment of intelligent logistics centers, autonomous mobile robots (AMRs) serve as the core carriers connecting automated storage systems with assembly lines. Their operational efficiency directly determines the overall production cycle of the entire facility. In actual working conditions, narrow aisles in line-side material stacking zones often lead to local deadlocks. Additionally, the presence of mixed human–machine traffic and numerous dynamic obstacles causes traditional algorithms to struggle with obstacle avoidance or path oscillation during long-distance delivery. This paper investigates the M150 warehouse mobile robot and proposes an improved Dynamic Window Approach (DWA) integrated with adaptive fuzzy control for local path planning. First, the velocity evaluation function is modified for confined spaces by incorporating angular velocity to enhance escape capability and adding a target distance function to optimize sub-goal tracking. Second, a dynamic sampling space based on obstacle distance is constructed to balance computational load. Finally, a two-input, four-output fuzzy controller is designed to adaptively adjust evaluation function weighting factors in real time, enhancing the AMR’s adaptability across diverse scenarios. MATLAB-based simulations demonstrate that compared to traditional algorithms, the improved DWA produces smoother trajectories, effectively resolving jamming and obstacle avoidance issues, thereby meeting enterprises’ stringent requirements for AMR operational stability and safety. Full article

Background/Objectives: Aldehyde dehydrogenase 2 (ALDH2) detoxifies acetaldehyde, and impaired ALDH2 activity has been implicated in carcinogenesis. The acetaldehyde breath test (ABT) enables noninvasive functional assessment of ALDH2 activity, but its association with pancreatic disease remains unclear. We examined associations between ABT-assessed ALDH2 activity and pancreatic disease outcomes. Methods: This case–control study included 287 health checkup participants, 131 patients with benign pancreatic disease, and 65 patients with pancreatic cancer. Participants underwent ABT, and the acetaldehyde-to-ethanol (A/E) ratio was calculated. The ALDH2 inactive phenotype was defined as an A/E ratio ≥ 23.3. Multinomial logistic regression used health checkup participants as the reference. Results: The median A/E ratio was higher in patients with benign pancreatic disease and pancreatic cancer than in health checkup participants (21.7 and 24.2 vs. 13.6; p < 0.001). The ALDH2 inactive phenotype was associated with benign pancreatic disease (relative risk ratio [RRR], 3.55; 95% confidence interval [CI], 1.85–6.83) and pancreatic cancer (RRR, 4.82; 95% CI, 2.13–10.88). The highest A/E ratio category was also associated with benign pancreatic disease (RRR, 8.77; 95% CI, 3.59–21.39) and pancreatic cancer (RRR, 12.79; 95% CI, 4.41–37.09). Exploratory spline analyses showed associations between higher A/E ratios and pancreatic disease outcomes without clear evidence of nonlinearity. Conclusions: A higher ABT-derived A/E ratio was associated with benign pancreatic disease and pancreatic cancer in this selected case–control study. Prospective studies are needed to determine whether functional assessment of aldehyde metabolism provides clinically useful information for pancreatic disease risk assessment. Trial registration number: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000052609; registered 1 November 2023. Full article

With limited bed availability at Malta’s state-run rehabilitation hospital, efficient and accurate assessment of frail older adults is essential for appropriate inpatient geriatric rehabilitation (GR) admissions. This study aimed to identify key predictors influencing admission decisions for inpatient GR programmes in Malta. Prospective data were collected from 250 patients aged 60 and over. In total, 83 predictors, including demographic details, clinical history, functional levels and social factors, were analysed against admission outcomes. Logistic regression analysis, mainly univariate analysis, followed by multivariate analysis with backward stepwise elimination, was used to determine significant predictors. Seven key predictors were identified, which shed light on the decision-making processes of the assessing specialists, highlighting the importance of embracing the ICF model rather than relying solely on medical criteria. These predictors reflect the WHO ICF and CGA frameworks, supporting a holistic, patient-centred approach. They informed the development of a digital tool, incorporating a future predictive model to guide GR admission decisions in Malta, aiming to facilitate the delivery of stratified and personalised care by enabling clinicians to select a care pathway based on the patient’s potential health trajectory in response to rehabilitation interventions. Full article

Background and Objectives: Bethesda Category IV thyroid nodules present a diagnostic challenge due to their variable risk of malignancy and uncertain cytological features. Therefore, determining the risk of malignancy before surgery is important. This study aims to identify clinical, biochemical, and ultrasonographic factors associated with malignancy and to explore the performance of a multivariable analysis based on routinely available preoperative features in thyroid nodules. Methods: This retrospective, single-center study included 105 patients who underwent thyroidectomy for Bethesda Category IV cytology. The mean age was 50.13 ± 11.78 years. 87 patients (82.9%) were female, and 18 (17.1%) were male. Patients were classified into benign/borderline (n = 79) and malignant (n = 26) groups based on their postoperative histopathological findings. Demographic characteristics, serum thyroid function tests, thyroid autoantibody levels, and ultrasonographic findings were compared. Variables significantly associated with malignancy were included in a Firth bias-reduced penalized multivariable logistic regression analysis. The discriminative performance of the multivariable analysis was evaluated using ROC curve analysis, and internal validation was performed using bootstrap resampling. The AUC was compared with that of ACR TI-RADS using DeLong’s test. Results: The malignant group showed a significantly higher prevalence of male sex, irregular margins, a taller-than-wide shape, and microcalcification (all p < 0.05). In the multivariable logistic regression analysis, only irregular margins (OR = 9.46, 95% CI: 1.88–47.59; p = 0.006) were independently associated with malignancy. The model demonstrated acceptable discrimination in this study population (n = 105), with an AUC of 0.717. The AUC of the multivariable analysis was 0.717, compared with 0.704 for ACR TI-RADS, and the difference was not statistically significant (ΔAUC = 0.013; DeLong p = 0.803). Conclusions: In Bethesda Category IV thyroid nodules, irregular margins remained independently associated with malignancy. The multivariable analysis did not demonstrate significantly better discrimination than ACR TI-RADS. These findings should be considered exploratory and require external validation in larger cohorts. Full article

This study investigates the stress behavior of the L-shaped pipeline elbows at LNG receiving terminals. A finite element model is developed to investigate the effects of internal pressure, temperature, and their coupling on the stress field at the 45° cross-section of the elbow. The numerical result is compared with experimental results to evaluate its accuracy. For internal pressure loading alone, the peak stress is governed by hoop tension and located at the intrados. In contrast, under thermal loading alone, compressive hoop stress shifts the critical location to the crown. When both loads are applied simultaneously, competition between two high-stress zones causes the peak location to jump among 0°, 57°, and 83° as the relative dominance of thermal and pressure effects varies, challenging conventional fixed-location inspection strategies. A response surface model is constructed to predict extreme stress magnitudes, and multinomial logistic regression is employed to establish quantitative classification boundaries for the peak stress location as a function of temperature and pressure. Within the investigated range, the critical pressures predicted by the logistic regression model agree well with the finite element results. These findings provide a predictive basis for risk-based inspection prioritization and failure probability assessment of cryogenic pipeline elbows under operational thermal-pressure conditions. Full article