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Analytic solutions for Euler–Bernoulli beams with axial compression resting on a nonlinear elastic foundation using MADM
Abstract This article investigates the deflection behavior of Euler–Bernoulli beams subjected to axial compression and resting on a nonlinear elastic foundation. The Modified Adomian Decomposition Method (MADM) is employed to predict the beam deflection under various loading and foundation conditions. By adopting an initial polynomial ansatz, MADM effectively optimizes the construction of Adomian polynomials, resulting in rapid convergence and an accurate series solution. The accuracy and reliability of the proposed method are examined through two illustrative cases. In the first case, the formulation is verified against an analytically tractable benchmark problem, while in the second case, the MADM results are compared with previously published solutions. The comparative analysis demonstrates excellent agreement with existing studies, confirming the validity of the proposed approach. Overall, the results indicate that MADM provides a stable and efficient analytical framework for modeling the coupled effects of axial compression and nonlinear elastic foundations in Euler–Bernoulli beams.
Integrated computational and experimental immunoengineering of adeno-associated virus capsid T cell epitopes in mice
Abstract Adeno-associated virus (AAV) vectors are widely used in gene therapy, but their immunogenicity remains a significant challenge, limiting long-term efficacy and the feasibility of repeated administration. In this study, we combine computational prediction with experimental validation to engineer AAV9 capsids with reduced immunogenicity. To facilitate this, we developed the Epitope Modification and MHC Prediction (EMMP) pipeline, which systematically automates the evaluation of amino acid substitutions for their predicted effects on major histocompatibility complex (MHC) presentability. Using this pipeline, we modify a CD4⁺ T-cell epitope in the AAV9 capsid that is identified and characterized as a proof-of-concept. Two mutant variants, R312H and R312Q, are selected and evaluated for transduction efficiency in vitro and immune response modulation in vivo. Notably, R312Q shows a significant reduction in T-cell activation and anti-AAV9 antibody production, albeit with a slight reduction in transduction at low multiplicities of infection (MOI). These results demonstrate a rational approach for optimizing AAV vector design, with potential applications for improving the safety and efficacy of gene therapy.
The relationship between maternal glucose concentrations, gestational diabetes mellitus, placental weight, and placental vascular malperfusion lesions: A retrospective study of a U.S. pregnancy cohort
Background Gestational diabetes mellitus (GDM) is associated with increased placental weight and the presence of placental malperfusion lesions, likely related to high blood glucose. The relationship between high glucose without overt GDM, and placental characteristics is not well understood. Objective To examine the relationships between glucose challenge test (GCT) concentrations, GDM, and placental characteristics associated with GDM. Methods We conducted a secondary analysis of medical record data from singleton placentas sent to pathology at Northwestern Memorial Hospital (2011–2022; n = 11,585). Placentas were submitted based on standard clinical protocol. Data included maternal demographic variables, GCT concentrations, GDM diagnosis, placental weight, and vascular malperfusion lesions (accelerated villous maturation, increased syncytial knots, delayed villous maturation, and increased perivillous fibrin deposition). We classified GCT <140 mg/dL as pass and ≥140 mg/dL as fail. GDM was classified by diagnosis. We categorized glucose groups into pass GCT/no GDM , fail GCT/no GDM , and GDM . We used linear and Poisson (due to non-convergence of log-binomial) regression models to examine the association between GCT concentrations or groups with placental outcomes, adjusting for maternal age, race and ethnicity, parity, gestational age at delivery, and infant sex. Results Of placentas sent to pathology, 17% were in the fail GCT/no GDM group and 5% were in the GDM group. Compared to the pass GCT/no GDM group, the adjusted mean placental weight was heavier by 13.6 grams [95% CI: 8.8, 18.3] in the fail GCT/no GDM and 22.0 grams [13.8, 30.2] in the GDM group. Patients diagnosed with GDM had a 36% [2%, 81%] increased adjusted risk of delayed villous maturation compared to the pass GCT/no GDM . The risk of the other lesions (accelerated villous maturation, increased syncytial knots, and increased perivillous fibrin deposition) was not significantly different between groups. Conclusion GDM and high glucose concentrations without GDM were associated with heavier placentas. Patients with GDM had a higher risk of delayed villous maturation, but risk of other placental lesions was similar.
Investigation of varenicline and tropisetron in latent inhibition and novel object recognition in mice
Abstract There is currently no treatment for cognitive-impairment associated with schizophrenia (CIAS). Animal and human studies suggest that nicotinic cholinergic agonists and 5-HT3 antagonists have potential therapeutic benefits. We investigated whether co-administration of varenicline, an alpha4beta2 nAChR partial agonist and alpha7 nicotinic receptor agonist, and tropisetron, a 5-HT3 antagonist and alpha7 nicotinic receptor agonist is pro-cognitive in male c57/Bl6 mice. We first assessed Latent inhibition (LI) an associative learning process of learning to ignore irrelevant stimuli. We report no effect of tropisetron on LI (0.01, 0.04, 0.4 mg/kg s.c.). Varenicline at 0.5 mg/kg s.c. potentiated LI. Co-administration of tropisetron 0.4 mg/kg s.c. and 0.5 mg/kg s.c. varenicline abolished varenicline’s potentiation of LI. In 24 h retention of novel object recognition (NOR) where memory performance (discrimination-index) is poor in controls there was no effect of varenicline or tropisetron. When varenicline (0.5 mg/kg) and tropisetron (0.01, 0.1, 1.0 mg/kg) were co-administered NOR discrimination-index was higher compared to controls. These data indicate that varenicline enhances LI when low in controls, demonstrate an interaction between varenicline and tropisetron in LI and suggest synergistic interaction between tropisetron and varenicline to potentiate NOR memory merits further investigation. These findings have implications for treatment of CIAS and disorders with cognitive impairment.
Contrast-free identification of glioma blood-brain barrier status via generative diffusion AI and non-contrast MRI
Exploring the relationship between mental health and urban green space soundscapes: A scoping review
Urban soundscapes, particularly those experienced in green spaces, have been increasingly recognized as factors that influence human mental health. This scoping review explores the existing literature on soundscapes within urban green spaces and their associated mental health outcomes. It aims to classify the methodologies used in this domain, identify mental health outcomes related to urban green space soundscapes, and examine specific soundscape elements and their correlations with mental health. A systematic search of peer-reviewed studies was conducted. After screening titles, abstracts, and full texts, 22 studies met the inclusion criteria. Diverse methodological approaches were identified, with an emphasis on quantitative multi-method designs. Commonly studied mental health outcomes include stress reduction, mood enhancement, perceived restorativeness, and cognitive restoration. Standardized psychometric tools, such as the Perceived Stress Scale (PSS-14), Positive and Negative Affect Schedule (PANAS) and Perceived Restorativeness Soundscape Scale (PRSS) are frequently used as outcome measures. Natural soundscape elements such as birdsong, water sounds, and rustling leaves had a positive association with relaxation and perceived mental restoration throughout all studies, while mechanical sounds, such as traffic noise were linked to adverse mental health outcomes. These findings highlight that natural soundscapes in urban green spaces have a potential positive relationship with mental health by reducing stress and enhancing mood. However, the cross-sectional design and methodological heterogeneity of the included studies limit causal interpretation. Future research should explore multi-sensory experiences and examine soundscapes in diverse urban contexts to provide more robust insights into their relationship with mental health. The practical implications suggest that urban planners should prioritize integrating natural sound elements into urban areas to improve mental health. The study protocol of this scoping review had been registered at OSF (osf.io/4r7gd).
Analysis of chemiluminescence and liquid chromatography-mass spectrometry in 25-hydroxyvitamin D detection using fuzzy logic
Abstract Vitamin D is an essential nutrient closely associated with the prevention of multiple diseases, including osteoporosis, diabetes, and cardiovascular disorders. The serum level of 25-hydroxyvitamin D [25(OH)D] is the primary biomarker for assessing vitamin D status, and its precise quantification is critical for clinical diagnosis and treatment. Chemiluminescence immunoassay (CLIA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) are widely used analytical methods; however, methodological discrepancies often lead to inconsistent results that may be further influenced by demographic factors such as age and gender. In this study, we evaluated the consistency and correlation between CLIA and LC-MS/MS measurements using a Generative Fuzzy Inference System (GENFIS). Analysis of 138 serum samples showed that LC-MS/MS produced significantly higher 25(OH)D concentrations than CLIA ( p < 0.01; mean difference = 1.33 ± 3.71; 95% CI: − 5.95 to 8.61), though the two methods exhibited strong linear correlation and agreement (Cohen’s Kappa = 0.8257; R² = 0.9075; intraclass correlation coefficient = 0.93). GENFIS analysis indicated a possible 30–40-year female pattern of larger between the detection differences of two methods. To verify this finding, an additional 59 samples were analyzed, revealing a relative risk (RR) of 3.18 (95% CI: 1.71–5.93; p < 0.05) for this subgroup compared with other populations, supporting the GENFIS inference. These results highlight age- and gender-related differences in 25(OH)D measurement between CLIA and LC-MS/MS, providing valuable insights for improving the standardization and clinical interpretation of vitamin D testing.
Bayesian machine learning enables discovery of risk factors for hepatosplenic multimorbidity related to schistosomiasis
Abstract One in 25 deaths worldwide is related to liver disease, and often with multiple hepatosplenic conditions. Yet, little is understood of the risk factors for hepatosplenic multimorbidity, especially in the context of chronic infections. We present a novel Bayesian multitask learning framework to jointly model 45 hepatosplenic conditions assessed using point-of-care B-mode ultrasound for 3155 individuals aged 5-91 years within the SchistoTrack cohort across rural Uganda, where chronic intestinal schistosomiasis is endemic. We identify distinct and shared biomedical, socioeconomic, and spatial risk factors for individual conditions and hepatosplenic multimorbidity, and introduce methods for measuring condition dependencies as risk factors. Notably, for gastro-oesophageal varices, we discover key risk factors of older age, lower haemoglobin concentration, and schistosomal periportal fibrosis. Our findings provide a compendium of risk factors to inform surveillance, triage, and follow-up, while our model enables improved prediction of hepatosplenic multimorbidity, and if validated on other anatomical systems, general multimorbidity.
Assessment of physical status and analysis of lipidomic and metabolomic alterations in patients with Post-COVID-19 condition
The development and persistence of symptoms following SARS-CoV-2 infection, known as Post-COVID-19 Condition (PCC) or “long COVID,” represents a global health challenge. In this prospective cross-sectional study, we conducted a detailed assessment of the physical condition of 46 patients using handgrip dynamometry, ergoespirometry, and the 6-minute walk test (6MWT). The results revealed a loss of muscle strength and poor exercise tolerance primarily due to peripheral muscle involvement. To complement and better understand these findings, we compared the blood metabolome and lipidome of 13 patients with PCC, 13 patients with acute COVID-19 infection, and 13 healthy controls using magnetic resonance spectroscopy (1H-NMR). PCC patients showed lower levels of HDL-cholesterol, as well as medium and dense HDL particles, which could contribute to a pro-atherogenic and pro-inflammatory state. Although no significant differences were observed in glycoproteins, we found decreased glucose and increased lactate levels, supporting the hypothesis of mitochondrial dysfunction in PCC patients. Additionally, elevated glycine and reduced glutamate levels may be related to the neurological symptoms associated with the condition. We also observed increased levels of glutamine, leucine, and isoleucine, indicating protein hypercatabolism and metabolic stress. These findings suggest that alterations in the metabolome and lipidome of PCC patients may be contributing to the persistence of their symptoms.
Hybrid EfficientNet B4 and SVM framework for rapid and accurate bone cancer diagnosis from X-rays
Abstract The early and correct diagnosis of bone cancer is important for treating both primary and metastatic conditions effectively. Traditional imaging techniques, like CT, MRI, and X-ray scans, depend exclusively on manual review, which is time-consuming and prone to human errors. Recently, ML and DL have enabled automated diagnostic systems that are more accurate, reliable, and efficient. Still, many of the existing approaches using DL suffer from high computational complexity, overfitting, and limited availability of robust datasets. This work proposes a novel diagnostic model for bone cancer, called OsteoCancerNet, which combines EfficientNetB4 for feature extraction with a support vector machine using the RBF kernel for classification. EfficientNetB4 captures efficiently both quantitative and qualitative features from X-ray images, and the SVM ensures robust binary classification. Extensive experiments using a large dataset with 29,952 X-ray images demonstrate that OsteoCancerNet provides 98% precision, 97.47% recall, 98% accuracy, and a 98% F1-score, thus outperforming traditional machine learning, deep learning, and transfer learning methods. Of note, the model maintains fast inference times of 41 milliseconds per image, making it suitable for real-time clinical applications. By combining deep learning feature extraction with traditional machine learning classification, OsteoCancerNet provides an efficient, accurate, and practical approach for the early detection of bone cancer. This approach has the potential to aid radiologists in timely diagnosis, decrease workload, and improve treatment outcomes, thus underlining the advantages of integrating DL and ML techniques within medical imaging. Keywords: OsteoCancerNet; computer-assisted diagnosis; bone cancer diagnosis; EfficientNet B4 model; SVM model; X-ray image analysis.
Machine learning helps to strongly reduce future warming uncertainty
Real-world clinical effectiveness of trimethoprim–sulfamethoxazole for primary prophylaxis of pneumocystis pneumonia in non-hodgkin lymphoma patients treated with rituximab
There are no definitive clinical practice guidelines regarding the necessity and dosage of trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in individuals undergoing rituximab therapy. This retrospective study evaluated the effectiveness and safety of various TMP–SMX prophylactic dosing regimens over a 1-year period in 690 patients with non-Hodgkin lymphoma treated with rituximab at a university hospital in Thailand from 2013 to 2022. Out of these patients, 622 (90.1%) received TMP/SMX, with a mean duration of prophylaxis of 265.7 days (SD 85.66). The overall incidence of PJP was 1% (7 patients), which was significantly higher in the non-prophylaxis group (5.8%, 4 patients) compared to the prophylaxis group (0.6%, 3 patients). No cases of PJP occurred among those receiving standard prophylaxis or a single-strength tablet every other day, three times a week. However, instances in the prophylaxis cohort were reported in patients who took two single-strength tablets twice daily, twice a week. Prophylaxis resulted in a significant reduction in the one-year incidence of PJP, with a hazard ratio of 0.105 (95% CI: 0.023–0.469). Mild adverse reactions were noted in 3.05% of patients, all of whom recovered. These findings suggest that TMP/SMX prophylaxis was associated with a lower incidence of PJP and was well tolerated. Future studies should explore optimal dosing strategies while considering patient selection bias and concurrent immunosuppressive therapy.
Toward robust automated cardiovascular arrhythmia detection using self-supervised learning and 1-dimensional vision transformers
Alpha frequency shapes perceptual sensitivity by modulating optimal phase likelihood
Do whale-watching experiences and tourist expectations align? A comparison of three Macaronesian destinations
This study examines the alignment between whale-watching experiences and tourist expectations in three different destinations. Whale-watching is a global tourist activity, with locations such as the Canary Islands (Spain) and the Azores (Portugal) in Macaronesia rapidly becoming prime spots for these marine activities. Those locations attract a significant number of tourists with varying recreational interests and diverse perceptions of each destination and its natural resources, including marine wildlife megafauna species that can be seen. While often marketed as sustainable tourism, the ecological impacts of whale-watching are a matter of concern. Evolving whale-watching practices may reinforce or diminish the effectiveness of conservation and environmental education efforts. In this regard, exploring whale watchers’ expectatives, preferences, previous experiences, level of satisfaction, and environmental information may help to assess better practices and sustainable tourism initiatives. This study employed a multidisciplinary approach, incorporating a series of questionnaires that explored whale watchers’ expectations and overall satisfaction before and after sea trips in the Tenerife and El Hierro Islands (Canary Islands, Spain), as well as in São Miguel (Azores, Portugal). The findings highlight differences across three study cases: El Hierro attracted more experienced and oriented tourists, while Tenerife and São Miguel received more generalist visitors. Satisfaction was closely linked to the number of cetacean sightings. Many participants who did not mention specific species expressed open preferences such as wanting to “see everything” or “whatever is possible”, reflecting limited prior knowledge. The study highlights the importance of tailoring whale-watching strategies to tourist profiles by enhancing communication, adjusting group sizes and vessel types, and reinforcing conservation messaging to ensure both positive experiences and long-term ecological sustainability.