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Characterization of the random positioning machine as a microgravity simulator for biological applications
Simulated microgravity platforms provide essential tools for studying gravitational effects on biological systems under controlled laboratory conditions. The Random Positioning Machine (RPM) is among the most commonly used ground-based simulators, yet quantitative evaluations of its mechanical performance and biological effects remain limited. This study provides a comprehensive mechanical and biological characterization of an RPM device capable of operating in randomized, unidirectional, and single-axis clinostat modes. Angular velocity profiles were experimentally recorded using magneto-inertial measurement units mounted on the RPM frames. These data informed a computational model that simulated gravity vector dispersion and centrifugal acceleration across different operational configurations. Additionally, SH-SY5Y neuronal cells were exposed to simulated microgravity under each mode to evaluate cellular responses. The computational analysis demonstrated that all RPM modes effectively achieved simulated microgravity conditions, with time-averaged gravity values ranging from 10 −2 to 10 −3 g. Centrifugal accelerations remained below 0.08 g across all conditions. Biologically, SH-SY5Y cells exposed to simulated microgravity exhibited reduced confluency and increased α-synuclein inclusions in all RPM configurations, with milder effects observed in clinostat mode. The integration of experimental, computational, and biological analyses establishes a quantitative framework for assessing and optimizing RPM-based microgravity simulations. The findings confirm that both RPM and clinostat modes can reproduce key features of microgravity, while highlighting the role of motion characteristics in shaping biological responses. The proposed computational model represents a predictive tool to support the design and reproducibility of future ground-based microgravity studies.
Characterisation of the chloroplast genome of Macrotyloma species: comparative analysis and phylogenomic insights
Risk prediction of <i>Helicobacter pylori</i> strains across Correa’s cascade via intelligent analysis of genome-wide SNPs
Only a minority of Helicobacter pylori ( H. pylori )-infected individuals progress along Correa’s cascade, and classical virulence markers do not fully explain this heterogeneity, motivating genome-wide approaches to quantify strain-level genomic risk associated with advanced lesions. We assembled 528 high-quality H. pylori whole-genome sequences spanning nonatrophic gastritis (NAG), atrophic gastritis (AG), intestinal metaplasia (IM), and gastric cancer (GC) and performed bacterial genome-wide association analyses with explicit adjustment for population structure. We then integrated advanced lesions-associated variants into a random forest model to derive an H. pylori Genomic Risk Score (HpRS), defined as the predicted probability that a strain is associated with advanced lesions (IM/GC) vs. nonadvanced lesions (NAG/AG). Despite phylogenetic analyses revealing that genome-wide clustering was primarily driven by geographic lineage rather than disease stage, HpRS achieved strong discrimination in repeated cross-validation (mean AUC = 0.902, 95% CI: 0.892 to 0.912), remained discriminatory in an internal held-out set (AUC = 0.780), and generalized to two independent cohorts (Bacterial and Viral Bioinformatics Resource Center (BV-BRC): AUC = 0.871; hospital cohort distinguishing IM vs. NAG/AG: AUC = 0.843). Predictive single-nucleotide polymorphisms mapped mainly to core functions (DNA repair, translation, and central and lipid metabolism) and often affected conserved domains, suggesting a polygenic architecture and generating testable functional hypotheses. HpRS provides a proof-of-principle framework for strain-aware risk stratification and may complement future gastric cancer prevention strategies.
Data subdivision approach enhances machine learning-based mortality prediction in pediatric ICU patients
Objective To evaluate machine learning–based models for predicting all-cause mortality in pediatric ICU patients using comprehensive biochemical panels, with a focus on addressing missing data and class imbalance. Materials and methods A retrospective analysis was performed on a publicly available PICU dataset comprising 8,629 patients aged 28 days to 18 years. Twenty-two biochemical variables measured on the first PICU day were analyzed. Missing values were addressed using Multiple Imputation. Lasso regression was applied for feature selection. Models were trained using 5-fold cross-validation with the Synthetic Minority Oversampling Technique (SMOTE). Two ML-based imbalance-handling strategies, stacking ensemble and data subdivision were evaluated. Pairwise DeLong tests were used to compare AUC performance across models. Results Among the 8,629 included patients, there were 476 non-survivors (5.5 percent). Multiple imputation followed by SMOTE improved model performance across all algorithms. The single-model classifiers achieved AUC-ROC values of 0.82 (Random Forest), 0.79 (CatBoost), 0.83 (Extra Trees), and 0.79 (Logistic Regression). The stacking ensemble demonstrated the best overall performance, with an AUC-ROC of 0.88 and an AUC-PRC of 0.45. The data subdivision approaches also produced strong discriminative performance, achieving AUC-ROC value up to 0.83 for three-subdivision, and 0.82 for five-subdivision strategies. Calibration analysis showed that the stacking model achieved the lowest Brier score (0.04), indicating superior probabilistic accuracy compared with individual classifiers. Feature importance analyses across all MI-based models consistently highlighted coagulation markers (D-dimer, reference TT, PTT, INR), electrolytes (chloride, potassium, sodium), and metabolic and organ-dysfunction indicators (AST, ALT, creatinine) as key predictors of mortality. Conclusions This study demonstrates that ensemble stacking is a more effective strategy than data subdivision for addressing class imbalance in PICU mortality prediction.
Cuboid height measured using ultrasound is related to sex and dorsal arch height
A polymerase ribozyme increases copying fidelity through pyrophosphate-mediated RNA repair
Prior to the emergence of the contemporary biosphere, the first replicating systems are thought to have progressed through an RNA-based stage. Such an evolving world would likely have transferred heritable information during replication using RNA polymerase ribozymes. Though substantial effort has been put forth toward evolving RNA polymerases, many variants suffer from premature termination and low fidelity, resulting in low yields of full-length or active sequences. Replication of longer sequences requires a sufficiently high fidelity to lend an evolutionary advantage to an evolvable system. Here, we demonstrate ribozyme-mediated repair of mismatched and damaged RNA sequences. Under conditions of saturating pyrophosphate concentrations, we show that a polymerase ribozyme can repair RNA sequences terminated in a mismatch to generate a triphosphorylated nucleoside, such as adenosine triphosphate, which we detect directly. Similarly, the ribozyme can remove a nucleotide with a nonextendable 2′-3′ cyclic phosphate or a nonextendable mismatch. This repair step increases the overall fidelity of RNA synthesis and allows polymerization along an extended template. The increased copying fidelity advances the long-standing goal of developing a self-replicating polymerase ribozyme.
Preparation and in vitro evaluation of photodynamic-responsive nanoliposome loaded PL-5
Burn wound infections are frequently complicated by biofilm-forming and multidrug-resistant pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), posing major therapeutic challenges. Antimicrobial peptides (AMPs) such as PL-5 (peceleganan) exhibit broad-spectrum activity but are limited by instability, poor biofilm penetration, and reduced efficacy in complex wound environments. Here, a red-light-responsive, porphyrin-phospholipid (PoP)-containing cationic liposomal system for PL-5, aiming to enhance its antibacterial and antibiofilm performance was developed. Optimized liposomes achieved high encapsulation efficiency (~73%), uniform nanoscale size (~50 nm), narrow polydispersity, and positive surface charge. They demonstrated good storage stability and controlled peptide release under red-light irradiation (635 nm). In vitro , red-light activation significantly enhanced antimicrobial activity against MRSA and methicillin-susceptible S. aureus (MSSA), reducing minimum inhibitory concentration (MIC) values fourfold and accelerating bactericidal kinetics compared with free PL-5 and non-irradiated liposomes. Additionally, red-light-activated liposomes markedly inhibited biofilm formation. These results indicate that light-responsive liposomal delivery enables spatiotemporally controlled release of PL-5, significantly potentiating its antibacterial and antibiofilm efficacy. This approach offers a promising localized treatment strategy for biofilm-associated burn wound infections and a foundation for future translational studies.
Record growth of stratospheric aerosols from 2019 Raikoke eruption with sulfate-coating of submicronic ash
A fungal natural product that inhibits plant cellulose biosynthesis by disrupting cellulose synthase complexes
Cellulose, a primary component of plant cell walls, is synthesized by cellulose synthase complexes (CSCs) at the plasma membrane. Targeting this process with cellulose biosynthesis inhibitors (CBIs) has significantly advanced our understanding of plant cell wall formation and provided valuable compounds for herbicide development. Here, we identified a fungal natural product, 8-methyldichlorodiaporthin (MDD), as a broad-spectrum plant CBI. Structure–activity relationship analyses demonstrate that methylation modifications on the isocoumarin ring and chlorination of the side chain are crucial for MDD-induced growth inhibition. A chemical forward genetic screen in Arabidopsis thaliana revealed two semidominant CESA1 mutations, causing A903T and H1024Y substitutions, that confer insensitivity to MDD. Both mutations locate to transmembrane domains of CESA1, and we show that MDD depletes CSCs from the plasma membrane and reduces cellulose content. Further genetic analyses indicate that the cesa1 mddi1-1 A903T mutant also confers resistance to CBIs quinoxyphen and C17, but not to CBIs isoxaben, indaziflam, or ES20. Stacking additional point mutations conferring resistance to other CBIs, cesa3 ixr1-1 G998D , and cesa6 es20-r3 G935E into the cesa1 mddi1-1 A903T background yields multiple-drug-resistant lines that maintain normal growth. These findings establish MDD, as a natural CBI that likely targets CESA1, thereby extending our understanding of CSC regulation and abilities to develop multidrug-resistant crop varieties. These findings offer unique perspectives for weed management and plant biotechnology.
Understanding participants’ experiences of a behaviour change intervention within cardiac rehabilitation: A nested process evaluation within the STRENGTH randomised controlled trial
Background The STRENGTH (Self-management and Theory-based Rehabilitation Encouraging New Gateways to Healthy-Hearts) study evaluated a behaviour change intervention embedded within cardiac rehabilitation for individuals with coronary heart disease. This manuscript reports the process evaluation, which aimed to explore participants’ experiences of physical activity, barriers and facilitators to maintaining physical activity, and contextual and process-related factors influencing engagement with the intervention. Methods A process evaluation was nested within a two-arm cluster randomised controlled trial. Semi-structured interviews were conducted with participants from both intervention and control groups, focus groups were conducted with intervention participants. Thematic analysis examined factors influencing physical activity maintenance, including context, implementation, mechanisms of impact and perceived outcomes. Quantitative procedures measured intervention fidelity through attendance records and participant diaries. Results Both groups highlighted environmental, social, and personal factors influencing participation in cardiac rehabilitation, such as social support, professional oversight, and structured programming. Trainers and peer interactions were valued for motivation and perceived safety. The intervention group reported additional facilitators, including tailored support, external accountability, and self-monitoring, which increased awareness and reinforced adherence. Mechanisms of impact included increased awareness of physical activity, greater exercise confidence, and a sense of accomplishment. A perceived lack of exercise confidence may have hindered independent physical activity engagement. Conclusions While behaviour change strategies can enhance engagement in cardiac rehabilitation, their impact on measurable health outcomes remains unclear. Social support, professional oversight, and structured programming appear effective in maintaining physical activity levels, but future interventions should prioritise exercise confidence and education to promote sustained behaviour change. Trial registration Registered with ClinicalTrials.gov on 26-01-2023 (ID: NCT05705310 ).
Psychosocial factors associated with medication adherence among older adults with chronic diseases: an ITHBC-informed cross-sectional study
Abstract To identify psychosocial factors associated with medication adherence among elderly patients with chronic diseases, guided by the Integrated Theory of Health Behavior Change (ITHBC). A cross-sectional survey was conducted among 1,138 community-dwelling adults aged sixty years or older who were receiving long-term treatment for chronic diseases. A structured questionnaire was administered that incorporated validated instruments including the Adherence to Refills and Medications Scale (ARMS), the Medication Literacy Knowledge–Attitudes–Practices (KAP) Scale, the Beliefs about Medicines Questionnaire (BMQ), the Self-efficacy for Appropriate Medication Use Scale (SEAMS), and the Social Support Rating Scale (SSRS). Descriptive statistics, group comparisons, and binary logistic regression were used to examine the psychosocial factors associated with medication adherence. A total of 1,102 valid responses were obtained, yielding a response rate of 96.84%. Among the participants, 46.64% demonstrated good medication adherence. Guided by the ITHBC framework, psychosocial variables were categorized into intention-, capability-, and context-related domains. Logistic regression analysis showed that higher self-efficacy (OR = 0.874, p < 0.001) and higher medication literacy (OR = 0.980, p = 0.020) were associated with lower odds of poor medication adherence, whereas stronger medication concern beliefs (OR = 1.128, p = 0.008) and a history of adverse drug reactions (OR = 0.596, p = 0.035) were associated with poorer adherence. Compared with older adults living with a spouse, those living alone (OR = 3.848, p = 0.003) and those living with children (OR = 3.404, p = 0.004) showed significantly higher odds of poor medication adherence. Medication adherence among older adults with chronic diseases was associated with medication literacy, self-efficacy, social support, and medication beliefs. The ITHBC provided a useful framework for understanding these psychosocial determinants. The findings highlight the importance of multidimensional adherence-support interventions integrating medication education, psychosocial support, and self-management enhancement for older adults with chronic diseases.
Tuning bubble coalescence rates over orders of magnitude in liquid mixtures of simple surface thermodynamics: Experiments and theory
The coalescence time of bubbles in a liquid depends on the nature of the liquid, which determines both its surface thermodynamics and the molecular interactions between the gas/liquid interfaces, and on the geometry, prescribed by the curvature of the bubbles. Coalescence is well described in pure liquids that have the same composition in bulk and at interfaces and in which the interactions are attractive. In contrast, the mechanisms are poorly understood in more complex liquids in which coalescence times are orders of magnitudes larger than in pure liquids and are unpredictable. To provide insight on these mechanisms, we use model systems: binary mixtures of miscible oils. In these liquids, interfaces have purely attractive molecular interactions and the surface thermodynamics can simply be described using a well-determined Gibbs elastic modulus, which is controlled by the composition of the mixture. We measure the coalescence rate by forming periodic trains of bubbles in millifluidic tubes whose radius varies over 1.5 decade. We report coalescence times spanning more than three decades and, for a given composition, varying according to a power law with curvature, with an exponent larger than that reported in pure liquids and independent of Gibbs elasticity. The experimental behavior is in excellent agreement with a numerical solution of the coupled thermodynamical and hydrodynamical equations, performed in the simple geometry of a suspended liquid film. Our results clearly reveal how geometry and surface thermodynamics modify the coalescence process of bubbles in the limit of small Gibbs elasticity.
Transcatheter and surgical aortic valve replacement for aortic stenosis in France: Trends from 2010 to 2022 and impact of European guidelines and clinical trial results
Background The PARTNER trials played a key role in the expansion of transcatheter aortic valve replacement (TAVR) for severe aortic valve stenosis (AS), shaping international practice guidelines. We assessed the evolution of AS management in France between 2010 and 2022, and the impact of PARTNER trials and European guideline updates on TAVR use. Characteristics of patients, facilities and TAVR valves, and post-procedure events were also described. Methods and findings We conducted a nationwide cohort study using the French Health Data System (SNDS), including patients aged 18 years or older hospitalized for AS and receiving a first TAVR or surgical aortic valve replacement (SAVR) from 2010 to 2022. ARIMA models were used to study the impact of PARTNER trials and European guideline updates on TAVR use. Among 255,453 procedures, 109,739 were TAVR (N 2010 : 1,389; N 2022 : 16,770). No significant change in the proportion of TAVR was associated with PARTNER trials or European guideline updates (p ≥ 0.125). Median age and EuroSCORE II proxy were 83.0 years and 2.2 in TAVR group and 72.0 years and 1.4 in SAVR group. Approximately 60% of the TAVR and SAVR procedures were performed in public facilities. Latest valve generations replaced progressively earlier ones, with 62.5% being balloon-expandable. Mortality decreased over time in both groups, while length of stay and intensive care unit admissions decreased only in TAVR group. Conclusions This 13-year nationwide overview highlights the growing uptake of TAVR in France, likely driven by clinical practice and procedural innovation rather than guidelines. Further analyses will compare efficacy and safety between TAVR and SAVR.
VB5 modulates osteoclast metabolic reprogramming and suppresses differentiation by blocking PKM2 nuclear translocation
The co-occurrence of ingroup and outgroup prosociality requires cross-group partner choice
Markov modeling in R: Advanced method using a cost-effectiveness analysis
A Markov model is the kind of state transition model most widely used in Health Economic Evaluation (HEE) to analyse the efficiency of an intervention and support decision-making. However, it is has transition probabilities which remain constant over time, which limits its use for chronic diseases. Thus, to allow transition probabilities, rewards, or both, to vary over time, we use two types of methods: The first is “Implementing Time Dependency into Markov Transition Probabilities”, which allows probabilities to vary over time as measured from the start of the simulation. The second is “Relaxing the Markov Assumption”, by adding additional health states to the model, called tunnel states. In this tutorial, a case study on breast cancer is used to illustrate how to implement time dependence in a Markov model and how to conduct analyses of cost-effectiveness, probabilistic sensitivity, and the value of perfect information analyses with R.
Nutritional knowledge as a protective factor against eating disorders and a risk factor for orthorexic tendencies
An aquaglyceroporin governs cellular water and CO <sub>2</sub> conductance relevant for vesicular mineral formation in a marine calcifier
Many marine organisms generate biominerals by endocytotic uptake of seawater which is modified within calcifying cells to produce an amorphous mineral precursor required to form the mineralized shell or skeleton. In this process, water must be removed from the endocytotic vesicles and the cell to promote concentration of calcification substrates and production of a water-free mineral. Here, we demonstrate that in the sea urchin larva, an aquaglyceroporin (spAQP9) is involved in the cellular calcification process. spAQP9 is found exclusively in the calcifying primary mesenchyme cells (PMCs), and spAQP9 expression is increased during mineralization underlining its role in skeleton formation. Heterologous expression of sp AQP9 in Xenopus laevis oocytes demonstrated that this channel conducts water and carbon dioxide. The water conductance by spAQP9 is sensitive to phloretin with an IC 50 of ∼38 µM and treatment of larvae with phloretin or knock-down of spAQP9 impaired skeleton formation. Immunohistological analyses revealed localization of spAQP9 in vesicles with different subcellular distribution depending on the calcification activity of PMCs. Finally, we developed an in vivo assay to measure cellular and vesicular water permeability in PMCs and found a significant water permeability of the plasma membrane and membranes of calcium-rich vesicles. The results of this work highlight the importance of water transport mechanisms in the mineralization process. Here, aquaporins like spAQP9 represent key players that serve a dual function as a water and CO 2 conductance pathway and thereby can support ion concentration and carbon transport, two processes that are of fundamental importance to promote intracellular mineral precursor formation.
Vaccine management systems with a focus on cold chain management and delivery of immunization services in low- and middle-income countries: A scoping review
Objective The main objective of this scoping review is to examine the characteristics of vaccine management and delivery systems with a specific focus on cold chain management used for routine immunization in the LMICs, along with factors influencing these systems, challenges faced and the extent of digitization implemented. Methods A comprehensive literature search was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar for studies published between 2010 and February 2025. Our study selection, data charting, and synthesis followed methodological frameworks outlined by the Joanna Briggs Institute and PRISMA guidelines for Scoping Review. Result Outof 2451 identified studies, 16 eligible studies were included. The findings revealed diverse vaccine management system designs, including centralized and decentralized architecture, interoperable integrated models, and provisions for online and offline accessibility. Core features of these systems included longitudinal health records, automated inventory monitoring, and beneficiary engagement features including digital health cards. Implementation was influenced by global initiatives, project management teams and their capability, and challenges related to digitization. Factors impacting vaccine delivery included immunization sessions, stock management systems, distribution weaknesss, suboptimal practices, training gaps, and documentation. Digital transformations varied across countries, with Vietnam, Tanzania, and Zambia adopting electronic immunization registries, while India implemented the Electronic Vaccine Intelligence Network. The implementation of these digital logistics management information systems significantly improved vaccine management by reducing wastage, enhancing record-keeping, and optimizing supply chain efficiency. Conclusion To our knowledge, this scoping review is the first to provide empirical evidence on vaccine management and delivery systems and digitization in immunization in the LMICs. This review concludes that LMICs have been adapting various systems including electronic system, digitization, decentralisation of vaccine delivery, stock monitoring, individual tracking to improve immunization. Across countries, some have made notable progress, while others are at their initial stage of implementation. However, this review suggests further studies on integrated vaccine management systems and their impact for inter-country comparison.