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Tastes and retronasal odours evoke a shared flavour-specific neural code in the human insula

Nature Communications Putu Agus Khorisantono, Maria G. Veldhuizen, Janina Seubert Sep 12, 2025 DOI: 10.1038/s41467-025-63803-6

Abstract During food consumption, tastes combine with retronasal odours to form flavour, which leads to a link so robust that retronasal odours can elicit taste sensations without concurrent taste stimulation. However, the cortical integration of these parallel sensory signals remains unclear. Here, we combine a flavour-binding paradigm and functional neuroimaging to test whether retronasal odorants evoke encoding patterns in the insula similar to those of their paired tastants. Healthy participants attend a familiarisation session with congruent sweet and savoury flavours followed by two functional MRI (Magnetic Resonance Imaging) sessions where they separately receive the constituent tastants and odorants. Multivariate pattern analysis reveal classification of retronasal odours within the insula, exhibiting overlapping representations with their associated tastes, particularly in the ventral anterior insula. Additionally, we observe temporal drift in insular taste representations, paralleling findings in rodent gustatory cortex. These findings underscore the robust crossmodal influences of gustatory and retronasal olfactory processing that underpin the flavour percept.

The reference genome of the human diploid cell line RPE-1

Nature Communications Emilia Volpe, Alessio Colantoni, Luca Corda et al. Sep 12, 2025 DOI: 10.1038/s41467-025-62428-z

Meltwater ponding has an underestimated radiative effect on the surface of the Greenland Ice Sheet

Nature Communications Jonathan C. Ryan, Matthew G. Cooper, Sarah W. Cooley et al. Sep 12, 2025 DOI: 10.1038/s41467-025-62503-5

Asymmetric coordination enhances the synergy of Pt species dual active sites for efficient photocatalytic H2 evolution

Nature Communications Bo Li, Hongshun Zheng, Tong Zhou et al. Sep 12, 2025 DOI: 10.1038/s41467-025-63637-2

Heterogeneous, temporally consistent, and plastic brain development after preterm birth

Nature Communications Melissa Thalhammer, Jakob Seidlitz, Antonia Neubauer et al. Sep 12, 2025 DOI: 10.1038/s41467-025-63967-1

Abstract The current view of neurodevelopment after preterm birth presents a strong paradox: diverse neurocognitive outcomes suggest heterogeneous neurodevelopment, yet numerous brain imaging studies focusing on average dysmaturation imply largely uniform aberrations across individuals. Here we show both, spatially heterogeneous individual brain abnormality patterns but with consistent underlying biological mechanisms of injury and plasticity. Using cross-sectional structural magnetic resonance imaging data from preterm neonates and longitudinal data from preterm children and adults in a normative reference framework, we demonstrate that brain development after preterm birth is highly heterogeneous in both severity and patterns of deviations. Individual brain abnormality patterns are also consistent for their extent and location along the life course, associated with glial cell underpinnings, and plastic for influences of the early social environment. Our findings extend conventional views of preterm neurodevelopment, revealing a nuanced landscape of individual variation, with consistent commonalities between subjects. This integrated perspective implies more targeted theranostic intervention strategies, specifically integrating brain charts and imaging at birth, as well as social interventions during early development.

Role of c-Myc activating the transcription of PD-L1 in immune escape during benzene-induced malignant transformation of human lymphoblasts

PLoS ONE Qihao Huang, Biyan Ye, Zhongming Ye et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0332277

Benzene is a widely used industrial raw material. Benzene and its metabolite hydroquinone are believed to be related to the occurrence of benzene-related leukemia. Epidemiological studies have revealed the link between benzene exposure and blood system tumors, but the mechanism of benzene exposure and blood system tumor immune escape has not been fully confirmed. Experiments are divided into in vitro experiments and in vivo experiments. In the in vivo experimental part, we constructed an animal model of chronic benzene exposure and a C57BL/6 tumor-like animal model. Through qRT-PCR, Western blot and Tumor formation experiment in C57BL/6 mice, we verified that chronic benzene exposure caused malignant lesions in mice. In in vitro experiments, we built an in vitro malignant transformation model. Through molecular biology experiments 9/3/20259/3/20259/3/20259/3/2025such as CCK-8, soft agar cloning, and Transwell experiments were conducted to assess the malignant transformation potential of HQ19 and PBS19, cell vitality, malignant transformation potential and malignant migration ability were detected respectively. In order to study whether the benzene metabolite HQ activates c-Myc transcription activity, we used experiments such as double fluoresin enzyme reporting genes to confirm that c-Myc directly binds to PD-L1 promoter to drive its transcription. This study confirmed that in the process of HQ induced malignant transformation of human lymphocytes TK6, c-Myc regulates the molecular mechanism of PD-L1-mediated immune escape through transcription.

Integration of wearable devices and artificial intelligence in Alzheimer’s disease: A scoping review protocol

PLoS ONE Wenhao Qi, Yankai Shi, Shiying Shen et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0331129

The incidence of Alzheimer’s disease (AD) continues to rise, and predictive models combining artificial intelligence (AI) with wearable devices offer a new approach for its detection and diagnosis. Existing reviews remain focused on traditional biomarkers, making it necessary to supplement the evidence in this field, particularly given the rapid advancements in wearable and AI technologies. The scoping review protocol aims to systematically evaluate AI-based predictive models using wearable devices for AD, with a focus on their measurement outcomes and model development processes. The review will follow the Arksey and O’Malley framework and incorporate PRISMA-ScR guidelines. This study will search multiple databases, including Web of Science, Cochrane Library, and PubMed, covering relevant gray literature. The quality of the included studies will be rigorously assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST) and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) checklists. Two independent reviewers will conduct title and abstract screening, retrieve and assess full-text evidence sources, and extract data. The results will be narratively synthesized and presented in tables and figures. The knowledge gained from this review is expected to provide systematic evidence supporting AI-based predictive models that combine wearable devices for AD, potentially offering insights into model construction details such as data collection and external validation.

How do college coaches in the United States identify youth female and male soccer players?

PLoS ONE Matthew Andrew, Sam Barraclough, Andrew O. Triggs et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0331134

Talent identification (TI) in soccer is a complex and multifactorial process within the context of collegiate sport in the United States, where coaches must assess performance-ready athletes often under strict regulatory and resource constraints. Despite the critical role college coaches play in bridging youth to professional soccer, little is known about their evaluative priorities during recruitment. This study examined how soccer coaches from female and male NCAA Division I and II programs perceived the importance of various player attributes and scouting methods in the TI process. A total of 178 college soccer coaches completed a survey assessing perceptions across seven attribute categories (technical, physical, psychological, game intelligence, social, other, and coach-specific) and common scouting methods. Bootstrapped trimmed means, effect sizes, and inter-rater agreement (rwg) were used to analyse the coaches’ ratings of importance across attributes and to assess for differences in coach perceptions within the female and male programs. Results showed coaches across female and male programs rated technical proficiency, coachability, decision-making, and work rate as critically important. College-specific soccer knowledge was the most highly valued coach attribute, while live match observation was the most preferred scouting method. Sex-based differences were generally minimal, although emerged in perceptions of physical and social attributes, with coaches of female players placing greater emphasis on communication and agility. Results highlighted a shared prioritisation of technical and psychological qualities in college TI, with contextual differences influenced by sex and program structure. These insights support the development of more aligned and evidence-informed TI strategies in collegiate soccer environments.

Genome-wide identiffcation of the WRKY gene family in poplar and the positive role of PsnWRKY95 in response to cadmium stress

PLoS ONE Yuzhao Ma, Yiqi Liu, Fenglin Jia et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0332076

WRKY is a crucial transcription factor family in plants, participating in a variety of physiological processes and stress responses. In this study, we identified 102 WRKY genes from the poplar genome, randomly distributed on 18 chromosomes and one scaffold, and classified them into three subgroups based on phylogenetic analysis. Members of the same subgroup form similar structures due to their shared relatively conservative domains. All poplar WRKY proteins are hydrophilic, located in the cell nucleus, and form target relationships with a large number of miRNAs, with their promoter containing a large number of stress defense elements. The expansion of the poplar WRKY family mainly occurs through segmental duplication, and they also have abundant cross-species collinearity. Based on RNA-Seq, we identified 83 WRKYs significantly respond to cadmium (Cd) stress. Subsequently, we conducted a study on WRKY95, which was significantly up-regulated in the roots, stems, and leaves under Cd stress. Under cadmium toxicity, the plant height of PsnWRKY95-overexpressing plants increased by 16%−26% compared with the wild type (WT), the root length increased by 12%−27% compared with WT, the peroxidase (POD) activity was 28%−51% higher than that of WT, the chlorophyll content increased by 15%−29% compared with WT, the malondialdehyde (MDA) content decreased by 13%−32% compared with WT, and the electrical conductivity decreased by 9%−20% compared with WT, with the expression levels of POD and HMA1 in the overexpressing plants also being higher than those in WT. Results from yeast experiments demonstrated that PsnWRKY95 can improve Cd tolerance by specifically binding to cadmium (Cd) resistance element G-box, activating the reactive oxygen clearance ability and downstream target gene. This study comprehensively analyzes the basic data of WRKYs, identifying their response to Cd stress and specifically analyzes the stress-resistant function of PsnWRKY95, providing clues for understanding the molecular mechanism of WRKYs resistance to Cd.

Health-economic evaluation of statins versus lifestyle changes for cardiovascular disease prevention

PLoS ONE Afschin Gandjour Sep 12, 2025 DOI: 10.1371/journal.pone.0331176

Introduction The German Federal Ministry of Health aims to improve cardiovascular health by expanding statin eligibility. However, the shift in funding from lifestyle-based preventive programs to statins has raised concerns that existing prevention efforts could be undermined. This study assessed the cost-effectiveness of statins compared with lifestyle interventions for the prevention of cardiovascular disease (CVD) in Germany under constrained healthcare budgets. Methods A cost-effectiveness analysis was conducted using secondary data. Effectiveness data for statins were drawn from meta-analyses and systematic reviews, showing a 26% reduction in major cardiovascular events. Lifestyle intervention data were derived from the US Preventive Services Task Force (2020), reporting a relative risk of 0.80 for CVD events. A z-score test compared the effectiveness, while a Bayesian analysis assessed the probability of statins being more effective. Costs were analyzed from the perspective of German statutory health insurance (SHI) enrollees, including copayments and treatment monitoring expenses. Results The z-score of −1.26 (p = 0.207) indicated no statistically significant difference in the effectiveness of statins compared to lifestyle interventions. However, Bayesian analysis estimated an 89.7% probability that statins are more effective. Statins were generally cheaper, especially when preventive courses are repeated annually. Conclusions Statins likely offer higher cost-effectiveness than lifestyle changes, though the difference in benefits is not statistically significant. Concerns about reallocating funds from lifestyle programs to statins are somewhat mitigated by these findings.

ETS2 targets ZMYND11 to inhibit thyroid cancer progression via the mTOR signaling pathway

PLoS ONE Taipengfei Shu, Xinhua Wu, Chengqun Wei et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0328881

Background Despite advancements in thyroid cancer (THCA) treatment, the prognosis for advanced cases remains poor. Cellular senescence is crucial in tumor progression, with ETS2 emerging as a key regulator. However, the role of ETS2 and its interaction with ZMYND11 in THCA is unclear. Methods Differentially expressed genes (DEGs) connected with cellular senescence were determined from The Cancer Genome Atlas (TCGA)-THCA dataset. Functional analysis, prognostic risk model, and nomogram were then performed to identify ETS2 as a hub gene. The roles of ETS2 and ZMYND11 were explored using Western blotting (WB), co-immunoprecipitation (Co-IP), and quantitative real-time polymerase chain reaction (qRT-PCR). Effects of ETS2 overexpression and knockdown of ZMYND11 on apoptosis, cell proliferation, epithelial-mesenchymal transition (EMT), and mTOR signaling were evaluated. In vivo, a xenograft model was established using Cal-62 cells with or without ETS2 overexpression to assess tumor growth and protein expression. Results ETS2 was notably downregulated in THCA, and its low expression was connected to adverse prognosis. ETS2 overexpression inhibited THCA cell invasion, migration, proliferation, and induced apoptosis. ETS2 also regulated the expression of EMT markers, indicating its role in inhibiting THCA progression. Co-IP analysis showed that ETS2 interacted with ZMYND11. Knockdown of ZMYND11 attenuated the inhibitory effect of ETS2 on THCA cell behavior and mTOR pathway regulation. In vivo, ETS2 overexpression reduced tumor growth and increased ETS2 and ZMYND11 expression in xenograft tumors. Conclusion This study identified the cellular senescence gene ETS2 as a tumor suppressor in THCA, which interacts with ZMYND11 to regulate THCA tumor progression through the mTOR pathway, thereby inhibiting cell senescence. Targeting the ETS2-ZMYND1 axis may provide new therapeutic strategies and prognostic biomarkers for THCA.

Sun protection behavior beliefs among adults living in rural United States: A qualitative study in Minnesota

PLoS ONE Patricia Jewett, Matia Solomon, Katherine Brown et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0331685

Although skin cancers are considered mostly preventable, more people in the US are diagnosed with skin cancer than all other cancers combined. Sun safety recommendations include wearing sun-protective clothing, a wide-brimmed hat, seeking shade, and using sunscreen. Some evidence exists that sun risk behaviors and skin cancer rates are more frequent among rural than urban US populations, raising questions about underlying factors. We conducted a belief elicitation survey on these four sun protection behaviors among 278 adults (aged 18–60 years) living in rural Minnesota, a state with high sunburn rates and UV-attributable melanoma cases. These qualitative data were analyzed using content analysis, and the identified codes ranked by frequency. Almost all participants emphasized that spending time outside was important to them. The most frequently reported sun protection behaviors were wearing sunscreen and protective clothing. The primary outcomes were obtained from open-ended questions on outcome, normative, and control beliefs associated with each sun protection behavior. While many different beliefs were mentioned, reducing sunburn and skin cancer risk were commonly reported across all behaviors. Beliefs about negative aspects of each behavior (e.g., interference with being physically active or doing work outside, greasy/sticky sunscreen, not getting a suntan, overheating in long clothes or when wearing hats, hats that blow off easily) typically outnumbered positive aspects (e.g., protective behaviors enabling being outside, staying cool in shade, reduced skin aging). The majority of participants believed that most people would approve of all protection behaviors, but many thought that age was a factor for behavior adoption, with young people typically thought to engage less in protective behaviors. Some commonly reported negative aspects of sun protective behaviors were related to activities more common in rural populations, such as working outside. This suggests that rural sun protection promotion may include structural interventions to make sun protection easy, convenient, and accessible without impeding rural lifestyles.

The impact of outdoor walking interventions on frailty among older adults with mobility limitations: Findings from the Getting Older Adults Outdoors (GO-OUT) study

PLoS ONE Tai-Te Su, Ruth Barclay, Rahim Moineddin et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0323923

Objective Diverse strategies are needed to reduce frailty. This study evaluated the effects of two behavioural interventions targeting outdoor walking on reducing the level of frailty among community-dwelling older adults with mobility limitations. Methods Data from two participant cohorts of the Getting Older Adults Outdoors (GO-OUT) study were analyzed. After baseline evaluations, 190 participants were invited to a one-day educational workshop and were then randomized to either a 10-week supervised outdoor walk group (n = 98) or a 10-week telephone weekly reminders group (n = 92). Frailty was assessed using Fried’s frailty index at 0, 3, and 5.5 months. Mixed-effects linear and ordinal regression models were used to evaluate change in frailty score and phenotype over time after accounting for age, sex, study site, participation on own or with a partner, and cohort. Results At baseline, participant mean age was 74.5 ± 7.1 years; 73% were female, 7% were frail, and 59% were pre-frail. Total frailty scores decreased, on average, by 0.13 points ( b  = –0.13, 95% CI: –0.26 to –0.01; p  = .036) across all participants from 0 to 3 months (immediately post-intervention). Participants were 55% less likely to progress to more severe frailty phenotypes at 3 months compared to baseline (OR=0.45; 95% CI: 0.25 to 0.81; p  = .008). No significant between-group differences or long-term effects were observed. Conclusions A short-term reduction in frailty was observed in older adults with mobility limitations following participation in behavioural interventions aimed at improving outdoor walking; neither intervention was superior. Supervised outdoor walk group and telephone weekly reminder interventions to increase outdoor walking may have the potential to mitigate frailty in older adults with mobility limitations.

It’s not difficulty that matters, but strategy: Perceived stressor, functional and dysfunctional coping strategies in ultra-trails of extreme duration

PLoS ONE Pietro Trabucchi, Barbara Pellegrini, Aldo Savoldelli et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0332058

To date, no studies have proposed specific taxonomies of stressors and coping strategies used to manage them by ultra trail runners in races longer than 200 miles, with existing research focusing on significantly shorter distances an then on challenges that could be of a different nature. The aim of this study was to fill this gap by developing specific taxonomies that would group both the stressors encountered and the coping strategies into distinct conceptual categories. Furthermore, to observe in a real competition if these taxonomies allows the evaluation of the coping strategies used by athletes. Two Focus Groups composed of experts on the topic proposed provisional classifications, which were analysed using Applied Thematic Analysis. Three distinct Draft Taxonomies were identified: typical stressors, functional and dysfunctional coping strategies used by athletes during competitions. A critical comparison between the provisional taxonomies and literature led to the development of three definitive taxonomies. In a second phase, to verify whether the taxonomies reflected the real experiences of runners, seven participants in a 280-mile race were interviewed daily during the event. Their responses regarding the stressors and the strategies they had implemented to deal with them were recorded. Expert panelists categorized the transcribed responses according to the proposed taxonomies. The concordance of the judgments, verified with the Fleiss K, was considered a measure of the taxonomies’ ability to capture real experiences. Results confirmed substantial agreement between the raters regarding both the stressors (K = 0.711, p < 0.001) and the coping strategies (K = 0.73, p < 0.001). The analysis of the proportion between the use of functional and dysfunctional strategies proved to be high (between 0.66 and 1) among athletes who completed more than 50% of the race. The taxonomies were found to effectively described athletes’ race experiences, revealing context-specific coping strategies likely developed through years of practice.

Research on the influence of the morphology of coarse aggregates from Reclaimed Asphalt Pavement (RAP) on the mechanical properties of asphalt concrete based on finite element modeling

PLoS ONE Nan Ru, Yu Zhao, Zhaoting Liu et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0323128

Using recycled coarse aggregates (RCA) to prepare asphalt mixtures can reduce the consumption of natural sand and gravel resources and solve the environmental pollution problem caused by waste asphalt concrete materials. To promote the widespread application of RCA, research has been conducted on fully recycled asphalt concrete (FRCAC). The ABAQUS finite – element software was used, and a random aggregate placement algorithm for RCA was implemented by writing the built – in scripting language Python to generate digital specimens. After obtaining the material parameters through indoor tests, the digital specimens were analyzed. Four aggregate characteristic parameters, namely aspect ratio, shape parameter, roundness ratio, and angularity, were selected to further describe the relationship between the external features of RCA and the mechanical properties of asphalt concrete. The results show that: (1) As the irregularity of the RCA’s external shape increases, the ultimate failure load of the specimens shows an upward trend. (2) When the aspect ratio reaches 1.70 to 1.75, the shape parameter reaches 0.70 to 0.75, the roundness ratio is between 0.84 to 0.82, and the angularity reaches 0.76 to 0.74, the ultimate failure load of the specimens shows a downward trend. (3) The finite-element modeling algorithm can well reflect the morphology of coarse aggregates and accurately characterize the influence of aggregate morphology on the mechanical properties of asphalt mixtures.

Evaluation of collector spacing, positioning, and nozzle selection methods on water distribution uniformity in center pivots

PLoS ONE Lucas Maltoni Andrade, Rubens Alves de Oliveira, Fernando França da Cunha et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0331122

Proper design and periodic evaluation of center pivot irrigation systems are essential for ensuring uniform water distribution and improving water use efficiency in irrigated agriculture. This study assessed the impact of collector spacing and sampling methods, including a single-level collector line and combinations of multiple lines at different irrigated locations, on water distribution uniformity. Additionally, strategies for selecting emitter nozzles were analyzed. Uniformity assessments were conducted on two center pivots (P180 and P360) using collectors spaced at 1 m, with simulated spacings of up to 12 m by omitting intermediate readings. Collector lines were placed perpendicular to the pivot’s movement at 50% regulation and were evaluated three times. Data were analyzed individually for each line position and in groups, following layout recommendations from the literature. The mean water depth (LM), weighted mean depth (LW), and modified Christiansen’s uniformity coefficient (CUCHH) were used as evaluation metrics. Flow rate measurements were performed, with three repetitions per nozzle number. Nozzle selection considered the required flow rate and nozzle diameter for both constant and doubled spacing between emitters in the first two spans. Measured flow rates resulted in higher simulated water depths and lower CUCHH values compared to simulated reference flow rates. However, the average field CUCHH exceeded 90% for both pivots, being classified as excellent. Evaluation methods combining different collector line positions showed no significant differences between means, nor did the combined effect of collector spacing and single-line positioning. No significant differences were found between collector spacings alone. However, collector line positioning influenced results, with P180 showing differences in LW and P360 in LM, LW, and CUCHH. Estimated evaporation and wind drift losses were 14.21% for P360 and 13.49% for P180. The evaluated nozzle selection combinations showed a theoretical CUCHH higher than the simulated values based on the original nozzle listing for both pivots.

Hormonal contraceptives and body composition by use of stable isotope dilution techniques among women of reproductive age in Nyeri County, Kenya

PLoS ONE Purity Chepkorir Lang'at, Dorcus Mbithe David-Kigaru, Zipporah W. Ndung'u et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0332299

Background Hormonal contraceptives are widely used by women of reproductive age (WRA) globally, yet their impact on body composition remains poorly understood, particularly in low-resource settings. This study aimed to assess the effects of hormonal contraceptives on body composition among WRA in Nyeri County, Kenya, using Stable Isotope Dilution Techniques (SIDT). Methods A two-stage cross-sectional analytical study was conducted among 119 women of reproductive age (WRA) aged 18–49 years. However, five participants were excluded from the final analysis. Participants were purposively grouped into hormonal contraceptive users (n = 41), non-hormonal contraceptive users (n = 37), and not on contraceptive (n = 36). After accounting for loss to follow-up, 114 were analysed at baseline and 104 at endline. Contraceptive types included injectables (DMPA), oral pills, and implants (hormonal); and copper IUDs and condoms (non-hormonal). A mid-point (3-month) assessment was conducted for compliance, with the primary body composition outcome measured at six months. Demographic and socioeconomic data were collected using validated structured questionnaires. Body composition was assessed at baseline and six months later using SIDT, with saliva samples analysed to determine total body water (TBW), fat-free mass (FFM), and fat mass (FM). Physical activity (GPAQ) and dietary diversity (WDDS) were measured to control for confounding factors. Logistic regression analysis was adjusted for physical activity, and dietary diversity. Results Hormonal contraceptive users showed a significant increase in body fat percentage from 35.3 ± 9.3% to 41.7 ± 10.6% (p = 0.039) and a reduction in %TBW (47.4 ± 6.8% to 42.3 ± 7.8%, p = 0.048). Non-hormonal and non-contraceptive users showed no significant changes. Regression analysis confirmed hormonal contraceptive use was a significant predictor of body fat percentage (Exp(β) = 0.31, p = 0.026), independent of other factors. Conclusion Hormonal contraceptive use is associated with increased body fat and reduced total body water among WRA in Nyeri County. These changes, independent of physical activity and diet, suggest a direct metabolic effect. Regular body composition monitoring and tailored nutritional guidance are recommended for women using hormonal contraceptives.

Wound healing effects of 80% methanol and solvent fractions of the leaf of Cordia Africana Lam: (Boraginaceae) against wound models in mice

PLoS ONE Jemal Abdela, Fuad Adem, Ahmedmenewer Abdu et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0331377

Background Chronic wounds present a major health challenge, and traditional remedies are frequently employed in developing nations for wound treatment. This study sought to assess the safety and effectiveness of various solvent extracts from Cordia africana using excision and incision wound models in mice. Methods The dried, coarsely ground 500 g of plant leaves were separately macerated three times with 80% methanol, absolute methanol, chloroform, and aqueous water. Acute dermal toxicity was assessed by applying 2000 mg/kg of the 10% w/w of the solvent extracts. In both wound models, animals were randomly divided into four groups of five mice each. Group I received a simple ointment and served as the negative control. Group IV was treated with nitrofurazone (0.2%) ointment as the positive control. Groups II and III were treated with 5% w/w and 10% w/w ointments of the solvent extracts, respectively. Results The acute dermal toxicity studies demonstrated that the plant leaf extracts are safe, as there were no signs of toxicity observed. In the excision wound model, the application of 5% and 10% ointments of the 80% methanol extract resulted in significant (p < 0.05) wound contraction compared to the negative control group, starting from day 13 and day 5, respectively. Similarly, 10% ointments of both absolute methanol and chloroform extracts significantly (p < 0.05) reduced wound size starting from day 7. Furthermore, the time required for complete epithelization was significantly shorter (p < 0.05) for the 80% methanol, chloroform, and absolute methanol extracts compared to the negative control. The chloroform fraction and 10% ointment of the 80% methanol extracts also significantly increased hydroxylproline content. The 5% and 10% chloroform extract ointments (66.02% and 72.20%, respectively) and the 10% ointment with an 80% methanol extract (55.49%) significantly improved the tensile strength of the mice skin (p < 0.05) compared to the group treated with a simple ointment (1.6%). Conclusion The study revealed that Cordia africana leaf extracts possess significant wound-healing properties, supporting its traditional medicinal use. It was found that using less polar solvents is more effective in extracting components with enhanced wound-healing effects.

The admissibility of digital evidence from open-source forensic tools: Development of a framework for legal acceptance

PLoS ONE Isa Ismail, Khairul Akram Zainol Ariffin Sep 12, 2025 DOI: 10.1371/journal.pone.0331683

The proliferation of cybercriminal activities from 2023 to 2025 has highlighted the critical role of digital forensics in legal proceedings; however, resource constraints often limit access to effective investigative capabilities. Despite the technical adequacy of open-source digital forensic tools, courts typically favor commercially validated solutions because of the absence of standardized validation frameworks for open-source alternatives, creating unnecessary financial barriers to high-quality forensic investigations. This study aims to validate and enhance the conceptual open-source digital forensic framework developed by Ismail et al. (2024) to ensure the legal admissibility of evidence acquired through open-source tools. Through a rigorous experimental methodology utilizing controlled testing environments, we conducted comparative analyses between commercial tools (FTK and Forensic MagiCube) and open-source alternatives (Autopsy and ProDiscover Basic) across three distinct test scenarios: preservation and collection of original data, recovery of deleted files through data carving, and targeted artifact searching. Each experiment was performed in triplicate to establish repeatability metrics, with error rates calculated by comparing the acquired artifacts with control references. Our findings demonstrate that properly validated open-source tools consistently produce reliable and repeatable results with verifiable integrity comparable to their commercial counterparts. The enhanced three-phase framework integrating basic forensic processes, result validation, and digital forensic readiness to satisfy Daubert Standard requirements while providing practitioners with a methodologically sound approach. This study contributes significantly to digital forensics by democratizing access to forensically sound investigative capabilities without compromising legal admissibility requirements, ultimately benefiting resource-constrained organizations while maintaining the evidentiary standards necessary for judicial acceptance.

Self-guided versus facilitator-guided debriefing in immersive virtual reality simulation: Protocol for a randomized controlled non-inferiority trial assessing teamwork skills in medical students

PLoS ONE Amalie Middelboe Sohlin, Anja Poulsen, Ida Madeline Hoffmann et al. Sep 12, 2025 DOI: 10.1371/journal.pone.0332309

Simulation-based medical education has been shown to be more effective but also logistically demanding and costly compared to other educational strategies in developing medical skills. Immersive virtual reality is an emerging technology enabling learners to train without a facilitator through computer-generated feedback, offering the potential for increased flexibility in the timing and location of the training and reduced costs. However, little is known about whether immersive virtual reality simulation yields similar results with and without a facilitator. The aim of this study is to compare the effects of self-guided compared to facilitator-guided debriefing for immersive virtual reality simulation-based pediatric emergency team training. We will conduct a randomized, controlled, single-blinded non-inferiority study with a parallel group, pretest-post-test design. 88 medical students (44 teams) will be randomized to undergo immersive virtual reality simulation-based pediatric emergency team training with either self-guided or facilitator-guided debriefing. We will assess the teams before and after the virtual reality intervention in a mannequin-based simulation. The mannequin-based simulation will be videorecorded, and two independent raters, blinded to group allocation, will assess the recordings using validated scales measuring teamwork skills (primary outcome), ABCDE adherence, and time to critical actions. We will further collect data on perceptions of debriefing quality, motivation, workload, usability, and cybersickness. To account for repeated measures and clustering within teams, we will apply a linear mixed model for data analysis. This study aims to provide insight into the effects of self-guided versus facilitator-guided debriefing in immersive virtual reality simulation, with implications for the future development and implementation of immersive virtual reality simulation in medical education. We have registered the trial on ClinicalTrials.gov (identifier: NCT06956833).