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  • PLOS One

    https://journals.plos.org/plosone/

    Correction: Targeted modulation of MMP9 and GRP78 via molecular interaction and in silico profiling of Curcuma caesia rhizome metabolites: A computational drug discovery approach for cancer therapy

    by Mahek Desai, Soham Bhattacharya, Saurabhkumar Mehta, Kaushiki Joshi, Mitesh B. Solanki, Trilok Akhani, Iva Viehmannová, Eloy Fernández Cusimamani


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0339069

    Correction: Additional outreach effort of providing an opportunity to obtain a kit for fecal immunochemical test during the general health check-up to improve colorectal cancer screening rate in Japan: A longitudinal study

    by The PLOS One Staff


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0339049

    Correction: Informal care in different European care systems: Effects of caregiving on mental health over time

    by Leonie Börner, Ingo W. K. Kolodziej, Jürgen Wasem, Carina Abels


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0339047

    Correction: The impacts of product characteristics and regulatory environment on smokers’ preferences for tobacco and alcohol: Evidence from a volumetric choice experiment

    by Shaoying Ma, Ce Shang, Vuong V. Do, Jidong Huang, Terry F. Pechacek, Scott R Weaver


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0339046

    Correction: Translation, cross-cultural adaptation and psychometric properties of the Arabic version of the Fremantle Knee Awareness Questionnaire in people with knee osteoarthritis

    by Mohammad Madi, Hayat Hamzeh, Sumayeh Abujaber, Ibrahim Altubasi


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0339036

    Development of a competition assay to assess the in vitro fitness of dengue virus serotypes using an optimized serotype-specific qRT-PCR

    by Anne-Fleur Griffon, Loeïza Rault, Clément Tanvet, Etienne Simon-Lorière, Myrielle Dupont-Rouzeyrol, Catherine Inizan

    Background

    Comparing the in vitro fitness of dengue virus (DENV) isolates is a pivotal approach to assess the contribution of DENV strains’ replicative fitness to epidemiological contexts, including serotype replacements. Competition assays are the gold standard to compare the in vitro replicative fitness of viral strains. Implementing competition assays between DENV serotypes requires an experimental setup and an appropriate read-out to quantify the viral progeny of strains belonging to different serotypes.

    Methods

    In the current study, we optimized an existing serotyping qRT-PCR by adapting primer/probe design and multiplexing the serotype-specific qRT-PCR reactions, allowing to accurately detect and quantify all four DENV serotypes. We next developed an in vitro competition assay to compare the replicative fitness of two DENV serotypes in the human hepatic cell line HuH7.

    Findings

    The qRT-PCR was specific, and had a limit of detection below 7.52, 1.19, 3.48 and 1.36 genome copies/µL, an efficiency of 1.993, 1.975, 1.902, 1.898 and a linearity (R²) of 0.99975, 0.99975, 0.99850, 0.99965 for DENV-1, −2, −3 and −4, respectively. Challenge of this multiplex serotype-specific qRT-PCR on mixes of viral supernatants containing known concentrations of strains from two serotypes evidenced an accurate quantification of the amount of genome copies of each serotype. Quantification of the viral progeny of each serotype in the inoculum and the supernatant of competition assays using the serotype-specific multiplex qRT-PCR unveiled an enrichment of the supernatant in DENV-1 genome copies, uncovering the enhanced replicative fitness of this DENV-1 isolate.

    Conclusions

    This optimized qRT-PCR combined with a relevant cellular model allowed to accurately quantify the viral progeny of two DENV strains belonging to two different serotypes in a competition assay, allowing to determine which strain had a replicative advantage. This reliable experimental setup is adaptable to the comparative study of the replicative fitness of any DENV serotypes.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0339033

    Comparison of outcomes between minimally invasive percutaneous bunnell suture and traditional open modified Kessler technique for acute closed achilles tendon rupture: A single-center cohort study

    by Zihang Zhao, Xiang Zhang, Xi Hou, Zihan Liu, Zhiyong Hou, Lianxin Song, Ruipeng Zhang

    Percutaneous Bunnell repair and open modified Kessler repair remain debated options for acute Achilles tendon rupture (AATR). We retrospectively compared a minimally invasive percutaneous Bunnell technique (Group A) with an open modified Kessler repair (Group B) within a standardized early functional rehabilitation (EFR) protocol at a single center. Fifty-five adults with closed AATR treated between January 2021 and December 2022 were analyzed (Group A, n = 25; Group B, n = 30). Between-group comparisons used Welch t tests for continuous variables and χ² or Fisher exact tests for categorical variables; American Orthopaedic Foot & Ankle Society (AOFAS) and Achilles Tendon Total Rupture Score (ATRS) were assessed at 12 and 24 weeks, with Holm adjustment applied within each scale. Compared with Group B, Group A had shorter operative time (56.6 ± 15.1 vs 68.2 ± 23.2 minutes; mean difference −11.6; 95% CI −22.05 to −1.15; P = 0.030), less intraoperative blood loss (28.4 ± 8.4 vs 74.7 ± 19.4 mL; −46.3; 95% CI −54.22 to −38.38; P < 0.001), and a shorter length of stay (4.8 ± 2.0 vs 6.6 ± 2.9 days; −1.8; 95% CI −3.13 to −0.47; P = 0.009). At 12 weeks, AOFAS favored Group A (+1.36; 95% CI + 0.19 to +2.53; P = 0.047) and ATRS also favored Group A (+1.73; 95% CI + 0.48 to +2.98; P = 0.008). At 24 weeks, AOFAS was not different (+0.51; 95% CI −0.49 to +1.51; P = 0.312), whereas ATRS remained higher in Group A (+2.17; 95% CI + 0.88 to +3.46; P = 0.003). Overall complications were 12.0% vs 26.7% (risk difference −14.7%; 95% CI −34.10 to +7.20; P = 0.310); no sural nerve injuries occurred. Within an EFR framework, percutaneous Bunnell repair provided superior perioperative efficiency with comparable safety and modest, sub-MCID functional advantages, supporting confirmation in larger prospective studies.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0339026

    Biopsychosocial factors associated with symptom severity in the overlap of non-erosive reflux disease and epigastric pain syndrome: A multicenter cross-sectional study

    by Mi Lv, Hui Che, Jiayan Hu, Wenxi Yu, Zhaoxia Liu, Xiaolin Zhou, Binduo Zhou, Jinyi Xie, Fengyun Wang

    Background

    The overlap between non-erosive reflux disease (NERD) and epigastric pain syndrome (EPS, a subtype of functional dyspepsia) is common, yet its associated factors remain poorly defined. We aimed to identify factors associated with symptom severity in NERD-EPS overlap, focusing on psychosocial and somatic factors.

    Methods

    In this multicenter cross-sectional study, 800 patients meeting Rome IV criteria for NERD-EPS overlap were enrolled. Standardized questionnaires assessed gastrointestinal symptoms (GSRS), somatic symptoms (PHQ-15), anxiety/depression (PHQ-4), and sleep quality (SRSS). Multivariable regression models identified factors independently associated with GSRS scores, adjusted for demographics and clinical covariates. Interaction terms were tested to assess whether the association between one factor and GSRS scores varied across different levels of another factor.

    Results

    Of the 800 patients, 67% were female, and the mean age was (44.50 ± 14.43) years. 67% had mild or more sleep problems, and 47% had anxiety or depression. Somatic symptoms (PHQ-15) showed the strongest association with GSRS scores (β = 0.617, P < 0.001), followed by poor sleep quality (SRSS; β = 0.115, P < 0.001) and anxiety/depression (PHQ-4; β = 0.069, P = 0.026). Urban residence (β = 0.071) and mixed labor type (β = −0.066) were also independently associated with symptom burden.

    Conclusion

    Somatic symptoms, psychological distress, and sleep disturbances were the factors most strongly associated with symptom severity in NERD-EPS overlap, with additional contributions from younger age, male sex, and urban residence. Our findings advocate for integrated biopsychosocial interventions to alleviate symptom burden in this population.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338971

    Correction: Associations between age at natural menopause and risk of hypothyroidism among postmenopausal women from the Canadian Longitudinal Study on Aging (CLSA)

    by The PLOS One Staff


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338845

    Optimizing vitamin A supplementation: A comparative cost-effectiveness analysis of routine distribution strategies in northern Côte d’Ivoire

    by Melissa M. Baker, Lyonel Nerolin Doffou Assalé, David Doledec, Romance Dissieka, Ahmenan Claude Liliane Konan, Agnes Helen Epse Assagou Mobio, Koffi Landry Kouadio, Oka René Kouamé, Ama Emilienne Yao, Hubert Zirimwabagabo

    Background

    While recent data on vitamin A deficiency (VAD) prevalence is lacking, the 2004 Côte d’Ivoire Nutrition and Mortality Survey reported that 26.7% of children aged 6–59 months were affected by VAD, and approximately 60% were at risk. Since 2016, the government has transitioned from mass campaigns to routine vitamin A supplementation (VAS) delivery integrated into health services. However, evidence on the cost-effectiveness of the routine distribution approaches is limited. This study evaluated the cost, coverage, and cost-effectiveness of three routine VAS delivery strategies across two health districts in northern Côte d’Ivoire.

    Methods

    A mixed-methods study evaluated three routine VAS delivery strategies – routine-fixed, advanced community-based, and catch-up – across two health districts, Ferkessédougou and Niakaramadougou, in northern Côte d’Ivoire. The quantitative cost data were collected via a structured tool covering six cost categories: planning, procurement, training, social mobilization, distribution, and supervision. VAS coverage was assessed through a post-event coverage survey (PECS) via a two-stage cluster sampling methodology. A cost-effectiveness analysis determined the cost per child supplemented, the cost per DALY averted, and a sensitivity analysis tested the robustness of the findings under different cost scenarios.

    Results

    The total program cost for July-December 2023 was 25.5 million FCFA, with personnel costs comprising over 70% of expenditures. In Ferkessédougou, the routine advanced community-based strategy was the most cost-effective, at 458 FCFA per child in rural areas (versus 596 FCFA for the routine-fixed facility-based approach in the same area). In Niakaramadougou, the December catch-up was more cost-effective in rural areas (606 FCFA per child) than the routine-fixed approach (714 FCFA). Across both districts combined, the routine-fixed strategy averaged roughly 651 FCFA per child supplemented, and the cost per DALY averted ranged from 30,093 FCFA (advanced strategy in Ferkessédougou) to 89,550 FCFA (catch-up Jul 2023 in Niakaramadougou) – all below Côte d’Ivoire’s cost-effectiveness threshold (0.5 x GDP per capita; approximately USD 1,265).

    Conclusion

    All three strategies were cost-effective, though the advanced community-based strategy achieved the best balance of reach and efficiency. Scaling advanced strategies within health system constraints may enhance sustainability and coverage in low-resource settings.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338784

    Editorial Note: Measurement and driving factors of carbon productivity in China’s provinces: From the perspective of embodied carbon emissions

    by The PLOS One Editors


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338756

    Expression of Concern: Governance and competitiveness evaluation of China’s financial asset management corporations

    by The PLOS One Editors


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338753

    Is price associated with the quality of medicines? Evidence from active pharmaceutical ingredient testing in Nigeria

    by Marie Chantel Montás, Chimezie Anyakora, Elisa Maria Maffioli

    Determining the quality of medicines remains a challenge, particularly in low- and middle-income countries, where regulatory oversight and enforcement vary, and resources and infrastructure for quality testing are often constrained. In these settings, price is often used as a proxy for higher-quality medicines, yet empirical evidence supporting this assumption remains scarce. We conducted a mystery shopper survey in over 1,200 retail pharmacies across urban and rural areas in the six geopolitical zones of Nigeria, purchasing one drug sample from a list of twenty branded medicines, including analgesics, antimalarials, antibiotics, antihypertensives, and multivitamins. A sub-sample of the purchased medicines (N = 246) was tested for quality, defined as passing a laboratory test using High-Performance Liquid Chromatography (HPLC) to measure the Active Pharmaceutical Ingredient (API) content of each medicine. Using probit regressions, we examined the extent to which price is associated with quality, controlling for observable pharmacy and drug sample characteristics. A 1% increase in price is associated with a 16.7 percentage point increase in the probability of passing the laboratory test, conditional on other factors. Receiver Operating Characteristic (ROC) analysis shows strong out-of-sample classification performance, with an Area Under the Curve (AUC) of 0.82 for the price-only model, indicating that price alone explains much of the variation in quality. Other results show that medicines organized by brand and displaying visible expiration dates may signal higher quality, while the presence of other observable characteristics (e.g., packaging, storage, display) shows more counterintuitive associations with drug quality in this context. Stratified analyses show that the association between price and quality is particularly strong for analgesics and antibiotics. These findings suggest that price appears to be a reliable signal of medicine quality, whereas other characteristics of pharmacies and drug samples provide weaker and less consistent indicators. This underscores the need for stronger regulatory oversight, greater market transparency, and targeted consumer education to promote safer access to quality medicines.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338739

    Cyclodextrin reduces cholesterol crystal uptake by circulating monocytes in patients undergoing coronary angiography

    by Nikola Lübbering, Alexander Krogmann, Felix Jansen, Eicke Latz, Georg Nickenig, Sebastian Zimmer

    Background

    Atherosclerosis is a chronic inflammatory disease driven by endothelial dysfunction, cholesterol accumulation, and immune activation leading to thrombosis and vascular stenosis. While LDL-lowering therapies are firmly established, targeting the underlying inflammation is still an emerging strategy. Cholesterol crystals (CC) contribute to inflammation by activating the NLRP3 inflammasome in monocytes and promoting disease progression. Cyclodextrin (CD), an FDA-approved drug carrier, has shown atheroprotective effects by enhancing cholesterol metabolism and reducing inflammation in preclinical models. This study investigated whether CC-uptake in human monocytes, a prerequisite for inflammasome activation, is also influenced by CD pretreatment.

    Methods

    Human peripheral mononuclear cells were isolated from whole blood samples provided by 76 patients undergoing coronary angiography at the University Hospital Bonn between November 2017 and February 2018. After separation, peripheral mononuclear cells were stimulated with 2-Hydroxypropyl-γ-Cyclodextrin and CC. CC-uptake by monocytes was analyzed using flow cytometry.

    Results

    CC-uptake by monocytes varied greatly between patients (8–37%), with lower uptake observed in patients with elevated leukocytes (p = 0.0058) and diabetes mellitus (p = 0.0448). CD-pretreatment significantly reduced CC-uptake (20.1% ± 0.8% vs. 15.0% ± 0.6%, p < 0.0001). Interindividual variability in CD response (CCΔCD) was noted; 40 patients exhibited a significant reduction in CC-uptake, while nine showed an increase. Patients with coronary artery disease (CAD) (p = 0.0316), requirement for percutaneous coronary intervention (PCI) (p = 0.0030), and elevated leucocyte levels (p = 0.0135) had lower CCΔCD, suggesting a link between systemic inflammation and attenuated CD efficacy.

    Conclusion

    We demonstrated that CD significantly reduced CC-uptake in patients undergoing coronary angiography, which supports its role in inhibiting CC-phagocytosis and promoting cholesterol efflux. Interestingly, patient response to CD varied, with those exhibiting greater systemic inflammation or CAD showing a less pronounced reduction in CC-uptake. Our findings provide insight into the atheroprotective mechanisms of CD and suggest its potential utility in evaluating individual cardiovascular risk and monitoring CD-based therapeutic interventions in humans.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338635

    A mixed-methods study to explore the modifiable aspects of treatment burden in Parkinson’s disease and develop recommendations for improvement

    by Qian Yue Tan, Kinda Ibrahim, Helen C. Roberts, Khaled Amar, Simon D.S. Fraser

    Background

    People with Parkinson’s (PwP) and their caregivers have to manage multiple daily healthcare tasks (treatment burden). This can be challenging and may lead to poor health outcomes.

    Objective

    To assess the extent of treatment burden in Parkinson’s disease(PD), identify key modifiable factors, and develop recommendations to improve treatment burden.

    Methods

    A mixed-methods study was conducted consisting of: 1) a UK-wide cross-sectional survey for PwP and caregivers using the Multimorbidity Treatment Burden Questionnaire (MTBQ) to measure treatment burden levels and associated factors and 2) focus groups with key stakeholders to discuss survey findings and develop recommendations.

    Results

    160 PwP (mean age = 68 years) and 30 caregivers (mean age = 69 years) completed the surveys. High treatment burden was reported by 21% (N = 34) of PwP and 50% (N = 15) of caregivers using the MTBQ. Amongst PwP, higher treatment burden was significantly associated with advancing PD severity, frailty, a higher number of non-motor symptoms, and more frequent medication timings (>3 times/day). Caregivers reporting higher treatment burden were more likely to care for someone with memory issues, had lower mental well-being scores and higher caregiver burden. Three online focus groups involved 11 participants (3 PwP, 1 caregiver and 7 healthcare professionals) recruited from the South of England. Recommendations to reduce treatment burden that were discussed in the focus groups include improving communication. clear expectation setting, and better signposting from healthcare professionals, increasing education and awareness of PD complexity, flexibility of appointment structures, increasing access to healthcare professionals, and embracing the supportive role of technology.

    Conclusions

    Treatment burden is common amongst PwP and caregivers and could be identified in clinical practice using the MTBQ. There is a need for change at individual provider and system levels to recognise and minimise treatment burden to improve health outcomes in PD.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338620

    Decentralized trust optimization in VANETs: A blockchain-driven hybrid PoS-PBFT architecture for enhanced security and energy-efficient communication

    by Asad Ullah, Zia Ullah, Sanam Shahla Rizvi, Ibrar Ali Shah, Se Jin Kwon

    Vehicular Ad Hoc Networks (VANETs) are essential for the success of Intelligent Transportation Systems (ITS), providing real-time communication between vehicles and infrastructure. However, the highly dynamic and decentralized nature of VANETs introduces significant challenges in ensuring trust and security across the network, including security threats, communication overhead, and energy inefficiencies. This paper presents a novel blockchain-based trust management framework that addresses these issues by incorporating lightweight consensus mechanisms, optimized data propagation strategies, and energy-aware protocols. Our approach reduces communication overhead by selectively propagating trust updates, leading to a 35% decrease in overall network traffic compared to traditional broadcast-based systems. In terms of trust accuracy, our model achieves over 95% accuracy in detecting malicious nodes, significantly outperforming existing solutions. The proposed system demonstrates the identification and penalization of malicious behaviors such as Sybil attacks and false reporting with a 25% improvement in detection rate, while maintaining low latency (an average reduction of 30% compared to PoW-based systems) and efficient energy consumption, reducing energy use by up to 40%. The proposed model also incorporates a hybrid Proof of Stake (PoS) and Practical Byzantine Fault Tolerance (PBFT) consensus mechanism, which further enhances its scalability and fault tolerance. Simulation results show that our framework converges to accurate trust values faster than traditional methods, ensuring that reliable trust evaluations are made in real-time, even under high mobility conditions. The combination of these optimizations ensures that our framework is not only secure but also highly efficient, capable of supporting scalable and resilient VANET deployments. Furthermore, our decentralized approach ensures that trust decisions are made in real-time without the need for a centralized authority, making the system more adaptable to the high-mobility conditions of VANETs. This research offers a comprehensive solution for VANETs trust management, significantly improving communication efficiency, trust accuracy, and energy consumption while maintaining robust security and scalability. Our proposed blockchain-based trust management system provides a secure, energy-efficient, and scalable solution for VANETs, setting the stage for future developments in secure vehicular communication networks.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338618

    Lexical feature analysis of Chinese informed consent forms based on the information entropy methods: A paired study of minor and their guardian’ version

    by Qiansu Yang, Yining Wang, Wenbin Shi, Zhenzhen Li, Hong Liang, Jiang Cao, Nan Bai, Chien-Hung Yeh

    High-quality informed consent forms (ICFs) are crucial to facilitate effective communication between researchers and patients. However, the complex and specialized terminologies in ICFs often result in biased or late interpretations, thus hindering the ability to make decisions in line with their own will. Therefore, evaluating the readability of ICFs is an important task for Institutional Review Boards (IRBs) and regulatory agencies. This study proposes the use of information theory methods, including Shannon entropy and its extension—Rényi entropy (α values = 0, 0.5, and 1.5), as a set of comparisons, to quantify the lexical characteristics of Chinese ICFs, for either minors or their guardians. The Shannon entropy and Rényi entropy values of minor-version ICFs were significantly lower than those of guardian-version ICFs. The Shannon entropy and Rényi entropy with α = 1.5 of the ICFs for minors show no significant differences compared to those of the sixth-grade textbooks, while the Rényi entropy with both α = 0 and 0.5 shows no significant differences compared to the ninth-grade textbooks. This study utilized information entropies to assess lexical features of ICFs, as a pilot study to validate the feasibility of implementing Shannon and Rényi entropies to evaluate readability in Chinese ICFs.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338611

    High-protein diets reduce plasma pro-inflammatory cytokines following lipopolysaccharide challenge in Swiss Albino mice

    by Hellen W. Kinyi, Charles Kato Drago, Lucy Ochola, Gertrude N. Kiwanuka

    Macronutrients serve as principal sources of energy, structural components, and regulators of physiological processes. However, the optimal macronutrient combination for health remains unclear. While previous studies indicate that dietary macronutrient composition influences immune function, many have examined individual nutrients in isolation, failing to reflect the interactive effects of macronutrients. This study addresses this gap by examining how varying ratios of dietary carbohydrates, proteins, and lipids modulate serum cytokine responses to lipopolysaccharide challenge in Swiss albino mice. Male and female Swiss albino mice (n = 6 per group), aged 6–8 weeks, were randomly assigned to six purified isocaloric diets with differing macronutrient ratios for 15 weeks. Body weights were monitored to assess nutritional status. Serum levels of TNF-α, IL-6, IL-1β, and IL-10 were measured in unchallenged mice and after three hours of intraperitoneal LPS administration. Mice fed high-carbohydrate, low-protein diets had the highest weight (33.1 g ± 1.1), while those on high-lipid, low-protein diets had the lowest (28.3 g ± 0.6). Plasma levels of TNF-α and IL-10 varied significantly (p < 0.05) by diet in the unchallenged mice. IL-1β did not differ markedly (p = 0.085) across the dietary groups, and IL-6 levels were below the assay’s detection limit (<230.312 pg/mL). Following the lipopolysaccharide challenge, all cytokines increased, with significant differences among diets. Mice on high-protein diets exhibited notably lower TNF-α, IL-6, and IL-1β levels compared to those on high-carbohydrate or high-lipid diets. In contrast, IL-10 levels were higher in mice fed low-protein, high-carbohydrate, or high-lipid diets. In conclusion, high-protein diets appeared to dampen the responsiveness to lipopolysaccharide challenge, as indicated by smaller increases in pro-inflammatory cytokine levels, whereas high-carbohydrate and high-lipid diets elicited greater cytokine responses. We recommend that nutritional strategies aimed at modulating inflammation should ensure adequate dietary protein to help protect against both acute and chronic inflammation.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338588

    Study on the release pattern of Zn in soil of ionic rare earth mining areas under different leaching conditions

    by Zhongqun Guo, Qiangqiang Liu, Feiyue Luo, Shaojun Xie, Tianhua Zhou

    The acidic leachate injected during the mining process of ion-type rare earth ores can damage the environmental characteristics of the soil, thereby triggering the activation and release of associated heavy metals. Severe Zn contamination has been found in the environment of ion-type rare earth mining areas, but the activation and release of Zn in the soil during the leaching process have not been fully understood. This study investigated the activation and release patterns and mechanisms of Zn in soil under different leaching agents ((NH4)2SO4, MgSO4, Al2(SO4)3) and varying concentrations of Al2(SO4)3 (1%, 3%, 5%, 7%) using a simulated leaching experimental system. The results show that the activation and release patterns of Zn in the soil vary significantly under the influence of the three leaching agents. During the entire leaching cycle, the peak Zn concentration in the leachate was highest under MgSO4 leaching, while the residual Zn content in the soil under Al2(SO4)3 leaching approached the high-risk environmental threshold. The high-concentration systems (5%, 7%) of Al2(SO4)3 significantly enhanced the activation and release efficiency of Zn in the soil compared to the low-concentration systems (1%, 3%) of Al2(SO4)3. (NH4)2SO4 mainly promotes the activation and release of Zn through ion exchange between NH4+ and Zn2+ and the acidification effect; Al2(SO4)3, on the other hand, dominates the activation and release of Zn by providing a strongly acidic environment and dissolving and damaging the mineral lattice; while MgSO4 not only exchanges ions between Mg2+ and Zn2+, but also alters the soil colloidal structure, facilitating Zn activation and release. The promoting effects of the three leaching agents on the transformation of Zn in soil follow the order of Al2(SO4)3> (NH4)2SO4 > MgSO4, with the environmental risk assessment index (RAC) being highest after Al2(SO4)3 leaching, indicating the greatest potential environmental risk. Compared to the other three concentrations (1%, 5%, 7%) of Al₂(SO4)3, the 3% concentration of Al2(SO4)3 had the most significant promoting effect on the transformation of Zn in soil. This study provides a theoretical basis for optimizing the green mining process of ion-type rare earth ores and preventing heavy metal pollution, and offers scientific support for revealing pollution mechanisms and formulating remediation and risk assessment strategies.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338566

    Correction: Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review

    by Gaowei Fan, Kuo Zhang, Xin Yang, Jiansheng Ding, Zujian Wang, Jinming Li


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338537

    Investigating risk factors of hemorrhagic fever of renal syndrome (HFRS) in Qingdao, Shandong province, China

    by Ying Li, Jing Jia, Runze Lu, Liyan Dong, Lizhu Fang, Litao Sun, Zongyi Zhang, Qing Duan, Lijie Zhang, Kunzheng Lv, Huilai Ma

    Background

    Qingdao, a historically high-risk area for hemorrhagic fever with renal syndrome (HFRS) in China, is undergoing agricultural mechanization and urbanization. However, the specific risk factors for HFRS in this context remain unclear. This study sought to determine the risk factors for HFRS in Qingdao.

    Methods

    Community-based, 1:2 case-control study. Each case was matched with two healthy neighborhood controls based on biological sex, age, and the same neighborhood or village. Univariate and multivariate conditional logistic regression analyses were performed. Furthermore, stratified analyses were performed to explore risk factor heterogeneity between the peak season for Hantaan virus (HTNV) type HFRS (October-January) and other months.

    Results

    93 cases (73.2%, 93/127) reported from January 2022 to September 2023 and 186 controls completed this questionnaire. Farmers accounted for the highest proportion (68.8%, 64/93). In multivariate logistic regression analysis, there were three significant risk factors for HFRS: piles of firewood and/or grain in residential yards (odds ratio [OR]=3.75, 95% CI: 2.14–6.55), mite and/or flea bites (OR=1.83, 95% CI: 1.06–3.18) and contacting with rats and/or their excreta (OR=1.73, 95% CI: 1.09–2.74); three variables represented significant protective factors for HFRS: frequency of sun exposure for quilts and bedding (OR=0.41, 95% CI: 0.19–0.90), rodent control measures at home (OR=0.50, 95% CI: 0.30–0.81) and knowing the main sources of HFRS transmission (OR=0.58, 95% CI: 0.36–0.90). Stratified analysis revealed that the influence of these factors varied by season, with rodent contact and control measures being particularly salient during the HTNV peak season.

    Conclusion

    This study provides the first comprehensive evidence of risk and protective factors for HFRS in Qingdao, highlighting the role of rodent control, promoting comprehensive health education, environmental management, and personal protection. However, the results should be interpreted considering the study’s limitations, including a 73.2% response rate and the potential for recall bias.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338514

    A psycho-ecological signal recognition framework for user behavior prediction on digital media platforms

    by Lei Xiong, Ke Li, Wendy Siuyi Wong

    Background

    Digital media usage has become an integral part of daily life, but prolonged or emotionally driven engagement—especially during late-night hours—may lead to concerns about behavioral and mental health. Existing predictive systems fail to account for the nuanced interplay between users’ internal psychological states and their surrounding ecological contexts.

    Objective

    This study aims to develop a psychologically and ecologically informed behavior prediction model to identify high-risk patterns of digital media usage and support early-stage intervention strategies.

    Methods

    We propose a Dual-Channel Cross-Attention Network (DCCAN) architecture composed of three layers: signal identification (for psychological and ecological encoding), interaction modeling (via cross-modal attention), and behavior prediction. The model was trained and tested on a dataset of 9,782 users and 51,264 behavior sequences, annotated with labels for immersive usage, late-night activity, and susceptibility to health misinformation.

    Results

    The DCCAN model achieved superior performance across all three tasks, especially in immersive usage prediction (F1-score: 0.891, AUC: 0.913), outperforming LSTM, GRU, and XGBoost baselines. Ablation studies confirmed the critical role of both psychological and ecological signals, as well as the effectiveness of the cross-attention mechanism.

    Conclusions

    Incorporating psychological and ecological modalities through attention-based fusion yields interpretable and accurate predictions for digital risk behaviors. This framework shows promise for scalable, real-time behavioral health monitoring and adaptive content moderation on media platforms.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338507

    Mycobacterium tuberculosis complex lineages and drug resistance patterns among tuberculosis patients with or without diabetes mellitus in southern Ghana

    by Emelia Konadu Danso, Prince Asare, Amanda Yaa Tetteh, Phillip Tetteh, Augustine Asare Boadu, Ivy Naa Koshie Lamptey, Augustina Angelina Sylverken, Kwasi Obiri-Danso, Jane Sandra Afriyie-Mensah, Abraham Adjei, Dorothy Yeboah-Manu

    Drug-resistant (DR) tuberculosis (TB) and diabetes mellitus (DM) are intersecting epidemics that complicate management of both diseases and worsen patient outcomes. We conducted a prospective cohort study of 758 GeneXpert-confirmed pulmonary TB patients, of whom 75 had DM. Demographic, clinical, radiographic, and anthropometric data were collected at baseline. Sputum samples were cultured for mycobacterial isolation, and the obtained isolates were characterized for Mycobacterium tuberculosis complex (MTBC) lineage and drug-susceptibility testing using spoligotyping and microplate alamar blue assay. The TB-diabetes (TB-DM) comorbid cohort was older [TB-DM: 53/75 (70.7%) vs. 241/683 (35.3%) aged 41–60 years) (p < 0.001), included a higher proportion of females [TB-DM: 31/75 (41.3%) vs. TB-only: 150/683 (22.0%), p < 0.001], and had greater mean BMI (TB-DM: 23.36 ± 0.99 vs. TB-only: 19.97 ± 0.45 kg/m², p = 0.003). Analysis of 501 (TB-only: 448, TB-DM: 53) MTBC isolates revealed that TB-DM patients are more likely to get TB caused by L6 [TB-DM: 10/53 (18.9%) vs. TB-only: 37/448 (8.3%), p = 0.022] compared to the general TB population Lineage 4 [TB-DM: 36/53 (67.9%) vs. TB-only: 362/448 (80.8%), p = 0.046], Mycobacterial strains from TB-DM exhibited higher isoniazid mono-resistance [TB-DM: 15/50 (30.0%) vs. 42/288 (14.6%), p = 0.012] and harbored more multidrug-resistant TB [TB-DM: 5/50 (10.0%) vs. TB-only: 16/288 (5.6%), p = 0.215] although this did not reach statistical significance. These findings indicate that DM not only predisposes individuals to TB but may also shift the spectrum of infecting lineages and promotes the emergence of DR strains. Integrated TB-DM screening, lineage-aware diagnostics, and tailored treatment protocols are urgently needed in high-burden settings to address this dual threat.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338498

    Quantitative structure activity relationship (QSAR) modeling for adsorption of organic compounds by activated carbon based on Freundlich adsorption isotherm

    by Siyi Ding, Yefan Yang, Ting Tan, Qunshan Wei, Zhemin Shen, Qiong Liu, Xinshan Song, Yuhui Wang, Charles Nzila, Christopher W.K. Chow

    The Freundlich isotherm parameters K and 1/n are typically regarded as empirical constants. However, the underlying theoretical basis for the widespread applicability of the Freundlich isotherm in describing adsorption processes for diverse organic compounds remains unclear. In this study, we successfully elucidated the reason by developing two optimal quantitative structure-activity relationship (QSAR) models: one correlating K with quantum chemical parameters and another linking 1/n to these parameters. The modeling results demonstrated that both K and 1/n exhibit strong correlations with specific quantum chemical descriptors, indicating that the empirical Freundlich isotherm’s applicability is fundamentally linked to the molecular structural characteristics of organic compounds. Key quantum parameters influencing K were identified as ∑q(O + N), q(CH+)max, ELUMO, Fukui(-)max, and Wiberg(C-C)min, suggesting that charge distribution, carbon bond energy, and active site energy are the primary factors governing adsorption efficiency on activated carbon. The QSAR model for 1/n yielded similarly novel and consistent insights, showing that the value of 1/n also correlated with molecular structural characteristics. Both models were rigorously validated and confirmed to be stable, robust, and accurate through standard statistical evaluations. These QSAR models can now be employed to identify whether an organic compound would conform to the Freundlich Isotherm and predict the adsorption efficiency of this compound by activated carbon based on their quantum chemical parameters. As to the practical implications, this study provides a convenient reference method for assessing the applicability of activated carbon adsorption in treating emerging organic pollutants in drinking water plants and a theoretical foundation for developing intelligent management systems in water treatment facilities.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338483

    Health risk realization versus warning: Impact on lifestyle behaviours

    by Zoey Verdun

    Using individual-level panel data from Understanding Society I estimate the response to a health risk realization on a healthy lifestyle index. To overcome the endogeneity of a diagnosis, I match on initial health risks. I find individuals improve their overall lifestyle healthiness when faced with a large negative health event such as a heart attack or diabetes diagnosis, interpreted as a precise signal about their health status, whereas they do not respond to a noisier signal through solely receiving information about certain health risk factors, such as a diagnosis of high blood pressure or angina (chest pain). The drivers of the overall effect are a decrease in the number of cigarettes smoked and an increase in not drinking alcohol; there is no significant effect found for either diet or exercise. I find some heterogeneity by sex, but only when looking at individual lifestyle behaviours. Overall, the findings suggest that the realization of a health risk leads individuals to improve their lifestyle behaviours, while only a noisier signal about their health risks leads to no such change.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338311

    Prevention of Infections in Cardiac Surgery (PICS)-Prevena Study – A pilot/vanguard factorial cluster cross-over RCT

    by Thomas C. Scheier, Richard Whitlock, Mark Loeb, Philip James Devereaux, Andre Lamy, Michael McGillion, MacKenzie Quantz, Ingrid Copland, Shun-Fu Lee, Dominik Mertz

    Sternal surgical site infections after cardiac surgery can lead to significant morbidity, mortality, and cost. The effects of negative pressure wound management and adding vancomycin as perioperative antimicrobial prophylaxis are unknown. The PICS-PREVENA pilot/vanguard trial, a 2x2 factorial, open label, cluster-randomized crossover trial with 4 periods, was conducted at two major cardiac surgery hospitals in Ontario, Canada. Sites were randomized to one of eight sequences of the four study arms (Cefazolin or Cefazolin + Vancomycin (not analyzed) and standard wound dressing or a negative pressure 3M Prevena incision management system (Prevena). Only diabetic or obese patients were eligible for the latter comparison. This trial investigated feasability including adherence to protocol of each intervention (goal: > 90% each) and loss to follow-up (goal: < 10%). Among the 4107 included patients, 2230 were obese/diabetic (1208 standard wound dressing period, 1022 during Prevena period). Compliance to wound management and antimicrobial prophylaxis was 68.1% and 98.7%, respectively. Loss to follow-up was 3.6%. Deep/organ-space sternal surgical site infections occurred in 16 (1.6%) patients in the Prevena allocated periods and in 17 (1.4%) patients in the standard wound dressing allocated periods (OR= 1.11, 95% CI: 0.56–2.20). Other clinical outcomes did not suggest a difference and a post-hoc as-treated analysis showed similar results. This study showed challenges with introducing a novel technology as standard of care, with non-compliance mostly driven by one of the sites. No firm conclusions should be drawn regarding the effectiveness of Prevena, as this vanguard trial was not powered for clinical outcomes.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338300

    A disproportionality analysis of FDA adverse event reporting system (FAERS) events for filgotinib

    by Yinli Shi, Shuang Guan, Sicun Wang, Muzhi Li, Yanan Yu, Jun Liu, Weibin Yang, Zhong Wang

    Background

    Although filgotinib, a selective Janus kinase 1 inhibitor, has been increasingly applied in the treatment of inflammatory diseases, its comprehensive safety profile remains insufficiently characterized. Using data from the FAERS database covering Q1 2014 to Q2 2024, this study attempts to analyze adverse event signals linked to filgotinib and provide guidance for the safe and sensible clinical usage of filgotinib.

    Methods

    From Q1 2014 to Q2 2024, information on adverse drug events (ADEs) associated with filgotinib was gathered. The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) were among the signal detection methods that were employed for analysis following data normalization.

    Results

    Filgotinib was shown to be the main suspected medication in ADE reports, exposing 103 preferred terms (PTs) in 17 system organ classes (SOCs). Infections, gastrointestinal disorders, and musculoskeletal and connective tissue disorders were the most commonly reported adverse effects. Additionally, atrial fibrillation, alopecia, elevated serum creatinine, blood creatinine increased, pulmonary embolism, epididymitis, respiratory failure, and osteopenia were identified as potential disproportionate reporting signals for filgotinib, although these were not listed in the official drug label. Notable significant signals included large intestine erosion (ROR 2186.05, 95%CI(ROR): 1015.94–4703.86, PRR 2176.18, 95%CI(PRR): 1014.64–4667.42), mesenteric arterial occlusion (ROR 1832.17, 95%CI(ROR): 897.68–3739.48, PRR 1822.71, 95%CI(PRR): 896.17–3707.20), repetitive strain injury (ROR 1149.27, 95%CI(ROR): 363.16–3637.01, PRR 1147.05, 95%CI(PRR): 363.24–3622.15), oligoarthritis (ROR 755.02, 95%CI(ROR): 310.74–1834.54, PRR 752.59, 95%CI(PRR): 310.60–1823.51), and periostitis (ROR 676.03, 95%CI(ROR): 319.36–1431.06, PRR 672.98, 95%CI(PRR): 318.97–1419.87). The subgroup analysis identified obvious sex and age-specific trends in filgotinib-related adverse reactions, emphasizing a higher risk of renal disorders in females, a preponderance of gastrointestinal events in males, and age-dependent trends involving mesenteric occlusion, increased serum creatinine, and immunoglobulin reduction.

    Conclusion

    While filgotinib demonstrates therapeutic efficacy, it is associated with a range of potential adverse events, underscoring the need for vigilant clinical monitoring. Particular attention should be given to gastrointestinal, cardiovascular, respiratory, and metabolic complications.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338188

    The willingness and perceptions of Surinamese individuals in the Netherlands on living tissue donation: A qualitative and exploratory study

    by Charifa Zemouri, Assia Nait Kassi, Muriel Sinselmeijer, Bert Elbertse, Yvonne Mulder, Sara Jobse, Ilyaz Nasrullah, Jennifer Jubitane, Shelaika Hoogdorp, Eva-Maria Merz

    Background

    The Surinamese population in the Netherlands is an ethnically diverse group with a specific need for transfusion or transplantation due to a higher prevalence of diseases like beta-thalassaemia and sickle cell disease. This study explored the willingness of Surinamese individuals in the Netherlands to donate blood, stem cell, and live organ donation, and preferred information dissemination methods.

    Methods

    A sequential, qualitative, exploratory study was conducted using an online questionnaire and a focus group to examine the willingness to donate living tissue. Participants were Surinamese individuals aged 18–55 residing in the Netherlands. The questionnaires were inductively thematically analysed. The results led to in-depth questioning and discussion among the focus group, which consisted of four men and four women. The session was recorded and transcribed verbatim for thematic analysis.

    Results

    We identified ten themes across tissue types: 1) awareness of needs; 2) information and knowledge; 3) donation process; 4) cues to action; 5) attitude; 6) religion; 7) health challenges; 8) fear; 9) social cohesion and solidarity; 10) relationship with recipient. Willingness to donate blood was high, but they faced barriers, including registration challenges and limited access. Stem cell donation was seen as invasive. Living organ donation was considered only for emotionally close recipients. Participants were unaware of shortages and the importance of ethnic matching. They called for inclusive campaigns reflecting broader ethnic diversity, not just Suriname. Future strategies should simplify access to information, registration, and donation processes.

    Conclusion

    Most participants were unfamiliar with living donations, and perceived barriers were key reasons for not donating. Emotional bonds and awareness of ethnic matching and shortages motivated willingness. Participants stressed the need for tailored, ethnic-specific campaigns to address barriers and misconceptions, emphasise ethnic matching, and highlight reliance on their communities for successful living donation.


    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338125

    The effect of life stress on the public participation of rural youth in China

    by Jinhua Liu, Yichi Zhang

    Youth are pivotal participants in public engagement. They use public participation to promote societal change and improve living conditions, thereby coping with life stress. Against the backdrop of rural-urban disparities in geography and socio-economic development, rural youth face limited access to information and narrower channels for public participation. Moreover, scholarly exploration of life stress among rural youth remains scant. To investigate how life stress among rural youth influences their public participation behavior, this study used data from the “Chinese Social Survey” for empirical analysis, with a total sample size of 1624 individuals and an average age of 27 years. The findings indicated that lower family stress encourages rural youth to engage in mutual cooperation and collective rights protection, while higher social stress promotes the more active expression of attitudes and participation in decision-making. To enhance the public participation of rural youth, and elevate their engagement levels, recommendations include focusing on managing life stress and promoting psychological well-being, strengthening social support networks for rural youth, initiating family education programs, devising differentiated economic support policies, and intensifying advocacy for rural youth rights and public affairs.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338097

    Integrating human–AI collaboration into translation education: A comprehensive protocol for assessment, diagnosis, and strategy development

    by Xiaobin Ren, Ruoxuan Wang

    In the era of artificial intelligence (AI), translation education faces pressing challenges to integrate human–machine collaboration into talent cultivation. This study protocol outlines a two-year mixed-methods project that focuses on developing, validating, and applying systematic tools for assessing human–machine collaborative competence among translation students and teaching competence among translation instructors. In the first stage, measurement instruments will be constructed and validated through thematic analysis, exploratory and confirmatory factor analysis, based on interviews, pilot testing, and large-scale surveys. The second stage will employ grounded theory, structural equation modeling, and regression analysis to identify the factors influencing students’ and teachers’ competence development. The third stage will investigate industry needs through semi-structured interviews with translation service professionals and descriptive statistical analysis across multiple domains. The fourth stage will assess classroom effectiveness via multimodal analysis of teaching and learning processes across five types of universities. Finally, a comprehensive training strategy will be designed, refined through action research pilot implementations, and validated by Delphi consultation with translation educators, industry specialists, and policymakers. By integrating empirical rigor with iterative validation, this study advances theoretical modeling of human–AI collaboration, establishes robust assessment tools for students and teachers, and delivers actionable training strategies that align translation education with evolving professional and industry needs.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0338089