PLoS ONE最新文献

Objective: The triglyceride-glucose index and estimated glucose disposal rate serve as notable surrogate markers of insulin resistance, demonstrating established links to cardio-cerebrovascular disease. However, their combined prognostic value in predicting cardio-cerebrovascular disease outcomes remains unexplored. The current investigation examined the interaction between the TyG (triglyceride-glucose index) index and eGDR (estimated glucose disposal rate) concerning the danger of cardiovascular disease within a clinical population.

Methods: This investigation employed data sourced from the China Health and Retirement Longitudinal Study (CHARLS). The median TyG index and eGDR scores were used to stratify the participants into 4 categories: low TyG/high eGDR, high TyG/high eGDR, low TyG/low eGDR, and high TyG/low eGDR. Clinical characteristics across groups were systematically compared. Cox proportional hazards regression models evaluated the distinct and interconnected associations of the TyG index and eGDR with the risk of cardio-cerebrovascular disease, with multiplicative and additive interaction effects subsequently assessed through formal interaction analysis.

Results: The final study cohort comprised 7,330 participants, with 1,336 individuals (18.2%) developing cardio-cerebrovascular disease during the 9-year follow-up. Stratification using median thresholds (TyG: 8.59; eGDR: 10.55 mg/kg/min) yielded four groups: low TyG/high eGDR (n = 2,991), high TyG/high eGDR (n = 1,375), low TyG/low eGDR (n = 1,372), and high TyG/low eGDR (n = 2,292). Multivariable-adjusted Cox regression analyses revealed markedly increased risks of cardio-cerebrovascular disease among the various exposure groups when contrasted with the low TyG/high eGDR reference: high TyG/high eGDR (HR: 1.31, 95%CI: 1.10-1.57, p< 0.05), low TyG/low eGDR (HR: 1.54, 95%CI: 1.29-1.84, p< 0.05), and high TyG/low eGDR (HR: 1.55, 95%CI: 1.31-1.82, p< 0.05). Interaction analysis revealed significant multiplicative effects between TyG and eGDR but no evidence of additive interaction.

Conclusion: The TyG index and eGDR demonstrate independent associations with cardio-cerebrovascular disease risk, while their combined assessment reveals synergistic predictive capacity. Combined assessment of the two allows for further accurate stratification of the population based on insulin resistance and improved prediction of cardio-cerebrovascular disease.

Introduction: Patients with significant liver fibrosis (SF) are likely to progress to advanced chronic liver disease (ACLD). Therefore, liver-directed therapy is indicated. The European Association for the Study of the Liver-2024 (EASL) recommends annual screening of patients with diabetes for SF/ACLD using the FIB-4 score, followed by vibration-controlled transient elastography (VCTE) in patients with FIB-4 ≥ 1.3 in ≤65-year-olds and ≥2.0 in > 65-year-olds. Because VCTE is not freely available in resource-limited settings, we revised the EASL algorithm to prioritise referrals for VCTE in such settings and validated it in an external cohort.

Methods: We conducted a cross-sectional study of adults with type 2 diabetes (T2DM) and ultrasonographic evidence of steatotic liver disease (SDL) attending three outpatient medical clinics in the Gampaha District, Sri Lanka. FIB-4 scores were calculated, and those with scores ≥1.3 underwent VCTE. SF was defined as liver stiffness measure (LSM) ≥ 8.0 kPa. Factors significantly associated with SF/ACLD were identified using multiple logistic regression (LR). We then developed a new criterion for VCTE referral and compared the number of referrals for VCTE when using the new criterion-based algorithm with the EASL algorithm. We validated the new criterion-based algorithm in an external cohort of 372 patients with MASLD.

Results: We studied 363 patients, and 128 had an FIB-4 score of≥1.3. Of them,121 underwent VCTE, and 76 had an LSM ≥ 8.0 kPa. On multivariable LR, VCTE-diagnosed SF/ACLD was independently associated with diabetes of ≥ 5 years duration (OR 3.8, p = 0.035), micro/macrovascular complications (OR 19.4, p = 0.016), and BMI of ≥ 25 kg/m2(OR 6.2, p = 0.003). We revised the VCTE referral criterion as "patients having EASL FIB-4 criterion plus one or more of the three other factors: diabetes of ≥ 5 years duration, presence of micro/macrovascular complications or BMI≥25 kg/m2,". The number of VCTE referrals indicated using the EASL algorithm was 96, compared to 83 with the new criterion, resulting in a 13.5% reduction. In the external validation cohort, the new algorithm reduced the number requiring VCTE referral by 15.5%.

Conclusions: Adopting the new criterion for VCTE referral in patients with MASLD appears more cost-effective for detecting SF/ACLD in low-resource settings in South Asia.

Acute kidney injury (AKI) remains a major clinical challenge due to its high morbidity and mortality, with ischemia-reperfusion injury (IRI) as one of its primary causes. Severe IRI-associated AKI (IRI-AKI) can progress to irreversible renal failure, yet no effective therapies are currently available. Ferroptosis, an iron-dependent regulated cell death, has recently been implicated in the pathogenesis of IRI-AKI. Moreover, IL-22 may alleviate AKI by modulating the ferroptosis process through regulation of the P62-Keap1-Nrf2 signaling axis. In this study, we examined the protective role of the immune cytokine interleukin-22 (IL-22) in IRI-AKI and its mechanistic association with ferroptosis. Using a murine IRI model and an HK-2 cell hypoxia/reoxygenation system, we systematically assessed the impact of IL-22 treatment. IL-22 administration significantly enhanced renal function, reduced histological injury, and limited both reactive oxygen species accumulation and ferroptotic cell death. Further mechanistic studies demonstrated that IL-22 suppresses ferroptosis in vitro through an Nrf2-dependent mechanism and is associated with activation of the P62-Keap1-Nrf2 signaling pathway. These findings offer experimental evidence supporting IL-22 as a potential therapy for IRI-AKI and highlight ferroptosis modulation as a promising therapeutic strategy.

Sepsis is a life-threatening state of disseminated infection, and treatment requires knowledge of the organism responsible. The gold standard for sepsis diagnosis is blood culture, which requires days of growth. Next-generation sequencing has been proposed as an alternative; however, existing methods may lack sensitivity. In this work, we explore the idea of genomic quasi-G-primes, which are short DNA sequences specific to a single species within a group of relevant species. We first validated the genomic quasi-G-prime classification in controlled Staphylococcus aureus sequencing experiments, and then applied the same approach to blood-derived sequencing data from septic and healthy patients, where genomic quasi-G-prime profiles distinguished disease states. Our method is highly space-efficient, permitting fast classification on modest hardware and enabling it to outperform existing taxonomic classification approaches in this task.

Virtual Reality Development Centres (VRDCs) represent a recent extension of Assessment Center (AC) methodology, yet empirical evidence on their validity and their relationship to established evaluation systems remains limited. This study addresses this gap by examining how VRDC assessments-grounded in immersive, real-time behavioral observation-converge with traditional 270-degree evaluations and self-assessments across five managerial competencies. Using a sample of 64 mid-level managers who completed 16 VRDC sessions and parallel 270-degree evaluations, we tested three hypotheses concerning convergent validity and unique diagnostic value. VRDC demonstrated strong inter-rater reliability (rwg = .82-.95; ICC(2) =.76-.92) and showed significant alignment with 270-degree ratings for managing people and tasks, goal orientation, and change management, but not for decision-making or cooperation. Self-assessments correlated with VRDC only for cooperation, and negatively for managing people and tasks, revealing consistent self-perception biases. Across all competencies, VRDC provided diagnostic insights not captured by self-report, supporting its added theoretical value. The findings contribute to theory by clarifying the distinct construct domains captured by immersive behavioral simulations versus retrospective, perception-based evaluations. We argue that VRDC should be conceptualized not merely as a technological enhancement, but as a methodological bridge that integrates AC logic with multi-source frameworks. Practically, VRDC offers organizations a reliable and context-sensitive tool for assessing crisis-relevant competencies, complementing-but not replacing-traditional evaluation methods. The study advances the theoretical understanding of VR-based assessment and informs the development of multimethod competency assessment systems.

The regenerative capacity of mammalian RGC neurites after damage, such as glaucoma, is limited. Numerous studies have utilized herbal extracts to promote neural regeneration and exert neuroprotective effects in the hope of mitigating glaucoma. In the present study, we investigated the effect of extracts from the cicada fungus (Cordyceps cicadae) and the Lion's mane mushroom (Hericium erinaceus) on neurite outgrowth of retinal explants and isolated RGCs. We also examined whether these extracts affect the number of apoptotic cells and neurite outgrowth activity of RGCs. The results showed that an aqueous extract of Cordyceps cicadae, an ethanol extract of Hericium erinaceus, and the purified compound Erinacine Sare able to promote neurite outgrowth in retinal explants. Given its role as a key bioactive compound, Erinacine S was further investigated on isolated RGCs, where it also significantly enhanced neurite outgrowth, demonstrating a direct effect on RGC regeneration. In addition, these extracts have no significant drawbacks in terms of cell apoptosis and RGC neurite outgrowth activity at specific concentrations. The present study thus demonstrates that while excessively high concentrations of these extracts may inhibit neurite growth, at moderate concentrations some extracts from Cordyceps cicadae and Hericium erinaceus have the potential of promoting neurite regeneration in the mammalian retina. Further research targeting the molecular mechanisms behind these effects may shed light on their potential application as a medicine or nutraceutical for facilitating neural regeneration.

Introduction: The Primary Care Assessment Tool (PCAT) is designed to assess a patient's experience with primary care across various core and ancillary domains, including First contact - Utilization, First contact - Access, Ongoing Care, Coordination, Comprehensiveness (services provided), Family-centeredness, Community Orientation, and Cultural Competence. This study examined the psychometric properties of the Adult Primary Care Assessment Tool Short Form (PCAT-S) in the Australian general practice setting.

Method: Data included 715 participants from the EQuIP-GP study, a cluster randomized controlled trial (RCT) conducted with adults aged 18-65 years with a chronic illness or aged over 65 years, from 34 general practices across Australia. For each subscale we assessed internal consistency using Cronbach's alpha. Factor structure of the PCAT-S instrument was assessed through confirmatory and exploratory factor analysis, using three samples with different methods for handling 'don't know/can't remember' responses.

Results: The findings were mixed. Specifically, the subscales related to First Contact - Utilization, Ongoing Care and Comprehensiveness, demonstrated satisfactory internal consistency. However, the remaining subscales showed weak internal consistency. Confirmatory factor analysis indicated potential model misspecification, while exploratory factor analysis generally supported the hypothesized factor structure, albeit with some observed deviations.

Conclusions: The findings indicate the PCAT-S shows promise as an instrument to evaluate primary care experiences in Australia. However, the observed variability in internal consistency, along with issues identified in confirmatory and exploratory factor analyses, highlight the need for further validation and refinement in this population. Further research is required to address the identified limitations and enhance the tool's applicability within the Australian general practice context.

Having to control multiple tasks in parallel poses challenges for humans and artificial agents alike. In artificial intelligence, specific forms of reinforcement learning (RL), most notably hierarchical and model-based RL, have shown promising results in scenarios where tasks or skills need to be switched adaptively. However, RL agents still encounter difficulties when faced with serial multitasking that involves switching control between continuously running subtasks, such as changing the radio station while driving in traffic. Inspired by human cognitive processes, we hypothesize that maintaining a sense of control is a key mechanism facilitating such task-switching decisions. We propose a mathematical formulation of a situational sense of control that consists of two components: an evaluative indicator of the predictability of action outcomes and a predictive indicator of a need for control in individual subtasks. We integrate this model of a sense of control into a hierarchical RL agent and evaluate its performance in a Collect Asteroids game environment, in which one must alternate between navigating two spaceships to collect as many asteroids as possible. Comparing RL agents with and without a sense of control, as well as with human participants, shows that equipping RL agents with a sense of control results in significant performance improvements. Our findings indicate that agents equipped with a sense of control prioritize more complex tasks, exhibit increased switching behavior, and make switches at strategically optimal times, leading to superior overall performance. The incorporation of cognitive mechanisms, inspired by human behavior, into RL agents thus appears to yield considerable enhancements in performance when acting in complex and dynamic environments.

Background: The objective of this study was to assess the household costs, catastrophic out-of-pocket (OOP) health expenditure, impoverishment and coping mechanisms used to pay for surgical care in a predominantly rural area of Ethiopia.

Methods: We conducted a community-based, cross-sectional household survey of 182 people who had undergone a surgical procedure. Participants were interviewed in their homes at six weeks post-operation. Using a contextually adapted version of the Study of global AGEing and adult health (SAGE) questionnaire, we estimated direct and indirect costs of surgical care from a household perspective. Catastrophic out-of-pocket (OOP) health expenditure was estimated using thresholds of 10% and 25% of annual household consumption expenditure. Impacts of surgical care payments on poverty levels was estimated by comparing pre- and post-operative OOP payments. Analysis of variance, t-test and a logit model were used to assess factors associated with catastrophic OOP health expenditure.

Results: Most surgical patients were women (87.9%), with 65.0% receiving obstetric surgical care. Direct costs dominated expenditure: direct average medical costs Birr 1649.5 (44.6%), direct average non-medical costs Birr 1226.5 (33.2%), indirect average costs Birr 821.9 (22.2%). Catastrophic OOP surgical care expenditure was experienced by 69.2% households at the 10% threshold and 45.6% at the 25% threshold. The increase in average normalized poverty gap due to OOP surgical care expenditure was higher in non-obstetric (14.1%) compared to obstetric (5.8%) procedures, and for non-emergency (13.3%) compared to emergency care (6.3%). To pay for surgical care, 38.0% of households had sold assets and 5.0% had borrowed money.

Conclusions: Due to surgical care, households faced severe financial burdens leading to impoverishment. To mitigate the resulting financial constraints, households implemented hardship coping strategies. Provision of free obstetric surgical care reduced, but did not eliminate, these burdens. There is a pressing need to tailor financial risk protection mechanisms to achieve universal coverage for surgical care.