PLoS ONE最新文献

Introduction: HIV/AIDS remains a major public health issue, with about 1.4 million people infected in Uganda by 2020. In rural western Uganda, 57.6% of people living with HIV (PLWH) use herbal medicine (HM) alongside antiretroviral therapy (ART). Combining HM with a tenofovir disoproxil fumarate (TDF)-based ART regimen may increase risks of renal dysfunction, death, and treatment costs, highlighting the need to study their combined effects.

Objective: To determine the prevalence of herbal medicine use and its association with renal dysfunction among patients on tenofovir antiretroviral treatment-based regimen at ISS clinic Mulago.

Methods: A cross-sectional study at MJAP ISS-clinic involved 414 HIV/AIDS patients on TDF-based ART from March-May 2023. Data on herbal medicine use and ART regimen were collected via interviews; blood samples were taken for renal function. Additional clinical and demographic data were extracted from records. All data were entered into Epidata and analyzed using STATA version 17.

Results: We enrolled 414 participants with median age (interquartile range) of 36 (30,44) years, majority were female 290 (70.1) and were on firstline regimen 392 (94.7). The prevalence of herbal medicine use was 70.8% (95% CI 66.2-74.9). The commonly used herbal medicines reported were concoction/crude, medicated clay and powdered products. The overall renal dysfunction prevalence was 22.5% (95 CI 18.7-26.8) The median serum creatinine levels among herbal medicine users was 96 µmol/litre and 88.8 µmol/litre among non-users. There was a significant difference in the median serum creatinine in the two groups (P = 0.028). There was no significant difference in the urea levels in the two groups (2.99 mmol/litre in herbal medicine users versus 2.84 mmol/litre in non-users, P = 0.689). Herbal medicine use was significantly associated with renal dysfunction (aPR-2.31, 95% CI 1.35-3.97). Other factors that were associated with renal dysfunction were age (aPR-1.54, 95% CI 1.08-2.22) sex (aPR-0.52, 95% CI 0.33-0.83), hypertension (aPR-3.43, 95% CI 2.47-4.76) and diabetes (aPR-1.79, 95% CI 1.39-2.31).

Conclusion: Health care workers should screen for herbal medicine use among ART patients and regularly monitor their renal function to detect dysfunction. The Ministry of Health and health care workers should also emphasize educating patients about the potential risks of combining herbal medicine with ART.

At the micro-scale channel dimensions and relatively low Reynolds numbers, fluids can only mix through diffusion in a laminar flow state. This dependence on molecular diffusion significantly hinders the mixing performance of microfluidic chips. To address this issue and promote the application of microfluidic technology in the detection of heavy metal ions, we propose a high-performance microfluidic chip with variable cross-sectional channels based on passive mixing. By setting bias centrifugal bends and linear flow channels with periodic diameter changes, the mixing efficiency of the microfluidic chip has been significantly improved. To verify the theoretical mixing effect, we set up eight groups of different Reynolds number conditions for the microfluidic chip and simulated the fluid flow in laminar state. Through analyzing the simulation cloud diagrams and the mass fraction mixing index, it was found that when the Reynolds number was 0.5, the mixing efficiency of the microfluidic chip reached the optimal state, with a mass fraction mixing index of 0.9998, and the pressure drop was only 0.1502 Pa, which was higher than the mixing efficiency of similar chips under the same conditions. Using 3D printing technology to fabricate the microfluidic chip and conducting characterization analysis. To verify the actual mixing effect, a colorimetric mixing experiment was set up, and a visual mixing effect analysis of the chip was conducted. Through ICP-MS for copper ion detection experiments, three control experiments were set up to conduct a data-driven mixed effect comparison analysis of the chip. After verification, the overall and local mixing effects of the microfluidic chip were highly consistent with the simulation results under the same conditions, and the detection value of the mixed solution was 101.99% of the completely mixed solution, showing good consistency. Therefore, this chip has excellent mixing performance and is conducive to promoting the application of passive microfluidic chips in fields such as heavy metal detection.

Introduction: The joints of the upper extremity are responsible for ensuring the safe movement of the body when steering and shifting gears. The impact of wrist immobilization and the subsequent movement limitations on driving ability remains inconclusively elucidated. The aim of the pilot study was to determine the range of motion required to safely operate a motor vehicle when the right wrist is immobilized. In addition, the compensators mechanisms that occur in this situation and enable safe driving to continue were to be Identified.

Materials and methods: A total of 20 healthy subjects were studied as part of a driving simulation in a stationary driving simulator. The right wrist was immobilized, and all subjects were required to complete a standardized driving program consisting of representative driving maneuvers (A) shifting gear, B) left turns, C) right turns). To evaluate driving performance, speed, lane keeping, and shifting time were assessed using the driving simulator. In addition, the range of motion of the upper extremity, spine, and hip were collected using the motion capture system.

Results: The average age of the 20 healthy participants was 28.2 years, and 40% were female. The elimination of the right wrist does not result in a significant reduction in driving performance. During the act of shifting gears, a significant decrease in extension was observed in the right elbow (p = 0.002; 95% CI [-6.13, -1.57]), while a significant increase in abduction in the right shoulder joint (p = 0.008; 95% CI [-7.46, -1.28]) and flexion in the spine was observed (p = 0.011; 95% CI [-1.48, -0.22]). During a right-hand turn in the road, compensation occurs via the right elbow with a significant reduction in both maximum flexion (p = 0.008; 95% CI [2.98, 17.22]) and maximum supination (p = 0.005; 95% CI [-20.96, -4.34]). Conversely, when turning left, there is compensation via the left upper extremity: There is a significant increase in ulnar abduction of the left wrist (p = 0.03; 95% CI [-5.87, -0.33]) and minimal flexion of the left elbow (p = 0.012; 95% CI [1.22, 8.88]).

Conclusion: Our data suggest that driving with an immobilized right wrist can be well compensated in healthy adults, although biomechanical changes in the upper extremity and spine were observed.

Objective: Developing communication skills early during medical training requires structured opportunities for practice, observation, and reflection. This study integrated video-recorded peer role-play with a standardized checklist to foster communication skill competencies among first-year medical students.

Methods: A communication skills module was designed for 250 first-year MBBS students as part of the Attitude EThics COMmunication (AETCOM) course. The intervention integrated video-based submission of peer role-play of doctor‒patient interviews guided by a standardized, culturally contextualized checklist (Observation-Based Communication Skills Checklist; OCSC). The entire module was managed through the institutional learning management system (LMS). Student perceptions were gathered via a validated questionnaire and two focus group discussions (FGDs).

Results: Of 241 valid submissions, 70% met expectations, and 28% exceeded them. Student feedback was overwhelmingly positive, with 87% agreeing that peer role-play was an effective learning method. A majority (91%) reported that the OCSC-guided video assignment provided a structured and reflective learning experience. Thematic analysis of FGDs revealed that checklist-guided role-play was helpful for skill acquisition, video assignment consolidated learning, and faculty feedback was crucial for improvement.

Conclusion: The integration of video-recorded peer role-play, a standardized checklist, and an LMS provides a scalable and effective framework for teaching, assessing, and reinforcing foundational communication skills in early-phase medical learners.

Background: At present, the early warning of difficult airway remains fraught with challenges. Previous ultrasonic quantitative parameters have demonstrated favorable application potential in difficult airway assessment, and deep learning techniques have also exhibited satisfactory performance in the interpretation of this condition. Based on this, we aim to construct a "two-model, three-step" hierarchical strategy, develop an ultrasound image-based artificial intelligence (AI) framework for difficult airway prediction, and conduct its internal validation.

Methods: In this study, we included 903 patients who underwent elective general anesthesia surgery at the Affiliated Hospital of Qingdao University between May 2024 and April 2025. 752 cases were used for model training and validation, and 151 cases served as an internal test set. Four planes of neck ultrasound images were scanned for each patient and used to develop two artificial intelligence models (based on convolutional neural networks): CL-AI for initial screening and VIDIAC-AI for secondary risk stratification. Model performance was evaluated using five-fold cross-validation and internal testing. External validation was not performed.

Results: Among 903 patients, difficult laryngoscopy occurred in 189 cases (20.9%) under direct laryngoscopy and in 50 cases (5.5%) under video laryngoscopy. In the independent test set, the CL-AI model achieved an AUC of 0.86 (95% CI: 0.79-0.91), with an accuracy of 0.84, sensitivity of 0.84, specificity of 0.84, precision of 0.59, and an F1 score of 0.69. The VIDIAC-AI model achieved an AUC of 0.82 (95% CI: 0.75-0.88), with an accuracy of 0.81, sensitivity of 0.75, specificity of 0.81, precision of 0.18, and an F1 score of 0.29.

Conclusions: This study proposes an ultrasound-based AI framework for risk stratification of difficult laryngoscopic exposure. The Two-Model, Three-Step decision framework is intended as a clinician decision-support tool, not an independent diagnostic method, and requires further validation in large multicenter cohorts.

The global biscuit market is shifting towards healthier, gluten-free options, demanding novel and sustainable ingredients. This research introduces Nipa palm kernel flour (NFK) an underutilized, gluten-free resource from the mangrove Nypa fruticans Wurmb as a promising functional ingredient for biscuit production. Mature fruits were collected from the Sundarbans, Bangladesh, to develop nutritious snacks and valorize this sustainable resource from an underutilized plant. Kernels were extracted, blanched, dried, and milled into flour. Biscuits were formulated by substituting refined wheat flour with 0% (control), 10%, 20%, and 30% NFK. The physical, nutritional, sensory, and shelf-life properties of the biscuits were comprehensively analyzed using standard methods. NFK incorporation significantly improved the biscuit's nutritional profile. The 30% NFK biscuit exhibited a 38% reduction in fat, a seven-fold increase in crude fibre (from 0.19% to 1.35%), and a substantial boost in essential minerals, with iron content more than doubling to 53.3 mg/kg. Incorporating NFK significantly altered the biscuits' color profile, reducing lightness (L: 65.30 to 55.40) and yellowness (b: 25.80 to ~22.50-23.10) while increasing redness (a*: 4.50 to ~5.85-6.10), resulting in a desirable, darker red-brown hue. Crucially, all NFK-enriched biscuits received high sensory acceptability scores (≥7.85 on a 9-point scale), with no significant difference in overall liking compared to the control. Microbiological analysis confirmed product safety and a shelf life of over 12 months. The incorporation of Nypa fruticans kernel (NFK) flour at 15% substitution significantly enhanced the biscuits' functional profile, increasing total phenolic content by 212% (to 265.8 mg GAE/100g) and flavonoid content by 174% (to 89.1 mg QE/100g). This directly boosted antioxidant capacity, with DPPH IC₅₀ decreasing 3.3-fold (to 3.8 mg/mL) and FRAP value increasing 4.6-fold (to 8.2 mmol Fe2 ⁺ /100g), transforming the biscuit into a potent bioactive food carrier. NFK is a promising gluten-free biscuit ingredient. Future research should confirm large-scale production, in-vivo bioavailability, and precise compound characterization, supporting sustainable mangrove use and healthy food choices.

Background: The understanding of recovery after critical COVID-19 beyond the first year is limited.

Objectives: To describe changes in functional, physical, and mental health outcomes between 1 and 3 years among survivors of critical COVID-19 and to identify factors associated with incomplete recovery at 3 years.

Methods: A prospective multicentre cohort study of survivors of critical COVID-19 with follow-up at 1 and 3 years. The primary outcome was functional outcome, assessed using the Glasgow Outcome Scale-Extended (GOSE), which ranges from 1 to 8, with scores of 6 or less indicating incomplete recovery. Secondary outcomes included return-to-work, physical and mental Health-Related Quality of Life (HRQoL), life satisfaction, fatigue, psychological symptoms (anxiety, depression, post-traumatic stress disorder), and respiratory symptoms. Multivariable logistic regression was used to identify factors associated with incomplete recovery (GOSE ≤ 6) at 3 years.

Results: Among 191 of 210 eligible participants, functional outcome declined from 1 to 3 years, and participants with incomplete recovery increased from 32% to 45%. Worse outcomes were observed in mental HRQoL, fatigue, depression, and post-traumatic stress, while return-to-work rates, physical HRQoL, life satisfaction, anxiety, and respiratory symptoms remained stable. Younger age [OR 0.70 (95% CI 0.54-0.91), p = 0.008] and higher Clinical Frailty Scale score [OR 1.54 (95% CI 1.04-2.28), p = 0.029] were independently associated with incomplete recovery at 3 years.

Conclusions: Survivors of critical COVID-19 experienced a decline in functional outcome and worsening mental health between 1 and 3 years after ICU admission. Younger and frail survivors may require increased attention and support.

Trial registration: ClinicalTrials.gov Identifier: NCT04974775, registered April 28, 2020.

Mucormycosis is a life-threatening fungal infection with limited treatment options and high mortality rates among immunocompromised individuals. To identify new therapeutic strategies, we screened a library of 618 antiviral compounds against Rhizopus delemar both alone and in combination with amphotericin B (AmB) to search for agents with intrinsic antifungal activity or the ability to enhance AmB's efficacy. Four candidates, IMB-301, U18666A, BLT-1, and obefazimod, showed potent in vitro effects, with three sustaining growth suppression comparable to AmB for up to 48 h in time-kill assays. The hepatitis C antivirals daclatasvir (DAC) and velpatasvir (VEL) demonstrated strong synergy with AmB across Mucorales isolates, lowering AmB MICs by 4- to 32-fold (ΣFICI < 0.5) and achieving fungistatic suppression of R. delemar at subinhibitory AmB concentrations (0.25 µg/mL). Importantly, neither the standalone antivirals nor their combinations with AmB reduced Vero cell viability at concentrations exceeding 4-16 × their MICs, while selectivity indices ranging from 8 to >32 indicated favorable safety margins. These findings highlight antiviral repurposing as a promising strategy to expand treatment options for mucormycosis and support further translational development.

Background: Inequality in palliative care provision is an ongoing problem for underserved groups, such as those with heart failure (HF) placing a burden on patients, their caregivers and health services due to frequent, often avoidable hospitalisations. Our realist synthesis of integrated palliative care (PC) and HF literature found that integrated HF and PC services work best when service providers are motivated and have the opportunity and capacity to support behaviour change. However, we identified significant knowledge gaps with most studies completed in United States of America (USA) and based primarily on the views of nurses and physicians. We developed strategies to help services provide integrated PC and HF services but identified the need for United Kingdom (UK) primary data to better understand the context-specific implementation of palliative care and HF care.

Methods: This project will use co-design and realist evaluation to generate data from five PC and HF integrated services in the UK, purposively sampled to provide variation in geography and service design (Research Registry 10624). The research comprises three work packages (WPs). WP1 will deliver a realist evaluation of each site including documentary analysis, observations and semi-structured interviews with service providers and users. WP2 uses co-design methods to develop a guide to help others set up and improve integrated PC and HF services. Data from both WPs will be analysed and synthesised using a realist logic of analysis. WP3 will facilitate the development of a community of practice to support those who wish to set up, sustain and embed integrated PC and HF services.

Discussion: This realist evaluation of a complex intervention will improve understanding of how to tailor and implement integrated PC and HF services. The co-designed 'how-to guide' and community of practice will facilitate knowledge translation and ensure that evidence-based guidance is provided to assist in service development.

Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis, often diagnosed at an advanced stage. Chromosomal instability (CIN), a hallmark of cancer, leads to the release of cytosolic double-stranded DNA (dsDNA), which activates the cGAS-STING pathway and its downstream immune signaling. However, the prognostic implications of this pathway in CCA remain poorly understood. This study aims to examine the cGAS-STING pathway-related proteins in CCA and their correlation with clinicopathological parameters. A total of 164 formalin-fixed paraffin-embedded (FFPE) CCA tissue samples were analyzed using tissue microarray (TMA) and immunohistochemistry (IHC). Statistical analysis assessed correlations between proteins expression and clinicopathological features were assessed using Chi-square tests, logistic regression, Kaplan-Meier survival analysis, Cox proportional hazards models, and Spearman's rank correlation coefficient. Moderate-to-high STING expression was significantly associated with reduced tumor size and lymphovascular invasion but paradoxically correlated with short overall survival (p < 0.05). In contrast, moderate-to-high γH2AX expression predicted improved survival. IRF3 expression was significantly higher in the tubular histological subtype of CCA compared to the papillary subtype (p = 0.012), indicating a possible morphological correlation. Multivariate analysis confirmed STING as an independent prognostic marker for CCA. Our findings suggest that STING appears to function as a double-edged sword in CCA, limiting local invasion while paradoxically contributing to poor survival outcomes. IRF3 expression appears linked to histological subtypes, supporting its role in tumor biology. These markers may provide valuable insights into tumor behavior and may guide treatment strategies in CCA patients.