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☐ ☆ ✇ PLOS ONE Medicine&Health

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: 
☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Lei Xiong · Ke Li · Wendy Siuyi Wong — Diciembre 15th 2025 at 15:00

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.

☐ ☆ ✇ PLOS ONE Medicine&Health

<i>Mycobacterium tuberculosis</i> 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 
☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Mi Lv · Hui Che · Jiayan Hu · Wenxi Yu · Zhaoxia Liu · Xiaolin Zhou · Binduo Zhou · Jinyi Xie · Fengyun Wang — Diciembre 15th 2025 at 15:00

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 P 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.

☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Hellen W. Kinyi · Charles Kato Drago · Lucy Ochola · Gertrude N. Kiwanuka — Diciembre 15th 2025 at 15:00

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 
☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Yinli Shi · Shuang Guan · Sicun Wang · Muzhi Li · Yanan Yu · Jun Liu · Weibin Yang · Zhong Wang — Diciembre 15th 2025 at 15:00

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.

☐ ☆ ✇ PLOS ONE Medicine&Health

Health risk realization versus warning: Impact on lifestyle behaviours

Por: Zoey Verdun — Diciembre 15th 2025 at 15:00

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.
☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Ying Li · Jing Jia · Runze Lu · Liyan Dong · Lizhu Fang · Litao Sun · Zongyi Zhang · Qing Duan · Lijie Zhang · Kunzheng Lv · Huilai Ma — Diciembre 15th 2025 at 15:00

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.

☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Zihang Zhao · Xiang Zhang · Xi Hou · Zihan Liu · Zhiyong Hou · Lianxin Song · Ruipeng Zhang — Diciembre 15th 2025 at 15:00

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 
☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Qian Yue Tan · Kinda Ibrahim · Helen C. Roberts · Khaled Amar · Simon D.S. Fraser — Diciembre 15th 2025 at 15:00

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.

☐ ☆ ✇ PLOS ONE Medicine&Health

Development of a competition assay to assess the <i>in vitro</i> 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.

☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Nikola Lübbering · Alexander Krogmann · Felix Jansen · Eicke Latz · Georg Nickenig · Sebastian Zimmer — Diciembre 15th 2025 at 15:00

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 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.

☐ ☆ ✇ PLOS ONE Medicine&Health

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.

☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Zhongqun Guo · Qiangqiang Liu · Feiyue Luo · Shaojun Xie · Tianhua Zhou — Diciembre 15th 2025 at 15:00

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.
☐ ☆ ✇ PLOS ONE Medicine&Health

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

Por: Marie Chantel Montás · Chimezie Anyakora · Elisa Maria Maffioli — Diciembre 15th 2025 at 15:00

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.
☐ ☆ ✇ PLOS ONE Medicine&Health

Perspective of healthcare professionals on barriers and facilitators in exploring end-of-life care preferences of patients with pulmonary fibrosis: A qualitative study

Por: Lian Trapman · Lea M Dijksman · Jan C. Grutters · Saskia C.C.M. Teunissen · Everlien de Graaf — Diciembre 12th 2025 at 15:00

by Lian Trapman, Lea M Dijksman, Jan C. Grutters, Saskia C.C.M. Teunissen, Everlien de Graaf

Background

Progressive pulmonary fibrosis is a lethal disease with a survival of 3–5 years with optimal medication treatment. Palliative care and advance care planning are therefore receiving increasing attention in the literature. However, structural implementation in clinical practice is still lacking. The aim of this study was to explore the needs, facilitators, and barriers for communication on the topic of end-of-life preferences of patients from the perspective of healthcare professionals.

Methods

A generic qualitative study was performed with focus groups and individual semi structured interviews with healthcare professionals. Data collection and analysis were performed iteratively. A thematic analysis was performed, following the methods of Braun and Clarke.

Results

Three focus groups and seven individual semi-structured interviews were conducted. Three themes were generated: (1) a lack of vision on palliative care, resulting in different approaches within the same clinic and showing the need for optimization of collaboration; (2) the importance of a learning-driven environment to support healthcare professionals skills and knowledge; and (3), the central role of the individual professional in developing skills and knowledge.

Conclusions/discussion

This study underscores the importance of behavioral and organizational change in palliative care to optimize conversations exploring values, preferences, and needs for end-of-life care for patients with pulmonary fibrosis. Leveraging the shared motivation of healthcare professionals to provide optimal care, integrating these findings into training and coaching programs can further enhance patient-centered approach in palliative care.

☐ ☆ ✇ PLOS ONE Medicine&Health

Coping with rejection as a sperm donor: A qualitative study of the personal impact of rejection and new health information

Por: Lina Thirup · Anne-Bine Skytte · Ulrik Schiøler Kesmodel · Ida Vogel · Guido Pennings · Allan Pacey · Stina Lou — Diciembre 12th 2025 at 15:00

by Lina Thirup, Anne-Bine Skytte, Ulrik Schiøler Kesmodel, Ida Vogel, Guido Pennings, Allan Pacey, Stina Lou

Purpose

The demand for sperm donation is increasing, yet only a small percentage of applicants are accepted, and little attention has been given to those who are rejected. The application process may reveal new medical or genetic information with potential personal and emotional consequences. The aim of this study was to explore how men experience rejection as sperm donors, including how they cope with the rejection and integrate potential new information into their lives.

Methods

We conducted qualitative, in-depth interviews with 19 men rejected as sperm donors. Data was analyzed using thematic analysis.

Results

Some men received new medical information that raised significant concerns, particularly regarding their health, fertility, and family. However, for most it was not the reason for rejection that affected them most, but the rejection itself. They had begun to identify as donors, and being turned down felt like a blow to their sense of self. Over time, participants used different coping strategies: information seeking, actionable reasoning, positive reframing, normalizing, and postponing. Although the experience was personally and emotionally challenging for many, it ultimately did not have a lasting negative impact on their lives.

Conclusions

Sperm donation is not only a medical act but also tied to social identity, with rejection having personal and emotional consequences. For men whose rejection is based on new medical information that causes significant concerns, sperm banks should support rejected donors and help them exit the process positively. Further research is warranted to find out how this can be done.

☐ ☆ ✇ PLOS ONE Medicine&Health

Machine learning-guided identification and simulation-based validation of potent JAK3 inhibitors for cancer therapy

Por: Hailang Wei · Qingyun Wang — Diciembre 12th 2025 at 15:00

by Hailang Wei, Qingyun Wang

Janus kinase 3 (JAK3) is a hematopoietic-specific kinase implicated in cytokine signaling and immune dysregulation and has recently been associated with cancer progression. However, selective and potent JAK3 inhibitors remain underdeveloped. In this study, we established a machine learning (ML)-based pipeline to identify novel JAK3 inhibitors with anti-cancer potential. A curated ChEMBL dataset of JAK3 inhibitors was used to train multiple ML classifiers, with the Random Forest model achieving the highest performance (AUC = 0.80, F1-score = 0.92). This model was applied to virtually screen 25,084 ChEMBL compounds, yielding 400 high-confidence candidates (prediction score > 0.9). Docking analysis identified ten top binders (binding affinity ≤ –8.5 kcal/mol), of which three CHEMBL49087, CHEMBL4117527, and CHEMBL50064 exhibited optimal ADMET profiles. These compounds underwent 200 ns molecular dynamics simulations, showing low RMSD (0.10–0.20 nm), stable binding conformations, and preserved protein compactness. MM/GBSA calculations revealed that CHEMBL4117527 displayed the strongest binding free energy (–29.5 kcal/mol), surpassing even the co-crystallized ligand (–17.7 kcal/mol). Our integrative approach combining machine learning, docking, pharmacokinetics, molecular dynamics, and free energy analysis presents a robust computational strategy for JAK3 inhibitor discovery. These findings support CHEMBL4117527 as promising candidates for further experimental evaluation in cancer therapeutics.
☐ ☆ ✇ PLOS ONE Medicine&Health

Efficacy of imaginative vocal training for enhancing vocal awareness in non-professional singers

Por: Federica Biassoni · Giulia Vismara · Martina Gnerre — Diciembre 12th 2025 at 15:00

by Federica Biassoni, Giulia Vismara, Martina Gnerre

The objective of this study was to examine whether different types of mental-imagery training focused on the vocal apparatus can enhance awareness of the vocal tract and diaphragm (vocal awareness) in non-professional singers.Sixty participants with no singing education received one of three training conditions: following instructions based on 1) a description of the physiological changes that take place during phonation (physiological description), 2) imitating an action using the vocal apparatus (imitative action), and 3) a metaphorical narration. Imitative action and metaphorical narration were conceptualized as more imaginative forms of training. Vocal awareness was assessed with a questionnaire that participants completed before and after the training. The questionnaire measured three indices: vocal apparatus representation, vocal apparatus interoceptive awareness, and vocal self-regulation. Results showed that all three types of training program significantly enhanced vocal awareness, but imitative action and metaphorical narration were more effective for interoceptive awareness, and metaphorical narration was more effective for self-regulation. In conclusion, the two imaginative forms of training were more effective than physiological description for improving vocal awareness.
☐ ☆ ✇ PLOS ONE Medicine&Health

Drug-related stigma among people who inject drugs – development and validation of the drug use stigma scale (DUSS)

Por: Robin A. Pollini · Catherine E. Paquette · Brandon Irvin · Jennifer L. Syvertsen · Christa L. Lilly — Diciembre 12th 2025 at 15:00

by Robin A. Pollini, Catherine E. Paquette, Brandon Irvin, Jennifer L. Syvertsen, Christa L. Lilly

Drug use is a highly stigmatized behavior, and drug-related stigma is a key driver of behavioral risk, lower health care utilization, and associated adverse health outcomes among people who inject drugs (PWID). While instruments exist for measuring drug-related stigma, their applicability to community-based PWID across multiple stigma types (enacted, anticipated, internalized) and settings (health care, society, family) is limited, as most were developed using treatment-based samples and all were developed in urban populations. This study sought to develop a Drug Use Stigma Scale (DUSS) that addresses these limitations. We developed an initial list of 39 items based on literature review and qualitative interviews (N = 27) and three focus groups (N = 28) with PWID recruited from syringe services programs and via peer referral in two predominantly rural West Virginia counties. The scale items were administered in a survey to 336 PWID recruited from the same two counties divided into development and validation samples. Responses to the 39-item scale went through a multidimensional refinement process, including examination of internal consistency, Confirmatory Factor Analysis (CFA), and a three-factor CFA based on stigma setting. Next, a set of final measurement CFAs were conducted. Finally, the resulting scale was examined for criterion-related concurrent validation. The final DUSS consisted of 16 items with excellent fit statistics for the development sample: SRMR: 0.03, RMSEA: 0.09, GFI: 0.92, CFI: 0.96, NFI: 0.94. Fit attenuated but remained satisfactory for the validation sample. DUSS scores were significantly associated with increased odds of not seeking healthcare when needed (OR: 1.47, p = 0.001; OR: 1.61, p 
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