bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smoking status and clinical outcome in idiopathic pulmonary fibrosis: a nationwide study
Authors: Yoon Hee-Young , Kim Hoseob , Bae Yoonjong , Song Jin Woo 
Published: April 2024

Abstract
Background
Smoking status has been linked to the development of idiopathic pulmonary fibrosis (IPF). However, the effect of smoking on the prognosis of patients with IPF is unclear. We aimed to investigate the association between smoking status and all-cause mortality or hospitalisation by using national health claims data.

Methods
IPF cases were defined as people who visited medical institutions between January 2002 and December 2018 with IPF and rare incurable disease exempted calculation codes from the National Health Insurance Database. Total 10,182 patients with available data on smoking status were included in this study. Ever-smoking status was assigned to individuals with a history of smoking ≥ 6 pack-years. The multivariable Cox proportional hazard model was used to evaluate the association between smoking status and prognosis.

Results
In the entire cohort, the mean age was 69.4 years, 73.9% were males, and 45.2% were ever smokers (current smokers: 14.2%; former smokers: 31.0%). Current smokers (hazard ratio [HR]: 0.709; 95% confidence interval [CI]: 0.643–0.782) and former smokers (HR: 0.926; 95% CI: 0.862–0.996) were independently associated with all-cause mortality compared with non-smokers. Current smokers (HR: 0.884; 95% CI: 0.827–0.945) and former smokers (HR: 0.909; 95% CI: 0.862–0.959) were also associated with a reduced risk of all-cause hospitalisation compared with non-smokers. A non-linear association between smoking amount and prognosis was found in a spline HR curve and showed increasing risk below 6 pack-years.

Conclusion
Ever-smoking status may be associated with favourable clinical outcomes in patients with IPF.
Association of the triglyceride-glucose index with early-onset atherosclerotic cardiovascular disease events and all-cause mortality: a prospective cohort study
Authors: Hou Qiqi , Qi Qi , Han Quanle , Yu Jie , Wu Jianmei , Yang Hui , Chen Shuohua , Wu Shouling , Li Kangbo 
Published: April 2024

Abstract
Background
The association between the triglyceride glucose (TyG) index and the risk of early-onset atherosclerotic cardiovascular disease (ASCVD) events or all-cause mortality in young and middle-aged people is not fully elucidated.

Methods
The present study included 64,489 young and middle-aged people who participated in the 2006 Kailuan Study physical examination. Multivariate Cox proportional hazards models and restricted cubic spline curves were used to assess the association of TyG index with early-onset ASCVD events and all-cause mortality.

Results
During a median of 11-year follow-up, 1984 (3.08%) participants experienced at least one ASCVD event and 1,392 (2.16%) participants experienced all-cause death. A higher TyG index was significantly associated with a higher risk of early-onset ASCVD events (HR: 1.61, 95% CI 1.38–1.89) and all-cause mortality (HR: 1.39, 95% CI 1.17–1.65), respectively. For each unit increase in TyG index, the risk of early-onset ASCVD events increased by 20%. In addition, there was a non-linear association between the TyG index and early-onset ASCVD events (P for non-linear < 0.01), and a linear association between TyG index and all-cause mortality (P for non-linear = 0.476).

Conclusions
A higher TyG index is significantly associated with an increased incidence of early-onset ASCVD events and all-cause mortality in a young and middle-aged population from North China.
Therapeutic efficacy of generic artemether–lumefantrine in the treatment of uncomplicated malaria in Ghana: assessing anti-malarial efficacy amidst pharmacogenetic variations
Authors: Thomford Nicholas Ekow , Kellermann Tracy , Biney Robert Peter , Dixon Charné , Nyarko Samuel Badu , Ateko Richmond Owusu , Ekor Martins , Kyei George B. 
Published: April 2024

Abstract
Background
Despite efforts made to reduce morbidity and mortality associated with malaria, especially in sub-Saharan Africa, malaria continues to be a public health concern that requires innovative efforts to reach the WHO-set zero malaria agenda. Among the innovations is the use of artemisinin-based combination therapy (ACT) that is effective against Plasmodium falciparum. Generic artemether–lumefantrine (AL) is used to treat uncomplicated malaria after appropriate diagnosis. AL is metabolized by the cytochrome P450 family of enzymes, such as CYP2B6, CYP3A4 and CYP3A5, which can be under pharmacogenetic influence. Pharmacogenetics affecting AL metabolism, significantly influence the overall anti-malarial activity leading to variable therapeutic efficacy. This study focused on generic AL drugs used in malarial treatment as prescribed at health facilities and evaluated pharmacogenomic influences on their efficacy.

Methods
Patients who have been diagnosed with malaria and confirmed through RDT and microscopy were recruited in this study. Blood samples were taken on days 1, 2, 3 and 7 for parasite count and blood levels of lumefantrine, artemisinin, desbutyl-lumefantrine (DBL), and dihydroartemisinin (DHA), the active metabolites of lumefantrine and artemether, respectively, were analysed using established methods. Pharmacogene variation analysis was undertaken using iPLEX microarray and PCR–RFLP.

Results
A total of 52 patients completed the study. Median parasite density from day 1 to 7 ranged from 0–2666/μL of blood, with days 3 and 7 recording 0 parasite density. Highest median plasma concentration for lumefantrine and desbutyl lumefantrine, which are the long-acting components of artemisinin-based combinations, was 4123.75 ng/mL and 35.87 ng/mL, respectively. Day 7 plasma lumefantrine concentration across all generic ACT brands was ≥ 200 ng/mL which potentially accounted for the parasitaemia profile observed. Monomorphism was observed for CYP3A4 variants, while there were observed variations in CYP2B6 and CYP3A5 alleles. Among the CYP3A5 genotypes, significant differences in genotypes and plasma concentration for DBL were seen on day 3 between 1/*1 versus *1/*6 (p = 0.002), *1/*3 versus *1/*6 (p = 0.006) and *1/*7 versus *1/*6 (p = 0.008). Day 7 plasma DBL concentrations showed a significant difference between *1/*6 and *1/*3 (p = 0.026) expressors.

Conclusions
The study findings show that CYP2B6 and CYP3A5 pharmacogenetic variations may lead to higher plasma exposure of AL metabolites.
Cholesterol mediates the effects of single and multiple environmental phenols in urine on obesity
Authors: Yu Ting , Zhang Yuqing , Yuan Jiali , Zhang Yue , Li Jing , Huang Zhenyao 
Published: April 2024

Abstract
Background
Overweight and obesity are among the leading chronic diseases worldwide. Environmental phenols have been renowned as endocrine disruptors that contribute to weight changes; however, the effects of exposure to mixed phenols on obesity are not well established.

Methods
Using data from adults in National Health and Nutrition Examination Survey, this study examined the individual and combined effects of four phenols on obesity. A combination of traditional logistic regression and two mixed models (weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR)) were used together to assess the role of phenols in the development of obesity. The potential mediation of cholesterol on these effects was analyzed through a parallel mediation model.

Results
The results demonstrated that solitary phenols except triclosan were inversely associated with obesity (P-value < 0.05). The WQS index was also negatively correlated with general obesity (β: 0.770, 95% CI: 0.644–0.919, P-value = 0.004) and abdominal obesity (β: 0.781, 95% CI: 0.658–0.928, P-value = 0.004). Consistently, the BKMR model demonstrated the significant joint negative effects of phenols on obesity. The parallel mediation analysis revealed that high-density lipoprotein mediated the effects of all four single phenols on obesity, whereas low-density lipoprotein only mediated the association between benzophenol-3 and obesity. Moreover, Cholesterol acts as a mediator of the association between mixed phenols and obesity. Exposure to single and mixed phenols significantly and negatively correlated with obesity. Cholesterol mediated the association of single and mixed environmental phenols with obesity.

Conclusions
Assessing the potential public health risks of mixed phenols helps to incorporate this information into practical health advice and guidance.
Adapting the EQ-5D-3L for adults with mild to moderate learning disabilities
Authors: O’Dwyer John L. , Bryant Louise D. , Hulme Claire , Kind Paul , Meads David M. 
Published: April 2024

Abstract
Background
Approximately 1.5 million adults in the UK have a learning disability. The difference between age at death for this group and the general population is 26 years for females and 22 years for males. The NHS Long Term Plan (January 2019) recognises learning disabilities as a clinical priority area. People with a learning disability are often excluded from research by design or lack of reasonable adjustments, and self-reported health status/health-related quality of life questionnaires such as the EQ-5D are often not appropriate for this population. Here, we systematically examine the EQ-5D-3L (its wording, content, and format) using qualitative methods to inform the adaption of the measure for use with adults with mild to moderate learning disabilities.

Methods
Think-aloud interviews with carers/advocates of learning-disabled adults were undertaken to explore the difficulties with completing the EQ-5D-3L. Alternative wording, language, structure, and images were developed using focus groups, stakeholder reference groups, and an expert panel. Data analysis followed a framework method.

Results
The dimensions and levels within the EQ-5D-3L were deemed appropriate for adults with mild to moderate learning disabilities. Consensus on wording, structure, and images was reached through an iterative process, and an adapted version of the EQ-5D-3L was finalised.

Conclusion
The EQ-5D-3L adapted for adults with mild to moderate intellectual/learning disabilities can facilitate measurement of self-reported health status. Research is underway to assess the potential use of the adaptation for economic evaluation.
Early career researchers in health policy and systems research: insights from freelancers in a non-profit organization in the Philippines
Authors: Sales Reneepearl Kim , Navarro Marion Abilene 
Published: April 2024

Abstract
Background
The freelance economy has seen rapid growth worldwide in recent years and the Philippines is not an exception. Freelance workers are becoming increasingly common in healthcare and research. Early career researchers carry out most of scientific research and can play a critical role in advancing public health by bringing new perspectives and diversity to the field. Existing literature has mostly focused on the experiences of early career researchers in an institutional academic setting. This study aimed to understand the experiences of freelance early career researchers in the health policy and systems space in the Philippines.

Methods
This qualitative study collected data from 18 to 22 March 2022 through virtual interview and focus group discussions. Themes and codes were created based on the topic guide developed. New themes and codes were generated as they emerged. Two researchers coded the data using both a priori and emergent codes. Any coding conflicts were resolved through discussions until intercoder agreement was reached. Interpretation and conclusions from the data were developed by 2 researchers with consideration for its context and relationship between themes.

Results
Fifteen current and former freelance researchers participated in the study. Most are female, under 35 years old, and with an undergraduate degree as the highest educational attainment. The findings highlight insights and challenges faced by early career researchers in aspects of: (1) work arrangement, (2) tasks, (3) expectations from senior researchers, (4) development in the health policy and systems field, (5) relationship with peers, and (6) motivations for continuing to work as a freelance health policy and systems researcher.

Conclusion
This study reveals the challenges freelance early career researchers face, highlighting the need for enhanced support and recognition amidst rapidly evolving workforce demands and complex health dilemmas. Recommendations include structured mentorship, professional development, innovative funding models, and the establishment of a supportive network. Advocacy for policies ensuring freelancer inclusion in the economy and policy-making is crucial. Future research should investigate their experiences further, including their roles, transitions, and the impacts of funding trends, to foster their development and integration into public health research and policy.
What is context in knowledge translation? Results of a systematic scoping review
Authors: Schmitt Tugce , Czabanowska Katarzyna , Schröder-Bäck Peter 
Published: April 2024

AbstractKnowledge Translation (KT) aims to convey novel ideas to relevant stakeholders, motivating their response or action to improve people’s health. Initially, the KT literature focused on evidence-based medicine, applying findings from laboratory and clinical research to disease diagnosis and treatment. Since the early 2000s, the scope of KT has expanded to include decision-making with health policy implications.This systematic scoping review aims to assess the evolving knowledge-to-policy concepts, that is, macro-level KT theories, models and frameworks (KT TMFs). While significant attention has been devoted to transferring knowledge to healthcare settings (i.e. implementing health policies, programmes or measures at the meso-level), the definition of 'context' in the realm of health policymaking at the macro-level remains underexplored in the KT literature. This study aims to close the gap.A total of 32 macro-level KT TMFs were identified, with only a limited subset of them offering detailed insights into contextual factors that matter in health policymaking. Notably, the majority of these studies prompt policy changes in low- and middle-income countries and received support from international organisations, the European Union, development agencies or philanthropic entities.
Was it a HIIT? A process evaluation of a school-based high-intensity interval training intervention
Authors: Duncombe Stephanie L. , Barker Alan R. , Price Lisa , Walker Jacqueline L. , Koep Jodie L. , Woodforde James , Stylianou Michalis 
Published: April 2024

Abstract
Background
Despite a growing body of research investigating high-intensity interval training (HIIT) in schools, there are limited process evaluations investigating their implementation. This is concerning because process evaluations are important for appropriately interpreting outcome findings and augmenting intervention design. This manuscript presents a process evaluation of Making a HIIT, a school-based HIIT intervention.

Methods
The Making a HIIT intervention spanned 8 weeks and was completed at three schools in Greater Brisbane, Australia. Ten classes (intervention group) completed 10-min teacher-led HIIT workouts at the beginning of health and physical education (HPE) lessons, and five classes (control group) continued with regular HPE lessons. The mixed methods evaluation was guided by the Framework for Effective Implementation by Durlak and DuPre.

Results
Program reach: Ten schools were contacted to successfully recruit three schools, from which 79% of eligible students (n = 308, $$\overline{{\text{x}} }$$

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age: 13.0 ± 0.6 years, 148 girls) provided consent. Dosage: The average number of HIIT workouts provided was 10 ± 3 and the average number attended by students was 6 ± 2. Fidelity: During HIIT workouts, the percentage of time students spent at ≥ 80% of maximum heart rate (HRmax) was 55% (interquartile range (IQR): 29%—76%). Monitoring of the control group: During lessons, the intervention and control groups spent 32% (IQR: 12%—54%) and 28% (IQR: 13%—46%) of their HPE lesson at ≥ 80% of HRmax, respectively. Responsiveness: On average, students rated their enjoyment of HIIT workouts as 3.3 ± 1.1 (neutral) on a 5-point scale. Quality: Teachers found the HIIT workouts simple to implement but provided insights into the time implications of integrating them into their lessons; elements that helped facilitate their implementation; and their use within the classroom. Differentiation: Making a HIIT involved students and teachers in the co-design of HIIT workouts. Adaption: Workouts were modified due to location and weather, the complexity of exercises, and time constraints.

Conclusion
The comprehensive evaluation of Making a HIIT provides important insights into the implementation of school-based HIIT, including encouragings findings for student enjoyment and fidelity and recommendations for improving dosage that should be considered when developing future interventions.

Trial Registration
ACTRN, ACTRN12622000534785, Registered 5 April 2022 – Retrospectively registered.
Large-scale genome-wide association studies reveal the genetic causal etiology between air pollutants and autoimmune diseases
Authors: Wen Jie , Zhang Jingwei , Zhang Hao , Zhang Nan , Lei Ruoyan , Deng Yujia , Cheng Quan , Li He , Luo Peng 
Published: April 2024

Abstract
Background
Epidemiological evidence links a close correlation between long-term exposure to air pollutants and autoimmune diseases, while the causality remained unknown.

Methods
Two-sample Mendelian randomization (TSMR) was used to investigate the role of PM10, PM2.5, NO2, and NOX (N = 423,796–456,380) in 15 autoimmune diseases (N = 14,890–314,995) using data from large European GWASs including UKB, FINNGEN, IMSGC, and IPSCSG. Multivariable Mendelian randomization (MVMR) was conducted to investigate the direct effect of each air pollutant and the mediating role of common factors, including body mass index (BMI), alcohol consumption, smoking status, and household income. Transcriptome-wide association studies (TWAS), two-step MR, and colocalization analyses were performed to explore underlying mechanisms between air pollution and autoimmune diseases.

Results
In TSMR, after correction of multiple testing, hypothyroidism was causally associated with higher exposure to NO2 [odds ratio (OR): 1.37, p = 9.08 × 10–4] and NOX [OR: 1.34, p = 2.86 × 10–3], ulcerative colitis (UC) was causally associated with higher exposure to NOX [OR: 2.24, p = 1.23 × 10–2] and PM2.5 [OR: 2.60, p = 5.96 × 10–3], rheumatoid arthritis was causally associated with higher exposure to NOX [OR: 1.72, p = 1.50 × 10–2], systemic lupus erythematosus was causally associated with higher exposure to NOX [OR: 4.92, p = 6.89 × 10–3], celiac disease was causally associated with lower exposure to NOX [OR: 0.14, p = 6.74 × 10–4] and PM2.5 [OR: 0.17, p = 3.18 × 10–3]. The risky effects of PM2.5 on UC remained significant in MVMR analyses after adjusting for other air pollutants. MVMR revealed several common mediators between air pollutants and autoimmune diseases. Transcriptional analysis identified specific gene transcripts and pathways interconnecting air pollutants and autoimmune diseases. Two-step MR revealed that POR, HSPA1B, and BRD2 might mediate from air pollutants to autoimmune diseases. POR pQTL (rs59882870, PPH4=1.00) strongly colocalized with autoimmune diseases.

Conclusion
This research underscores the necessity of rigorous air pollutant surveillance within public health studies to curb the prevalence of autoimmune diseases.

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Changes in blood metabolomes as potential markers for severity and prognosis in doxorubicin-induced cardiotoxicity: a study in HER2-positive and HER2-negative breast cancer patients
Authors: Thonusin Chanisa , Osataphan Nichanan , Leemasawat Krit , Nawara Wichwara , Sriwichaiin Sirawit , Supakham Siriporn , Gunaparn Siriluck , Apaijai Nattayaporn , Somwangprasert Areewan , Phrommintikul Arintaya , Chattipakorn Siriporn C. , Chattipakorn Nipon 
Published: April 2024

Abstract
Background
We aimed to compare the changes in blood metabolomes and cardiac parameters following doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients. Additionally, the potential roles of changes in blood metabolomes as severity and prognostic markers of doxorubicin-induced cardiotoxicity were determined.

Methods
HER2-positive (n = 37) and HER2-negative (n = 37) breast cancer patients were enrolled. Cardiac function assessment and blood collection were performed at baseline and 2 weeks after completion of doxorubicin treatment in all patients, as well as at three months after completion of doxorubicin treatment in HER2-negative breast cancer patients. Blood obtained at all three-time points was processed for measuring cardiac injury biomarkers. Blood obtained at baseline and 2 weeks after completion of doxorubicin treatment were also processed for measuring systemic oxidative stress and 85 metabolome levels.

Results
Cardiac injury and systolic dysfunction 2 weeks after completion of doxorubicin treatment were comparable between these two groups of patients. However, only HER2-negative breast cancer patients exhibited increased systemic oxidative stress and cardiac autonomic dysfunction at this time point. Moreover, 33 and 29 blood metabolomes were altered at 2 weeks after completion of doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients, respectively. The changes in most of these metabolomes were correlated with the changes in cardiac parameters, both at 2 weeks and 3 months after completion of doxorubicin treatment.

Conclusions
The changes in blood metabolomes following doxorubicin treatment were dependent on HER2 status, and these changes might serve as severity and prognostic markers of doxorubicin-induced cardiotoxicity.
Trial registration: The study was conducted under ethical approval from the Institutional Review Board of the Faculty of Medicine, Chiang Mai University (Registration number: MED-2563-07001; Date: April 28, 2020). The study also complied with the Declaration of Helsinki.