bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic antibiotics for Pseudomonas aeruginosa infection in outpatients with non-hospitalised exacerbations of pre-existing lung diseases: a randomised clinical trial
Authors: Eklöf Josefin , Alispahic Imane Achir , Armbruster Karin , Lapperre Therese Sophie , Browatzki Andrea , Overgaard Rikke Holmen , Harboe Zitta Barrella , Janner Julie , Moberg Mia , Ulrik Charlotte Suppli , Andreassen Helle Frost , Weinreich Ulla Møller , Kjærgaard Jakob Lyngby , Villadsen Jenny , Fenlev Camilla Sund , Jensen Torben Tranborg , Christensen Christina Wellendorph , Bangsborg Jette , Ostergaard Christian , Ghathian Khaled Saoud Ali , Jordan Alexander , Klausen Tobias Wirenfeldt , Nielsen Thyge Lynghøj , Wilcke Torgny , Seersholm Niels , Sivapalan Pradeesh , Jensen Jens-Ulrik Stæhr 
Published: June 2024

Abstract
Background
The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes.

Methods
Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365.

Results
The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27–0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6–1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3–4.5) in the control group, p = 0.037.

Conclusions
Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial.

Trial Registration
ClinicalTrials.gov, NCT03262142, registration date 2017–08-25.
LLIN Evaluation in Uganda Project (LLINEUP): modelling the impact of COVID-19-related disruptions on delivery of long-lasting insecticidal nets on malaria indicators in Uganda
Authors: Okiring Jaffer , Gonahasa Samuel , Maiteki-Sebuguzi Catherine , Katureebe Agaba , Bagala Irene , Mutungi Peter , Kigozi Simon P. , Namuganga Jane F. , Nankabirwa Joaniter I. , Kamya Moses R. , Donnelly Martin J. , Churcher Thomas S. , Staedke Sarah G. , Sherrard-Smith Ellie 
Published: June 2024

Abstract
Background
Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3–4 years, but the 2020–2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme.

Methods
A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020–2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020–2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017–2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations.

Results
Approximately 70% of the study population received LLINs later than scheduled in 2020–2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected.

Conclusions
The model results suggest that the disruptions in the 2020–2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas.
Association of longitudinal pet ownership with wheezing in 3-year-old children using the distributed lag model: the Japan Environment and Children’s Study
Authors: Shirato Kota , Oba Koji , Matsuyama Yutaka , Hagiwara Yasuhiro ,   The Japan Environment and Children’s Study (JECS) Group
Published: June 2024

Abstract
Background
Time-varying exposures like pet ownership pose challenges for identifying critical windows due to multicollinearity when modeled simultaneously. The Distributed Lag Model (DLM) estimates critical windows for time-varying exposures, which are mainly continuous variables. However, applying complex functions such as high-order splines and nonlinear functions within DLMs may not be suitable for situations with limited time points or binary exposure, such as in questionnaire surveys.

Objectives
(1) We examined the estimation performance of a simple DLM with fractional polynomial function for time-varying binary exposures through simulation experiments. (2) We evaluated the impact of pet ownership on childhood wheezing onset and estimate critical windows.

Methods
(1) We compared logistic regression including time-varying exposure in separate models, in one model simultaneously, and using DLM. For evaluation, we employed bias, empirical standard error (EmpSE), and mean squared error (MSE). (2) The Japan Environment and Children's Study (JECS) is a prospective birth cohort study of approximately 100,000 parent-child pairs, registered across Japan from 2011 to 2014. We applied DLM to the JECS data up to age 3. The estimated odds ratios (OR) were considered to be within critical windows when they were significant at the 5% level.

Results
(1) DLM and the separate model exhibited lower bias compared to the simultaneously model. Additionally, both DLM and the simultaneously model demonstrated lower EmpSEs than the separate model. In all scenarios, DLM had lower MSEs than the other methods. Specifically, where critical windows is clearly present and exposure correlation is high, DLM showed MSEs about 1/2 to 1/200 of those of other models. (2) Application of DLM to the JECS data showed that, unlike other models, a significant exposure effect was observed only between the ages of 0 and 6 months. During that periods, the highest ORs were 1.07 (95% confidence interval, 1.01 to 1.14) , observed between the ages of 2 and 5 months.

Conclusions
(1) A simple DLM improves the accuracy of exposure effect and critical windows estimation. (2) 0–6 months may be the critical windows for the effect of pet ownership on the wheezing onset at 3 years.
Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics
Authors: Yang Song , Sun Yiran , Yan Chenchen 
Published: June 2024

AbstractAdipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs are also capable of promoting tissue regeneration through the secretion of various cytokines, factors, and extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate a range of biomolecules. These EVs have been found to mediate the therapeutic activities of donor cells by promoting the proliferation and migration of effector cells, facilitating angiogenesis, modulating immunity, and performing other specific functions in different tissues. Compared to the donor cells themselves, ADSC-EVs offer advantages such as fewer safety concerns and more convenient transportation and storage for clinical application. As a result, these EVs have received significant attention as cell-free therapeutic agents with potential future application in regenerative medicine. In this review, we focus on recent research progress regarding regenerative medical use of ADSC-EVs across various medical conditions, including wound healing, chronic limb ischemia, angiogenesis, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage regeneration, tendinopathy and tendon healing, peripheral nerve regeneration, and acute lung injury, among others. We also discuss the underlying mechanisms responsible for inducing these therapeutic effects. We believe that deciphering the biological properties, therapeutic effects, and underlying mechanisms associated with ADSC-EVs will provide a foundation for developing a novel therapeutic approach in regenerative medicine.
Graphical Abstract
Role of mesenchymal stem cell-derived exosomes in the regeneration of different tissues
Authors: Huang Defa , Shen Haibin , Xie Fangfang , Hu Die , Jin Qing , Hu Yuexin , Zhong Tianyu 
Published: June 2024

AbstractExosomes are nanovesicles with multiple components used in several applications. Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. MSC-derived exosomes (MSC-Exos) have been shown to mediate tissue regeneration in various diseases, including neurological, autoimmune, and inflammatory diseases, cancer, ischemic heart disease, lung injury, and liver fibrosis. They can modulate the immune response by interacting with immune effector cells in the presence of anti-inflammatory compounds and are involved in intercellular communication through various types of cargo. This review summarizes the MSC-Exos-mediated tissue regeneration in various diseases, including neurological, cardiovascular, liver, kidney, articular cartilage, and oral tissue applications. In addition, we discuss the challenges and prospects of MSC-Exos in tissue regeneration.
Hypoxia and re-oxygenation effects on human cardiomyocytes cultured on polycaprolactone and polyurethane nanofibrous mats
Authors: Iwoń Zuzanna , Krogulec Ewelina , Kierlańczyk Aleksandra , Wojasiński Michał , Jastrzębska Elżbieta 
Published: June 2024

AbstractHeart diseases are caused mainly by chronic oxygen insufficiency (hypoxia), leading to damage and apoptosis of cardiomyocytes. Research into the regeneration of a damaged human heart is limited due to the lack of cellular models that mimic damaged cardiac tissue. Based on the literature, nanofibrous mats affect the cardiomyocyte morphology and stimulate the growth and differentiation of cells cultured on them; therefore, nanofibrous materials can support the production of in vitro models that faithfully mimic the 3D structure of human cardiac tissue. Nanofibrous mats were used as scaffolds for adult primary human cardiomyocytes (HCM) and immature human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). This work focuses on understanding the effects of hypoxia and re-oxygenation on human cardiac cells cultured on polymer nanofibrous mats made of poly(ε-caprolactone) (PCL) and polyurethane (PU). The expression of selected genes and proteins in cardiomyocytes during hypoxia and re-oxygenation were evaluated. In addition, the type of cell death was analyzed. To the best of our knowledge, there are no studies on the effects of hypoxia on cardiomyocyte cells cultured on nanofibrous mats. The present study aimed to use nanofiber mats as scaffolds that structurally could mimic cardiac extracellular matrix. Understanding the impact of 3D structural properties in vitro cardiac models on different human cardiomyocytes is crucial for advancing cardiac tissue engineering and regenerative medicine. Observing how 3D scaffolds affect cardiomyocyte function under hypoxic conditions is necessary to understand the functioning of the entire human heart.
NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation
Authors: Zhang Xuran , An Ke , Ge Xin , Sun Yuanyuan , Wei Jingyao , Ren Weihong , Wang Han , Wang Yueqin , Du Yue , He Lulu , Li Ouwen , Zhou Shaoxuan , Shi Yong , Ren Tong , Yang Yun-gui , Kan Quancheng , Tian Xin 
Published: June 2024

Abstract
Background
RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC.

Methods
Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC.

Results
As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells.

Conclusions
This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.
DNA methylation patterns of transcription factor binding regions characterize their functional and evolutionary contexts
Authors: Rimoldi Martina , Wang Ning , Zhang Jilin , Villar Diego , Odom Duncan T. , Taipale Jussi , Flicek Paul , Roller Maša 
Published: June 2024

Abstract
Background
DNA methylation is an important epigenetic modification which has numerous roles in modulating genome function. Its levels are spatially correlated across the genome, typically high in repressed regions but low in transcription factor (TF) binding sites and active regulatory regions. However, the mechanisms establishing genome-wide and TF binding site methylation patterns are still unclear.

Results
Here we use a comparative approach to investigate the association of DNA methylation to TF binding evolution in mammals. Specifically, we experimentally profile DNA methylation and combine this with published occupancy profiles of five distinct TFs (CTCF, CEBPA, HNF4A, ONECUT1, FOXA1) in the liver of five mammalian species (human, macaque, mouse, rat, dog). TF binding sites are lowly methylated, but they often also have intermediate methylation levels. Furthermore, biding sites are influenced by the methylation status of CpGs in their wider binding regions even when CpGs are absent from the core binding motif. Employing a classification and clustering approach, we extract distinct and species-conserved patterns of DNA methylation levels at TF binding regions. CEBPA, HNF4A, ONECUT1, and FOXA1 share the same methylation patterns, while CTCF's differ. These patterns characterize alternative functions and chromatin landscapes of TF-bound regions. Leveraging our phylogenetic framework, we find DNA methylation gain upon evolutionary loss of TF occupancy, indicating coordinated evolution. Furthermore, each methylation pattern has its own evolutionary trajectory reflecting its genomic contexts.

Conclusions
Our epigenomic analyses indicate a role for DNA methylation in TF binding changes across species including that specific DNA methylation profiles characterize TF binding and are associated with their regulatory activity, chromatin contexts, and evolutionary trajectories.
The impact of inactivity during the COVID-19 pandemic on the physical performance of high school athletes
Authors: Asan Selim , Ulupınar Süleyman , Özbay Serhat , Namlı Sevinç , Gençoğlu Cebrail , Canyurt Ferhat , Çingöz Yunus Emre , Özkara Abdullah Bora 
Published: June 2024

Abstract
Background/Objective
This study was conducted during the 2019–2020 academic year to evaluate the impact of participation in school sports on students’ Body Mass Index (BMI) and Assessing Levels of Physical Activity (ALPHA) test scores. Interrupted by the COVID-19 pandemic, which led to a suspension of in-person education, the study resumed in September 2021, refocusing on the effects of pandemic-induced inactivity on the physical fitness levels of the same cohort.

Methods
The study included twenty-nine male high school students (age: 17,24 ± 0,73 years), divided into thirteen athletes (participating in sports such as football, basketball, and track) and sixteen non-athletic counterparts. They underwent reassessment using the ALPHA test battery, evaluating cardiorespiratory, musculoskeletal, and motor skills fitness. Data were analyzed using independent and paired samples t-tests and a two-way repeated measures ANOVA to assess changes over time and between groups. Discriminant function analysis evaluated the ALPHA test’s ability to classify students based on their athletic status pre- and post-pandemic.

Results
Initially, athlete students exhibited significantly better BMI, 20 m shuttle run, and 4 × 10 m speed run scores compared to their non-athlete peers. After the pandemic, only the 20 m shuttle run scores remained significantly higher for athletes, with diminished distinctions in other fitness areas. The classification accuracy of the ALPHA test battery decreased from 89.7 to 75.9% post-pandemic.

Conclusion
The enforced sedentary lifestyle due to the COVID-19 pandemic adversely affected all students, particularly diminishing health-related fitness parameters such as body composition, cardiorespiratory and musculoskeletal strength, and motor skills. Students previously engaged in regular physical activity, notably school athletes, experienced significant fitness declines. This highlights the urgent need for targeted interventions to encourage active lifestyles among youth in the post-pandemic phase, aiming to avert long-term adverse health outcomes.
On the fractional perturbed neutral integro-differential systems via deformable derivatives: an existence study
Authors: Sreedharan R. , Balachandar S. Raja , Udhayakumar R. , Etemad Sina , Avcı İbrahim , Rezapour Shahram 
Published: June 2024

AbstractIn this paper, we provide some appropriate conditions for the existence of solutions for a perturbed fractional neutral integro-differential system under the deformable derivative in a Banach space. Using the Banach contraction principle and Krasnoselskii’s fixed point theorem, we establish some new existence theorems. Moreover, we provide two numerical examples to demonstrate the applicability of the theoretical results
The inflationary effect of the budget deficit: does financial sector development matter?
Authors: Aragaw Abebe 
Published: June 2024

AbstractThis study aims to examine the budget deficit–inflation relationship, considering financial sector development and broad money supply as moderating and mediating variables. For this purpose, a panel data set ranging from polled mean group, mean group, and dynamic fixed effect estimation techniques are employed. Hence, the pooled mean group estimation result reveals that the budget deficit is inflationary. In addition, GDP per capita, the effective exchange rate, financial sector development, regulatory quality, and the interaction term of the budget deficit and financial sector development are significant determinants of inflation. The study further examines the role of the broad money supply as a mediating variable in the budget deficit–inflation relationship. The structural equation model results and the mediation effect tests confirmed a partial mediation effect of the broad money supply on the budget deficit–inflation relationship. Based on the findings, it is recommended to strengthen regulatory quality, reduce broad money supply, and improve financial sector development. By doing so, we can create a more stable and efficient economy that benefits everyone in the long run.