bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of pulse wave analysis under reactive hyperemia and close to an arteriovenous fistula: a comparative analysis
Authors: Busch Veit , Müller Sandra , Streis Joachim , Westhoff Timm H. , Felderhoff Thomas , Seibert Felix S. , Reuter Stefan , Mueller Niklas 
Published: February 2025

Abstract

Background
Analyzing novel pulse wave parameters, we aimed to study specific changes in pulse waveform under high flow conditions in three collectives (i.e., healthy individuals and two collectives of patients with kidney disease and different levels of comorbidities): First, under reactive hyperemia in order to assess endothelial function. Second, close to an ateriovenous fistula in order to assess fistula function.

Methods
Subjects underwent local peripheral tonometric pulse wave analysis with the SphygmoCor® device and duplex sonography to assess flow velocity (peak Vmax and diastolic Vdiast) under physiological conditions. Corresponding measurements were then performed under reactive hyperemia and at fistula arms. The area under the curve and the mean slope between the systolic peak and the end of systole of pulse waves and duplex flow velocities were analysed as parameter differences under high flow and physiological conditions (∆A2 and ∆m2, ∆Vmax and ∆Vdiast). In addition, the augmentation index was evaluated (only) under physiological conditions. The Wilcoxon test was used to assess parameter differences and linear correlation was performed.

Results
A total of 108 subjects were evaluated (23 healthy and 85 with fistula in two distinct collectives n = 39/45, measurements under reactive hyperemia in 62 individuals). Significant increments in the novel pulse parameters were observed under reactive hyperemia and near a fistula and were found to correlate with corresponding changes in flow velocity (reactive hyperemia: ∆A2 and ∆m2/Vmax r = 0.347, p = 0.006 and r = 0.374, p = 0.003; fistula: ∆A2/∆Vmax r = 0.315, p = 0.003, no significant correlation for ∆m2/Vmax). Consistent with their different vascular status and endothelial function, changes in pulse wave parameters during reactive hyperemia were significantly different in patients and healthy subjects. Both high flow conditions induced similar changes in the pulse waveform and a delay of the systolic peak in all three collectives. The augmentation index was different in the three collectives and correlated with the increase of the novel parameters and the peak flow velocity under reactive hyperemia: ∆A2 r = 0.445, p < 0.001, ∆m2 r = 0.338, p = 0.007, ∆Vmax r = 0.460.

Conclusion
Detection of changes in pulse waveform under high flow conditions is potentially a new clinical application to characterize endothelial function and the functional status of ateriovenous fistulas.
Regional differences in triage decisions affect hospital mortality among frail COVID-19 patients in the COvid MEdicaTion study
Authors: Minnema Julia , Sablerolles Roos , van Kempen Janneke , van der Kuy Hugo , Polinder-Bos Harmke , van de Loo Bob , Versmissen Jorie , Haaksma Miriam L. , Lafeber Melvin , Faes Miriam C. ,   on behalf of the COMET research team^
Published: February 2025

Abstract

Objectives
The scarcity of intensive care unit (ICU) beds during the COVID-19 pandemic has led to a large number of national and international guidelines for the triage of ICU admission. Regional variation in medical decision making might affect ICU triage decisions. We investigate whether regional differences in ICU admission, as surrogate for triage decisions, affect in-hospital mortality in COVID-19 patients.

Methods
The COMET study is a multicenter, observational cohort study, including adult patients hospitalized for COVID-19 between March 2020– July 2020. Patients’ characteristics, prescribed medication, clinical characteristics, and CFS were collected. Patients from 11 European countries were included and these countries were categorized into two regions: north and south. The effects of region on ICU admission and in-hospital mortality were assessed using logistic regression analyses stratified for frailty.

Results
Frail patients had a higher risk for ICU admission in southern compared to northern countries (OR: 1.64; 95%CI: 1.10–2.46), whereas fit patients had a similar risk for ICU admission in southern compared to northern countries (OR: 0.75; 95%CI: 0.55–1.01). There was no difference in in-hospital mortality between northern and southern countries for fit and frail patients (respectively OR: 0.82; 95% CI 0.52–1.29, and OR: 1.11; 95% CI: 0.74–1.66).

Conclusion
Our study shows that, despite variation in rates of ICU admission between northern and southern countries for frail patients, no difference in in-hospital mortality was observed. This might help optimize prioritization of resources in a pandemic setting while offering options for palliative care instead of ICU admission.
Assessment of sleep problems in patients with Kawasaki disease: a survey-based study
Authors: Tharwat Samar , Nassar Mohammed Kamal 
Published: February 2025

Abstract

Introduction
Kawasaki disease (KD) is a rare systemic inflammatory disease that primarily affects children under the age of five. It is now recognized as the most prevalent cause of acquired heart diseases in children in developed countries.

Objectives
The aim of this study was to evaluate sleep disturbances in patients with KD and identify their prevalence and associations.

Methods
This cross-sectional analytic survey-based study was carried out on 262 participants (130 KD patients and 132 age- and sex-matched healthy controls). Participants were invited via social media groups. Sociodemographic data, clinical characteristics and therapeutic data of KD patients were collected. To identify the presence of sleep disturbances, all participants completed Children’s Sleep Habits Questionnaire (CSHQ).

Results
The median age for KD patients was 6 years, and 51.5% of them were female, the median age at disease onset was 2.5 years, and the median disease duration was 3 years. The sleep scores of patients with KD were significantly higher than those of the control group (55.72 ± 11.97 vs. 49.45 ± 8.54, p < 0.001). The total duration of sleep did not exhibit any statistically significant difference between patients with KD and healthy controls (p = 0.399). KD patients exhibited significantly elevated scores in sleep onset delay, sleep duration, night wakings, parasomnias, and sleep-disordered breathing (p < 0.001). Additionally, they showed marginally higher scores in daytime sleepiness (p = 0.059). Younger age of KD patients was associated with higher rates of bedtime resistance (p < 0.001) and sleep anxiety (p = 0.005). Younger age at KD onset was associated significantly with higher rates of bedtime resistance (p = 0.009), sleep anxiety (p = 0.038), night wakings (p = 0.017), and worse sleep quality (p = 0.033). KD Patients who exhibited lethargy, and received corticosteroid medication had significantly higher sleep scores than those who did not.

Conclusion
Patients with KD experience higher sleep disturbance than their healthy counterparts. Young age, early disease onset, lethargy and corticosteroid administration are linked to poor sleep quality.
Barriers and facilitators to detection and treatment of obstructive sleep apnoea syndrome in people with severe mental illnesses, qualitative interview study and referrer survey
Authors: Faulkner Sophie , Firth Joseph , Shiers David , Kalucy Megan 
Published: February 2025

Abstract
Obstructive sleep apnoea syndrome (OSAS) is a relatively common condition. It has a range of negative health and quality of life implications, but there are established tests to detect it, and recommended treatment pathways which have been well tested. OSAS is prevalent in people with severe mental illness (SMI), and research suggests it is under-detected in this group. This study aimed to examine and explore barriers and facilitators to the detection and treatment of OSAS in people with severe mental illnesses. Staff and patients with a range of relevant experiences were interviewed, and a large scale survey of potential OSAS referrers was conducted. Interviews were analysed thematically, survey responses were summarised descriptively, and results are presented together for comparison and enhanced interpretation. The results highlight a lack of awareness of OSAS outside of specialist sleep services, resulting in poor detection and treatment of OSAS in people with SMI. Comorbidities, symptoms and circumstances of this group may make the presence of OSAS less obvious, and can make diagnosis and adapting to treatment more difficult, but also emphasise the benefits of successful continuous positive airway pressure (CPAP) treatment in this group. The challenges of adapting to CPAP were described and acknowledged, but the impact of successful CPAP was for some life changing. The harm of delayed diagnosis was perceived as unjust. We recommend increased screening for OSAS in people with SMI, supported by increased education and training about OSAS in staff who work with people with severe mental illnesses, and increased awareness in service users and carers.
Single-nucleotide polymorphisms in dizygotic twin ovine fetuses are associated with discordant responses to antenatal steroid therapy
Authors: Fee Erin L. , Usuda Haruo , Carter Sean W. D. , Ikeda Hideyuki , Takahashi Tsukasa , Takahashi Yuki , Kumagai Yusaku , Clarke Michael W. , Ireland Demelza J. , Newnham John P. , Saito Masatoshi , Illanes Sebastian E. , Sesurajan Binny Priya , Shen Liang , Choolani Mahesh A. , Oguz Gokce , Ramasamy Adaikalavan , Ritchie Sara , Ritchie Andrew , Jobe Alan H. , Kemp Matthew W. 
Published: February 2025

Abstract

Background
Antenatal steroid (ANS) therapy is given to women at risk of preterm delivery to accelerate fetal lung maturation. However, the benefit of ANS therapy is variable and how maternal and fetal factors contribute to this observed variability is unknown. We aimed to test the degree of concordance in preterm lung function, and correlate this with genomic, transcriptomic, and pharmacokinetic variables in preterm dizygotic twin ovine fetuses.

Methods
Thirty-one date-mated ewes carrying twin fetuses at 123 ± 1 days’ gestation received maternal intramuscular injections of either (i) 1 × 0.25 mg/kg betamethasone phosphate and acetate (CS1, n = 11 twin pairs) or (ii) 2 × 0.25 mg/kg betamethasone phosphate and acetate, 24 h apart (CS2, n = 10 twin pairs) or (iii) 2 × saline, 24 h apart (negative control, n = 10 twin pairs). Fetuses were surgically delivered 24 h after their final treatment and ventilated for 30 min.

Results
ANS-exposed female fetuses had lower arterial partial pressure of carbon dioxide (PaCO2) values than male fetuses (76.5 ± 38.0 vs. 97.2 ± 42.5 mmHg), although the observed difference was not statistically significant (p = 0.1). Only 52% of ANS-treated twins were concordant for lung maturation responses. There was no difference in fetal lung tissue or plasma steroid concentrations within or between twin pairs. Genomic analysis identified 13 single-nucleotide polymorphisms (SNPs) statistically associated with ANS-responsiveness, including in the proto-oncogene MET and the transcription activator STAT1.

Conclusions
Twin fetal responses and ANS tissue levels were comparable with those from singleton fetuses in earlier studies. Twin ovine fetuses thus benefit from ANS in a similar manner to singleton fetuses, and a larger dose of betamethasone is not required. Assuming no difference in input from the placental or maternal compartments, fetal lung responses to ANS therapy in dizygotic twin preterm lambs are dependent on the fetus itself. These data suggest a potential heritable role in determining ANS responsiveness.
The Data Artifacts Glossary: a community-based repository for bias on health datasets
Authors: Gameiro Rodrigo R. , Woite Naira Link , Sauer Christopher M. , Hao Sicheng , Fernandes Chrystinne Oliveira , Premo Anna E. , Teixeira Alice Rangel , Resli Isabelle , Wong An-Kwok Ian , Celi Leo Anthony 
Published: February 2025

Abstract

Background
The deployment of Artificial Intelligence (AI) in healthcare has the potential to transform patient care through improved diagnostics, personalized treatment plans, and more efficient resource management. However, the effectiveness and fairness of AI are critically dependent on the data it learns from. Biased datasets can lead to AI outputs that perpetuate disparities, particularly affecting social minorities and marginalized groups.

Objective
This paper introduces the “Data Artifacts Glossary”, a dynamic, open-source framework designed to systematically document and update potential biases in healthcare datasets. The aim is to provide a comprehensive tool that enhances the transparency and accuracy of AI applications in healthcare and contributes to understanding and addressing health inequities.

Methods
Utilizing a methodology inspired by the Delphi method, a diverse team of experts conducted iterative rounds of discussions and literature reviews. The team synthesized insights to develop a comprehensive list of bias categories and designed the glossary’s structure. The Data Artifacts Glossary was piloted using the MIMIC-IV dataset to validate its utility and structure.

Results
The Data Artifacts Glossary adopts a collaborative approach modeled on successful open-source projects like Linux and Python. Hosted on GitHub, it utilizes robust version control and collaborative features, allowing stakeholders from diverse backgrounds to contribute. Through a rigorous peer review process managed by community members, the glossary ensures the continual refinement and accuracy of its contents. The implementation of the Data Artifacts Glossary with the MIMIC-IV dataset illustrates its utility. It categorizes biases, and facilitates their identification and understanding.

Conclusion
The Data Artifacts Glossary serves as a vital resource for enhancing the integrity of AI applications in healthcare by providing a mechanism to recognize and mitigate dataset biases before they impact AI outputs. It not only aids in avoiding bias in model development but also contributes to understanding and addressing the root causes of health disparities.
Antimicrobial and antiproliferative activity of biosynthesized manganese nanocomposite with amide derivative originated by endophytic Aspergillus terreus
Authors: El-Gazzar Nashwa , Farouk Reem , Diab Nervana S. , Rabie Gamal , Sitohy Basel 
Published: February 2025

Abstract

Background
Scientists have faced difficulties in synthesizing natural substances with potent biological activity from cost-effective sources. Endophytic fungi metabolites with nanoparticles have been utilized to develop a friendly, suitable procedure to address this problem and ameliorate the average amount of antioxidant, antimicrobial, and anticancer materials. Therefore, this study utilized endophytic fungi as a source of the natural extract with biosynthesized manganese nanoparticles (MnNPs) in the form of nanocomposites.

Methods
Thirty endophytic fungi were isolated and were assessed for their antioxidant activity by 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) and antimicrobial activity. The most potent isolate was identified utilizing 18S rRNA and was applied to purify and separate their natural antimicrobial products by Flash column chromatography. In addition, the most potent product was identified based on instrumental analysis through Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), and Gas chromatography-mass spectrometry (GC.MS). The purified product was combined with biosynthsesized manganese nanoparticles (MnNPs) for the production of nanocomposite (MnNCs). Later on, the physicochemical features of MnNPs and its MnNCs were examined and then they were assessed for determination their biological activities.

Results
The most potent isolate was identified as Aspergillus terreus with accession number OR243300. The antioxidant and antimicrobial product produced by the strain A. terreus was identified as an amide derivative consisting of 3-(2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-4-oxopentanoic acid (HDOCOX) with the chemical formula C13H18O5. Furthermore, purified HDOCOX, MnNPs and Mn-HDOCOX-NPs nanocomposite (MnNCs) showed significant antimicrobial effectiveness. The minimum inhibitory concentrations (MICs) determined for MnNCs were 10 µg/mL against C. albicans and E.coli. Furthermore, MnNCs were reduced hepatocellular carcinoma viability.

Conclusion
The use of HDOCOX, either alone or in combination with MnNPs, is a potential candidate for inhibiting pathogenic microbes and the development of an anticancer drug pipeline.
Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine
Authors: Zhao Yongqiang , Liu Jia , Peng Chun , Guo Shuangshuang , Wang Bo , Chen Longping , Wang Yating , Tang Haiwen , Liu Liming , Pan Qi , Li Shiren , Wang Jingyu , Yang Dongni , Du Enqi 
Published: February 2025

Abstract

Background
Influenza A viruses (IAVs) cause seasonal influenza epidemics and pose significant threats to public health. However, seasonal influenza vaccines often elicit strain-specific immune responses and confer little protection against mismatched strains. There is an urgent need to develop universal influenza vaccines against emerging and potentially re-emerging influenza virus infections. Multiepitope vaccines combining multiple conserved epitopes can induce more robust and broader immune responses and provide a potential solution.

Results
Here, we demonstrated that an HA chimeric multiepitope nanoparticle vaccine, delivered intranasally conferred broad protection against challenges with various influenza viruses in mice. The nanoparticle vaccine co-expresses the ectodomain of haemagglutinin (H), three repeated highly conserved ectodomains of matrix protein 2 (M), and the M-cell-targeting ligand Co4B (C) in a baculovirus-insect cell system. These elements (C, H and M) were presented on the surface of self-assembling ferritin (f) in tandem to generate a nanoparticle denoted as CHM-f. Intranasal vaccination with CHM-f nanoparticles elicited robust humoral and cellular immune responses, conferring complete protection against a variety of IAVs, including the A/PR8/34 H1N1 strain, the swine flu H3N2 strain, the avian flu H5N8 strain, and H9N2. When CHM-f nanoparticles adjuvanted with CpG IAMA-002, the weight loss protective effect, cellular immune responses and mucosal IgA responses were significantly augmented. Compared with controls, mice immunized with CHM-f nanoparticles with or without CpG IAMA-002 showed significant reductions in weight loss, lung viral titres and pathological changes.

Conclusions
These results suggest that CHM-f nanoparticle with or without CpG IAMA-002 is a promising candidate as a universal influenza vaccine.

Graphical Abstract
“Lost in translation?” Animal research in the era of precision medicine
Authors: Frühwein Hamideh , Paul Norbert W. 
Published: February 2025

Abstract
Preclinical animal research has long been a cornerstone in evaluating the efficacy, toxicity, and safety of potential drug treatments before they proceed to human clinical trials. However, given the intricate nature of human physiology and the complexities of diseases such as cancer, this paper critically examines the role of animal experimentation in translational research, both from epistemological and ethical viewpoints. We argue that the ethical obligation to protect animals extends beyond their instrumental value for human benefit; it is rooted in the intrinsic value of their well-being. Consequently, we advocate for a paradigm shift in medical research: the adoption of new approach methodologies (NAMs) not merely as supplementary tools but as complete replacements for animal use in medical studies. In this context, replacement emerges as the key principle—an imperative that should be prioritized over all other considerations.
A missense variant in the SOX5 gene (c.221C > T) is associated with intellectual disability
Authors: Yang Xiujuan , Gan Zhongzhi , Guo Xiaoling , Huang Xiang , Liu Juan , Zheng Yingchun , Zhou Xiaoqiang , Lian Jingli , Liu Yue , Yang Tingting , Li Chao , Chen Fenying , He Fei , Xu Xiangmin , Zhou Yasi , Liu Qian , Yang Xingkun , Xiong Fu 
Published: February 2025

Abstract

Objectives
The SOX5 gene has been identified as the pathogenic gene responsible for Lamb-Shaffer syndrome. In this study, we examined the SOX5 variant (c.221C > T, p.Thr74Met) within a Chinese family presenting with intellectual disability and evaluated the functional implications of SOX5 by in vitro experiment.

Materials and methods
The family underwent a clinical assessment of intellectual development, which included precise clinical exome sequencing to identify causative genetic variants. The potential deleterious effects and pathogenicity of the variant were predicted using bioinformatics tools such as Mutation Taster, PROVEAN, and SIFT. Additionally, protein stability was evaluated using I-Mutant, and 3D protein structures were modeled with I-TASSER. Western blots and QPCR were employed to assess gene expression and protein stability. Flow cytometry was utilized to compare the cell cycle dynamics between wild-type and mutant cells.

Results
A previously identified missense variant (c.221C > T) in the SOX5 gene was determined to be the underlying cause of intellectual disability in a Chinese family. Functional assays demonstrated that mutant cells exhibited increased levels of SOX5 mRNA and protein relative to wild-type cells, accompanied by enhanced protein stability. Additionally, the mutant SOX5 protein was found to alter the cell cycle and downregulate the mRNA expression levels of the ACAN, AXIN2, SOX9, and PDGFRA genes.

Conclusions
We confirmed that the SOX5 p.Thr74Met variant is associated with intellectual disability in a second-generation Chinese family. This mutant protein potentially exhibits increased stability, influences the cell cycle, and downregulates genes related to bone and neural functions.